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A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Participants (MOMENTUM)

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ClinicalTrials.gov Identifier: NCT04173494
Recruitment Status : Completed
First Posted : November 22, 2019
Results First Posted : December 22, 2022
Last Update Posted : November 1, 2023
Sponsor:
Information provided by (Responsible Party):
Sierra Oncology LLC - a GSK company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Primary Myelofibrosis
Post-polycythemia Vera Myelofibrosis
Post-essential Thrombocythemia Myelofibrosis
Interventions Drug: Momelotinib
Drug: Placebo to match danazol
Drug: Danazol
Drug: Placebo to match momelotinib
Enrollment 195
Recruitment Details This study evaluated the activity of Momelotinib (MMB) versus Danazol (DAN) in Symptomatic, Anemic participants. This study consists of Randomized Double-blind (DB) Treatment Period (TP) and Open-label extended Treatment Period.
Pre-assignment Details A total of 195 participants were enrolled in the study.
Arm/Group Title MMB 200 mg Once Daily (QD) + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period. Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 enrolled in an open-label extended treatment period. Participants switched to receive 200 mg of MMB orally QD during open-label extended treatment period. All participants elected to receive MMB as open-label treatment during the open-label extended treatment period.
Period Title: Randomized DB TP (Up to Week 24)
Started 130 65
Completed 94 38
Not Completed 36 27
Reason Not Completed
Adverse Event             16             11
Withdrawal by Subject             6             5
Lack of Efficacy             6             3
Death             4             3
Leukemic Transformation             2             2
Disease Progression             1             2
Lost to Follow-up             1             0
Physician Decision             0             1
Period Title: Open-Label Extended TP(Weeks 24 to 151)
Started 93 [1] 41 [2]
Completed 0 0
Not Completed 93 41
Reason Not Completed
Adverse Event             11             1
Death             6             3
Lack of Efficacy             6             2
Physician Decision             4             3
Withdrawal by Subject             4             3
Leukemic transformation             0             1
Disease progression             1             1
Continuing in MMB extension study             61             27
[1]
93 participants from Randomized Treatment Phase entered in Open-label Phase
[2]
Total 41 participants entered in Open-label Phase (36 out of 38 participants who completed Randomized Phase and 5 out of 27 who withdrew from Randomized Phase) as per Protocol defined criteria.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo Total
Hide Arm/Group Description Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period. Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period. Total of all reporting groups
Overall Number of Baseline Participants 130 65 195
Hide Baseline Analysis Population Description
Baseline characteristics were measured in the Intention-To-Treat (ITT) Analysis Set, which included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 130 participants 65 participants 195 participants
69.85  (8.24) 71.46  (6.99) 70.38  (7.86)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 65 participants 195 participants
Female
51
  39.2%
21
  32.3%
72
  36.9%
Male
79
  60.8%
44
  67.7%
123
  63.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 65 participants 195 participants
Hispanic or Latino
5
   3.8%
6
   9.2%
11
   5.6%
Not Hispanic or Latino
115
  88.5%
54
  83.1%
169
  86.7%
Unknown or Not Reported
10
   7.7%
5
   7.7%
15
   7.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 130 participants 65 participants 195 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
12
   9.2%
6
   9.2%
18
   9.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
   1.5%
2
   3.1%
4
   2.1%
White
107
  82.3%
50
  76.9%
157
  80.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
9
   6.9%
7
  10.8%
16
   8.2%
1.Primary Outcome
Title Total Symptom Score (TSS) Response Rate at Week 24
Hide Description Myelofibrosis Symptom Assessment Form (MFSAF) TSS version (v) 4.0 response rate was defined as percentage of participants with a >= 50 percent (%) reduction from Baseline in mean MFSAF TSS over consecutive 28-day period immediately before end of Week 24. TSS response rate was measured using MFSAF v4.0. MFSAF v4.0 comprises 7 domains representing 7 most relevant symptoms of myelofibrosis (MF) identified through existing participant and clinician-based evidence: fatigue,night sweats,pruritus,abdominal discomfort,pain under left ribs,early satietyand bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0(absent) to 10(worst imaginable). The MFSAF TSS was calculated as sum of scores of 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Measured in the Intent-To-Treat (ITT) Analysis Set, which included all randomized participants.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
24.62
(17.49 to 32.94)
9.23
(3.46 to 19.02)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0095
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Cochran-Mantel-Haenszel
Estimated Value 15.67
Confidence Interval (2-Sided) 95%
5.54 to 25.81
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants With Transfusion Independence (TI) at Week 24
Hide Description TI status was defined as not receiving red blood cell (RBC) or whole blood transfusion for >=12 weeks, with no hemoglobin (Hgb) level < 8 grams per deciliter (g/dL) during the same interval. Percentage of participants with TI have been presented.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
30.0
(22.28 to 38.66)
20.00
(11.10 to 31.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments If the lower bound of the confidence interval (CI) is greater than 0, MMB was to be declared non-inferior to DAN.
Statistical Test of Hypothesis P-Value 0.0116
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Non-inferiority difference
Estimated Value 13.58
Confidence Interval (2-Sided) 95%
1.86 to 25.30
Estimation Comments Non-inferiority difference, defined as p(MMB) - (0.8) *p(DAN) where p(MMB) is percentage of participants with TI status in MMB arm and p(DAN) is percentage of participants with TI status in DAN arm.
3.Secondary Outcome
Title Splenic Response Rate (SRR) of >=25% at Week 24
Hide Description Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of >=25% from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
39.23
(30.79 to 48.18)
6.15
(1.70 to 15.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Cochran-Mantel-Haenszel
Estimated Value 33.05
Confidence Interval (2-Sided) 95%
22.59 to 43.51
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in MFSAF TSS at Week 24
Hide Description TSS was measured using the MFSAF v4.0. The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). The MFSAF TSS was calculated as the sum of scores of the 7 domains for a possible range of scores of 0 to 70, with a higher TSS corresponding to more severe symptoms. A reduction from Baseline corresponded to a lessening of MF symptoms. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Only those participants with data available at specified time points were analyzed.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 92 37
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-9.36  (1.08) -3.13  (1.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0014
Comments [Not Specified]
Method mixed model for repeated measures (MMRM)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -6.22
Confidence Interval (2-Sided) 95%
-10.0 to -2.43
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Splenic Response Rate (SRR) of >= 35% at Week 24
Hide Description Splenic response rate (SRR) is defined as the percentage of participants who have reduction in spleen volume of >=35 % from Baseline at the end of Week 24. Baseline was the last assessment done before or on the day of first dose date.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
22.31
(15.48 to 30.44)
3.08
(0.37 to 10.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Cochran-Mantel-Haenszel
Estimated Value 18.18
Confidence Interval (2-Sided) 95%
9.77 to 26.59
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Zero RBC Units Transfused Over 24-Weeks
Hide Description Percentage of participants with zero RBC units transfused over 24-weeks were reported.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
35.38
(27.20 to 44.25)
16.92
(8.76 to 28.27)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Cochran-Mantel-Haenszel
Estimated Value 17.20
Confidence Interval (2-Sided) 95%
7.99 to 26.40
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With <=4 RBC Units Transfused Over 24-weeks
Hide Description Percentage of participants with <=4 RBC units transfused over 24-weeks were reported.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
55.38
(46.42 to 64.10)
44.62
(32.27 to 57.47)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1133
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified Cochran-Mantel-Haenszel
Estimated Value 10.62
Confidence Interval (2-Sided) 95%
-2.40 to 23.64
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Duration of MFSAF TSS Response
Hide Description Duration of MFSAF TSS response is defined as the number of days from the start of the initial 28-day period in which a participant had a >= 50% reduction from Baseline TSS to the first day of the 7-day assessment that determines the mean TSS for the 28-day period during which the participants TSS equals or exceeds their Baseline value.
Time Frame Up to a maximum of 151 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Only those participants with data available at specified time point were analyzed.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 32 6
Median (Inter-Quartile Range)
Unit of Measure: Days
286.00
(286.00 to 286.00)
NA [1] 
(NA to NA)
[1]
<25% of participants experienced the event within the treatment arm. Hence, median and inter-quartile range could not be derived.
9.Secondary Outcome
Title Duration of TI Response
Hide Description Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level < 8 g/dL (except in the case of clinically overt bleeding).
Time Frame Up to a maximum of 151 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Only those participants with data available at specified time point were analyzed.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 39 13
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
<25% of participants experienced the event within the treatment arm. Hence, median and inter-quartile range could not be derived.
10.Secondary Outcome
Title Mean Cumulative Number of Whole Blood Units Transfused Over 24 Weeks
Hide Description Cumulative transfusion risk was calculated as the estimated mean cumulative number of whole blood units transfused during the study.
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Mean (Standard Deviation)
Unit of Measure: Whole blood units
6.55  (8.413) 10.86  (13.203)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0006
Comments [Not Specified]
Method Anderson & Gill proportional means model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.556
Confidence Interval (2-Sided) 95%
0.397 to 0.778
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Percentage of Participants With Transfusion Dependence (TD) Status at Week 24
Hide Description TD status at Week 24 is defined as requirement of >=4 RBC units in an 8-week period immediately prior to the end of Week 24.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
15.38
(9.66 to 22.76)
24.62
(14.77 to 36.87)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1602
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified CMH
Estimated Value -8.26
Confidence Interval (2-Sided) 95%
-20.18 to 3.66
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With a Hemoglobin Response
Hide Description Hemoglobin responses are defined as increases of >= 1, >= 1.5, or >= 2 g/dL from Baseline in Hgb, as measured over a (rolling) period of at least 12 consecutive weeks falling entirely before the end of Week 24. Baseline was the last assessment done before or on the day of first dose date. Data has been reported for percentage of participants who had >= 1, >= 1.5, or >= 2 g/dL increase from Baseline in hemoglobin.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
>=1g/dL Increase
53.08
(44.13 to 61.88)
33.85
(22.57 to 46.65)
>=1.5g/dL Increase
40.00
(31.51 to 48.95)
23.08
(13.53 to 35.19)
>=2g/dL Increase
29.23
(21.59 to 37.85)
20.00
(11.10 to 31.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0124
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified CMH
Estimated Value 19.00
Confidence Interval (2-Sided) 95%
4.68 to 33.32
Estimation Comments >=1g/dL Increase in Hemoglobin response
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0282
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified CMH
Estimated Value 15.68
Confidence Interval (2-Sided) 95%
2.47 to 28.90
Estimation Comments >=1.5g/dL Increase in Hemoglobin response
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2844
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Stratified CMH
Estimated Value 6.97
Confidence Interval (2-Sided) 95%
-5.41 to 19.35
Estimation Comments >=2g/dL Increase in Hemoglobin response
13.Secondary Outcome
Title Number of Baseline TD Participants With TI Status at Week 24
Hide Description Participants were defined as having TD if they met both of the following requirements in the 8 weeks immediately before the end of Week 24: >= 4 red blood cell or whole blood units were transfused (except in the case of clinically overt bleeding), each in response to a hemoglobin assessment of <= 9.5 g/dL; and there were >= 2 hemoglobin assessments with >= 28 days between the earliest and latest hemoglobin assessments. TI status was defined as not requiring red blood cell transfusion (except in the case of clinically overt bleeding) for >= 12 weeks immediately prior to the end of Week 24, with hemoglobin levels >= 8 g/dL.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Only those participants with data available at specified time points were analyzed.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 63 34
Measure Type: Count of Participants
Unit of Measure: Participants
9
  14.3%
3
   8.8%
14.Secondary Outcome
Title Duration of TI in Baseline TD Participants
Hide Description Duration of TI is defined as the number of days from (a) the first day of a 12-week period that satisfies the 12-week TI status definition, to (b) the first RBC transfusion or Hgb level < 8 g/dL (except in the case of clinically overt bleeding).
Time Frame Up to a maximum of 151 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Only those participants with data available at specified time points were analyzed.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 63 34
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(224.0 to NA)
NA [2] 
(196.0 to NA)
[1]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived
[2]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
15.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- up to Week 24
Hide Description An adverse event (AE) is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants in the ITT Analysis set who received at least one dose of study drug.
Arm/Group Title MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period
Hide Arm/Group Description:
Participants were randomized to receive 200 mg of MMB orally QD and a DAN-placebo orally BID during the randomized 24-week double-blind treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period.
Overall Number of Participants Analyzed 130 65
Measure Type: Count of Participants
Unit of Measure: Participants
Any non-SAEs
108
  83.1%
55
  84.6%
Any SAEs
45
  34.6%
26
  40.0%
16.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)- From Week 24 to a Maximum of 151 Weeks
Hide Description An AE is any untoward medical occurrence in a trial participant administered an investigational product(s), a comparator product, or an approved drug regardless of the causal relationship with treatment. An SAE is an AE that Results in death, life threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital anomaly/birth defect or any important medical events as per medical or scientific judgment. Adverse events which were not Serious were considered as Non-Serious adverse events.
Time Frame From Week 24 to a maximum of 151 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title MMB 200 mg QD- Open-Label Extended Treatment Period DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period
Hide Arm/Group Description:
Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period.
Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 93 41
Measure Type: Count of Participants
Unit of Measure: Participants
Any non-SAEs
57
  61.3%
28
  68.3%
Any SAEs
30
  32.3%
12
  29.3%
17.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall survival is defined as the interval from the first study drug dosing date (or randomization date for participants who did not receive treatment) to death from any cause.
Time Frame Up to a maximum of 151 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Values are presented based on the Kaplan-Meier analysis. All participants (overall population) were included in analysis.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Median (Inter-Quartile Range)
Unit of Measure: Days
624.0 [1] 
(333.0 to NA)
NA [2] 
(309.00 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
[2]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6879
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.890
Confidence Interval (2-Sided) 95%
0.504 to 1.572
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Leukemia-free Survival (LFS)
Hide Description LFS is defined as the interval from first study drug dosing date (or randomization date for participants who did not receive treatment) to any evidence of leukemic transformation and/or death (from any cause).
Time Frame Up to a maximum of 151 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Values are presented based on the Kaplan-Meier analysis. All participants (overall population) were included in analysis.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 130 65
Median (Inter-Quartile Range)
Unit of Measure: Days
624.0 [1] 
(325.0 to NA)
NA [2] 
(284.0 to NA)
[1]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived
[2]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4320
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.804
Confidence Interval (2-Sided) 95%
0.466 to 1.386
Estimation Comments [Not Specified]
19.Secondary Outcome
Title Change From Baseline in Disease-related Fatigue as Assessed by MFSAF TSS v4.0 at Week 24
Hide Description The MFSAF v4.0 comprises 7 domains representing the 7 most relevant symptoms of MF identified through existing participant- and clinician-based evidence: fatigue, night sweats, pruritus, abdominal discomfort, pain under the left ribs, early satiety, and bone pain. Participants scored each symptom domain using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable). Data has been reported for Disease-related Fatigue domain measured using an 11-point numeric rating scale ranging from 0 (absent) to 10 (worst imaginable), higher score indicates worst outcome. An increase in score from Baseline indicated a worsening of fatigue and a decrease in score from Baseline indicated an improvement in fatigue. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Only those participants with data available at specified time points were analyzed.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 92 37
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-1.53  (0.20) -0.82  (0.31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0513
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.71
Confidence Interval (2-Sided) 95%
-1.42 to 0.00
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Change From Baseline in Cancer-related Fatigue as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at Week 24
Hide Description The EORTC QLQ-C30 is comprised of 5 functional scales (physical, role, emotional, social, cognitive), eight single item symptom scales (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea), as well as sub-scales assessing global health/quality of life and financial impact. Most items use a 4-point Likert scale from "not at all" to "very much" and a one-week recall period with the exception of the final two items which use a 7 point scale response from "very poor" to "excellent". Scores were averaged and transformed to a 0-100 scale, with higher scores representing better functioning/quality of life. An increase in scores from Baseline indicated an improved functioning/quality of life, and a decrease in scores from Baseline indicated a worsened functioning/quality of life. Baseline was the last assessment done before or on the day of first dose date. Change from Baseline was defined as the post-Baseline value minus Baseline value.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Only those participants with data available at specified time points were analyzed.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 89 35
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-14.34  (2.35) -3.52  (3.65)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0113
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -10.82
Confidence Interval (2-Sided) 95%
-19.15 to -2.48
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Change From Baseline in Physical Function Score as Assessed by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function Short Form 10b at Week 24
Hide Description PROMIS Physical Function Short Form 10b consists of 14 questions; each with a 5-point response. PROMIS short form assesses self-reported capability of a participant rather than actual performance of physical activities. This includes functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back) as well as instrumental activities of daily living, such as running errands. Participants scored each response on a scale from 1 (unable to do) to 5 (without any difficulty, or not at all). Total possible range of scores was 14 to 70, with higher scores corresponding to a greater physical function ability. An increase in score from Baseline indicated an improvement in physical function ability and a decrease in score from Baseline indicated a reduction in physical function ability. Baseline was last assessment done before or on the day of first dose date. Change from Baseline was defined as post-Baseline value minus Baseline value.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Analysis Set. Only those participants with data available at specified time points were analyzed.
Arm/Group Title MMB 200 mg QD + Placebo DAN 300 mg BID + Placebo
Hide Arm/Group Description:
Participants were randomized to receive 200 milligrams (mg) of MMB orally QD and a DAN-placebo orally twice daily (BID) during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who discontinued treatment prior to Week 24 due to splenic progression or other reasons, but completed assessments, were unblinded. Participants who discontinued MMB during the randomized treatment period were not eligible to receive MMB in the open-label extended treatment period. Participants who were randomized to MMB during the randomized treatment period with confirmed splenic progression could not proceed to the open-label extended treatment period.
Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
Overall Number of Participants Analyzed 89 32
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
1.19  (0.77) -0.11  (1.21)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MMB 200 mg QD + Placebo, DAN 300 mg BID + Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3570
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
-1.49 to 4.11
Estimation Comments [Not Specified]
Time Frame All-cause mortality, Serious adverse events (SAEs) and non-SAEs were collected up to Week 24 for Randomized Double-Blind Treatment Period and From Week 24 to a maximum of 151 weeks for the Open-Label Extended Treatment Period
Adverse Event Reporting Description Serious adverse events (SAEs) and non-SAEs were measured in the Safety analysis set, which included all participants in the ITT analysis set who received at least one dose of study drug. All-cause mortality was measured in the ITT analysis set, which included all randomized participants. Data are presented per treatment received.
 
Arm/Group Title MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period MMB 200 mg QD- Open-Label Extended Treatment Period DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period
Hide Arm/Group Description Participants were randomized to receive 200 mg of MMB orally QD and a DAN-placebo orally BID during the randomized 24-week double-blind treatment period. Participants were randomized to receive 300 mg of DAN orally BID and MMB-placebo orally QD during the randomized 24-week double-blind treatment period. Participants who completed the randomized treatment period or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants continued to receive 200 mg of MMB orally QD during the open-label extended treatment period. Participants who completed the randomized treatment period, discontinued treatment early due to splenic progression, or discontinued treatment early for other reasons but completed scheduled assessments through Week 24 were enrolled in an open-label extended treatment period. Participants who received DAN 300 mg BID during randomized period switched to receive 200 mg of MMB orally QD during open-label extended treatment period.
All-Cause Mortality
MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period MMB 200 mg QD- Open-Label Extended Treatment Period DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/130 (19.23%)      16/65 (24.62%)      23/93 (24.73%)      8/41 (19.51%)    
Hide Serious Adverse Events
MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period MMB 200 mg QD- Open-Label Extended Treatment Period DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/130 (34.62%)      26/65 (40.00%)      30/93 (32.26%)      12/41 (29.27%)    
Blood and lymphatic system disorders         
Anaemia  1  5/130 (3.85%)  5 3/65 (4.62%)  3 1/93 (1.08%)  1 1/41 (2.44%)  2
Blood loss anaemia  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Febrile neutropenia  1  1/130 (0.77%)  1 0/65 (0.00%)  0 2/93 (2.15%)  2 0/41 (0.00%)  0
Splenic haematoma  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Splenic infarction  1  1/130 (0.77%)  1 2/65 (3.08%)  2 1/93 (1.08%)  1 0/41 (0.00%)  0
Splenic vein thrombosis  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Thrombocytopenia  1  3/130 (2.31%)  4 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Cardiac disorders         
Acute myocardial infarction  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Atrial fibrillation  1  2/130 (1.54%)  2 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Cardiogenic shock  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Coronary artery disease  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Coronary artery stenosis  1  0/130 (0.00%)  0 1/65 (1.54%)  1 1/93 (1.08%)  1 0/41 (0.00%)  0
Myocardial ischaemia  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Arrhythmia  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Atrial thrombosis  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Cardiac arrest  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Cardiac failure  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Cardiac failure chronic  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Cardiac failure congestive  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Myocardial infarction  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Tachycardia  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Endocrine disorders         
Inappropriate antidiuretic hormone secretion  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Gastrointestinal disorders         
Gastric ulcer perforation  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Haematochezia  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Haemoperitoneum  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Melaena  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Oesophageal varices haemorrhage  1  1/130 (0.77%)  1 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Small intestinal obstruction  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/130 (0.77%)  1 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Enteritis  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Haemorrhagic erosive gastritis  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
General disorders         
Chest pain  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Death  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Disease progression  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
General physical health deterioration  1  2/130 (1.54%)  2 2/65 (3.08%)  2 1/93 (1.08%)  1 0/41 (0.00%)  0
Oedema peripheral  1  1/130 (0.77%)  1 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Pyrexia  1  3/130 (2.31%)  3 0/65 (0.00%)  0 1/93 (1.08%)  1 1/41 (2.44%)  1
Sudden death  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Complication associated with device  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  2
Multiple organ dysfunction syndrome  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Hepatobiliary disorders         
Cholangitis acute  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Cholecystitis acute  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Hepatitis  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Hepatotoxicity  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Immune system disorders         
Hypersensitivity  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Infections and infestations         
Biliary sepsis  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Bronchitis  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
COVID-19  1  3/130 (2.31%)  3 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
COVID-19 pneumonia  1  3/130 (2.31%)  3 0/65 (0.00%)  0 4/93 (4.30%)  4 0/41 (0.00%)  0
Cellulitis  1  2/130 (1.54%)  2 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Clostridium difficile colitis  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Cystitis  1  1/130 (0.77%)  1 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Enterococcal sepsis  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Escherichia sepsis  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Joint abscess  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Listeria sepsis  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Pneumonia  1  3/130 (2.31%)  4 6/65 (9.23%)  6 1/93 (1.08%)  1 1/41 (2.44%)  1
Pyelonephritis acute  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Septic shock  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Staphylococcal sepsis  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Streptococcal bacteraemia  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Tooth abscess  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Urinary tract infection  1  2/130 (1.54%)  2 0/65 (0.00%)  0 2/93 (2.15%)  2 1/41 (2.44%)  1
Abscess limb  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Endocarditis  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Enterobacter sepsis  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Escherichia infection  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Gastroenteritis rotavirus  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Infective exacerbation of chronic obstructive airways disease  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Periorbital cellulitis  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Pneumonia bacterial  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Pneumonia influenzal  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Pneumonia staphylococcal  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Pulmonary sepsis  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Splenic abscess  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Urosepsis  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Injury, poisoning and procedural complications         
Cervical vertebral fracture  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Fall  1  0/130 (0.00%)  0 1/65 (1.54%)  1 1/93 (1.08%)  1 0/41 (0.00%)  0
Femur fracture  1  0/130 (0.00%)  0 1/65 (1.54%)  1 1/93 (1.08%)  1 0/41 (0.00%)  0
Subdural haematoma  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 1/41 (2.44%)  1
Lower limb fracture  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Periprosthetic fracture  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Investigations         
Gamma-glutamyltransferase increased  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
General physical condition abnormal  1  1/130 (0.77%)  2 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Liver function test increased  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Metabolism and nutrition disorders         
Fluid overload  1  2/130 (1.54%)  2 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Hyperkalaemia  1  1/130 (0.77%)  1 1/65 (1.54%)  1 0/93 (0.00%)  0 1/41 (2.44%)  1
Hypoglycaemia  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Decreased appetite  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Musculoskeletal and connective tissue disorders         
Tenosynovitis  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Sarcopenia  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Acute myeloid leukaemia  1  1/130 (0.77%)  1 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Leukaemia cutis  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Metastatic malignant melanoma  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Tongue neoplasm malignant stage unspecified  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Transformation to acute myeloid leukaemia  1  3/130 (2.31%)  3 2/65 (3.08%)  2 0/93 (0.00%)  0 1/41 (2.44%)  1
Adenocarcinoma  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Basal cell carcinoma  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 1/41 (2.44%)  1
Squamous cell carcinoma of skin  1  0/130 (0.00%)  0 0/65 (0.00%)  0 2/93 (2.15%)  2 0/41 (0.00%)  0
Nervous system disorders         
Cerebrovascular accident  1  1/130 (0.77%)  1 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Subarachnoid haemorrhage  1  0/130 (0.00%)  0 1/65 (1.54%)  1 0/93 (0.00%)  0 0/41 (0.00%)  0
Syncope  1  3/130 (2.31%)  3 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Cerebral haemorrhage  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Psychiatric disorders         
Delirium  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Depression  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Personality change  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Renal and urinary disorders         
Acute kidney injury  1  4/130 (3.08%)  6 3/65 (4.62%)  3 2/93 (2.15%)  2 2/41 (4.88%)  2
Chronic kidney disease  1  0/130 (0.00%)  0 1/65 (1.54%)  1 1/93 (1.08%)  1 0/41 (0.00%)  0
Renal failure  1  2/130 (1.54%)  2 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Reproductive system and breast disorders         
Prostatitis  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Chronic obstructive pulmonary disease  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Dyspnoea  1  1/130 (0.77%)  1 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Pneumonia aspiration  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Pulmonary embolism  1  1/130 (0.77%)  1 1/65 (1.54%)  1 1/93 (1.08%)  1 0/41 (0.00%)  0
Acute respiratory failure  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
Pulmonary arterial hypertension  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Pulmonary oedema  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 1/41 (2.44%)  1
Restrictive pulmonary disease  1  0/130 (0.00%)  0 0/65 (0.00%)  0 1/93 (1.08%)  1 0/41 (0.00%)  0
Vascular disorders         
Aortic stenosis  1  0/130 (0.00%)  0 1/65 (1.54%)  2 0/93 (0.00%)  0 0/41 (0.00%)  0
Circulatory collapse  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Hypotension  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Shock haemorrhagic  1  1/130 (0.77%)  1 0/65 (0.00%)  0 0/93 (0.00%)  0 0/41 (0.00%)  0
Haematoma  1  0/130 (0.00%)  0 0/65 (0.00%)  0 0/93 (0.00%)  0 1/41 (2.44%)  1
1
Term from vocabulary, MedDRA v24.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
MMB 200 mg QD + Placebo- Randomized Double-Blind Treatment Period DAN 300 mg BID + Placebo- Randomized Double-Blind Treatment Period MMB 200 mg QD- Open-Label Extended Treatment Period DAN 300 mg BID to MMB 200 mg QD- Open-Label Extended Treatment Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   108/130 (83.08%)      55/65 (84.62%)      57/93 (61.29%)      28/41 (68.29%)    
Blood and lymphatic system disorders         
Anaemia  1  12/130 (9.23%)  34 6/65 (9.23%)  11 9/93 (9.68%)  18 3/41 (7.32%)  6
Neutropenia  1  7/130 (5.38%)  11 2/65 (3.08%)  5 5/93 (5.38%)  9 2/41 (4.88%)  2
Thrombocytopenia  1  28/130 (21.54%)  50 7/65 (10.77%)  11 13/93 (13.98%)  22 7/41 (17.07%)  10
Gastrointestinal disorders         
Abdominal pain  1  10/130 (7.69%)  12 6/65 (9.23%)  6 3/93 (3.23%)  3 1/41 (2.44%)  2
Abdominal pain upper  1  3/130 (2.31%)  3 5/65 (7.69%)  6 2/93 (2.15%)  3 1/41 (2.44%)  1
Constipation  1  11/130 (8.46%)  13 5/65 (7.69%)  5 4/93 (4.30%)  4 2/41 (4.88%)  2
Diarrhoea  1  29/130 (22.31%)  40 6/65 (9.23%)  7 16/93 (17.20%)  21 5/41 (12.20%)  7
Nausea  1  21/130 (16.15%)  28 6/65 (9.23%)  6 8/93 (8.60%)  10 0/41 (0.00%)  0
Vomiting  1  9/130 (6.92%)  10 0/65 (0.00%)  0 3/93 (3.23%)  3 1/41 (2.44%)  1
General disorders         
Asthenia  1  17/130 (13.08%)  20 6/65 (9.23%)  8 12/93 (12.90%)  15 0/41 (0.00%)  0
Fatigue  1  8/130 (6.15%)  10 6/65 (9.23%)  10 6/93 (6.45%)  11 3/41 (7.32%)  3
Oedema peripheral  1  9/130 (6.92%)  9 9/65 (13.85%)  10 3/93 (3.23%)  3 1/41 (2.44%)  1
Pyrexia  1  11/130 (8.46%)  13 5/65 (7.69%)  6 12/93 (12.90%)  13 3/41 (7.32%)  4
Infections and infestations         
COVID-19  1  9/130 (6.92%)  9 0/65 (0.00%)  0 8/93 (8.60%)  8 0/41 (0.00%)  0
Injury, poisoning and procedural complications         
Fall  1  7/130 (5.38%)  9 3/65 (4.62%)  3 4/93 (4.30%)  6 0/41 (0.00%)  0
Investigations         
Alanine aminotransferase increased  1  9/130 (6.92%)  13 5/65 (7.69%)  11 2/93 (2.15%)  4 1/41 (2.44%)  1
Aspartate aminotransferase increased  1  7/130 (5.38%)  9 4/65 (6.15%)  5 3/93 (3.23%)  3 1/41 (2.44%)  1
Blood alkaline phosphatase increased  1  10/130 (7.69%)  18 0/65 (0.00%)  0 3/93 (3.23%)  3 1/41 (2.44%)  1
Blood creatinine increased  1  10/130 (7.69%)  18 10/65 (15.38%)  16 7/93 (7.53%)  13 4/41 (9.76%)  4
Platelet count decreased  1  9/130 (6.92%)  24 3/65 (4.62%)  4 3/93 (3.23%)  7 1/41 (2.44%)  2
Weight decreased  1  14/130 (10.77%)  16 3/65 (4.62%)  4 9/93 (9.68%)  9 7/41 (17.07%)  7
Metabolism and nutrition disorders         
Decreased appetite  1  9/130 (6.92%)  13 6/65 (9.23%)  8 4/93 (4.30%)  5 1/41 (2.44%)  1
Hyperkalaemia  1  6/130 (4.62%)  7 6/65 (9.23%)  12 2/93 (2.15%)  3 2/41 (4.88%)  2
Hyperuricaemia  1  9/130 (6.92%)  9 4/65 (6.15%)  6 3/93 (3.23%)  3 3/41 (7.32%)  3
Hyponatraemia  1  3/130 (2.31%)  5 4/65 (6.15%)  4 3/93 (3.23%)  3 0/41 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  4/130 (3.08%)  5 2/65 (3.08%)  3 1/93 (1.08%)  1 3/41 (7.32%)  4
Nervous system disorders         
Dizziness  1  8/130 (6.15%)  9 1/65 (1.54%)  1 1/93 (1.08%)  1 4/41 (9.76%)  4
Paraesthesia  1  8/130 (6.15%)  10 1/65 (1.54%)  1 1/93 (1.08%)  1 0/41 (0.00%)  0
Renal and urinary disorders         
Acute kidney injury  1  2/130 (1.54%)  2 5/65 (7.69%)  5 1/93 (1.08%)  1 1/41 (2.44%)  1
Respiratory, thoracic and mediastinal disorders         
Cough  1  9/130 (6.92%)  10 2/65 (3.08%)  2 8/93 (8.60%)  9 2/41 (4.88%)  2
Dyspnoea  1  9/130 (6.92%)  10 10/65 (15.38%)  12 7/93 (7.53%)  8 0/41 (0.00%)  0
Epistaxis  1  7/130 (5.38%)  7 4/65 (6.15%)  6 1/93 (1.08%)  2 3/41 (7.32%)  3
Skin and subcutaneous tissue disorders         
Pruritus  1  13/130 (10.00%)  14 7/65 (10.77%)  7 6/93 (6.45%)  7 1/41 (2.44%)  1
Rash  1  3/130 (2.31%)  3 4/65 (6.15%)  4 0/93 (0.00%)  0 0/41 (0.00%)  0
Night sweats  1  4/130 (3.08%)  4 4/65 (6.15%)  5 2/93 (2.15%)  2 0/41 (0.00%)  0
Vascular disorders         
Hypertension  1  6/130 (4.62%)  6 6/65 (9.23%)  6 3/93 (3.23%)  3 5/41 (12.20%)  5
1
Term from vocabulary, MedDRA v24.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GlaxoSmithKline (GSK) agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: Sierra Oncology LLC - a GSK company
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
Layout table for additonal information
Responsible Party: Sierra Oncology LLC - a GSK company
ClinicalTrials.gov Identifier: NCT04173494    
Other Study ID Numbers: SRA-MMB-301
First Submitted: November 20, 2019
First Posted: November 22, 2019
Results First Submitted: December 1, 2022
Results First Posted: December 22, 2022
Last Update Posted: November 1, 2023