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

• 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: Sierra Oncology LLC - a GSK company
• 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

Participant Flow

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
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.

Baseline Characteristics

Arm/Group Title		MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo	Total
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
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%

Outcome Measures

1. Primary Outcome

Title	Total Symptom Score (TSS) Response Rate at Week 24
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo
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)

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
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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo
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)

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
Description	Percentage of participants with zero RBC units transfused over 24-weeks were reported.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo
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)

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
Description	Percentage of participants with <=4 RBC units transfused over 24-weeks were reported.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo
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)

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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set.

Arm/Group Title	MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo
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)

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
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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo
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)

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
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

Outcome Measure Data

Analysis Population Description

ITT Analysis Set

Arm/Group Title	MMB 200 mg QD + Placebo	DAN 300 mg BID + Placebo
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)

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

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

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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

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
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

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)
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

Outcome Measure Data

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
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.

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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]

Adverse Events

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
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: GSK Response Center
• Organization: Sierra Oncology LLC - a GSK company
• Phone: 866-435-7343
• EMail: GSKClinicalSupportHD@gsk.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gerds A, Verstovsek S, Vannucchi A, Al-Ali HK, Lavie D, Kuykendall A, Grosicki S, Iurlo A, Goh YT, Lazaroiu M, Egyed M, Fox ML, McLornan D, Perkins A, Yoon SS, Gupta V, Kiladjian JJ, Donahue R, Kawashima J, Mesa R. MPN-483 Thrombocytopenic Myelofibrosis (MF) Patients Previously Treated With a JAK Inhibitor in a Phase 3 Randomized Study of Momelotinib (MMB) versus Danazol (DAN) [MOMENTUM]. Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S340. doi: 10.1016/S2152-2650(22)01464-1.

• 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