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A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MEDALIST)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02631070
Recruitment Status : Completed
First Posted : December 15, 2015
Results First Posted : May 22, 2020
Last Update Posted : December 17, 2021
Sponsor:
Collaborator:
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Myelodysplastic Syndromes
Interventions Drug: Luspatercept
Other: Placebo
Enrollment 229
Recruitment Details  
Pre-assignment Details 229 participants were randomized and treated.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Period Title: Overall Study
Started 153 76
Completed 4 12
Not Completed 149 64
Reason Not Completed
Withdrawal by Subject             35             13
Death             45             24
Lost to Follow-up             5             1
Transition to rollover protocol             52             21
Other reasons             12             5
Arm/Group Title Luspatercept Placebo Total
Hide Arm/Group Description Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle Total of all reporting groups
Overall Number of Baseline Participants 153 76 229
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 153 participants 76 participants 229 participants
70.5  (8.68) 70.7  (10.88) 70.6  (9.44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 76 participants 229 participants
Female
59
  38.6%
26
  34.2%
85
  37.1%
Male
94
  61.4%
50
  65.8%
144
  62.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 76 participants 229 participants
Hispanic or Latino
3
   2.0%
4
   5.3%
7
   3.1%
Not Hispanic or Latino
115
  75.2%
52
  68.4%
167
  72.9%
Unknown or Not Reported
35
  22.9%
20
  26.3%
55
  24.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 153 participants 76 participants 229 participants
Black or African American
1
   0.7%
0
   0.0%
1
   0.4%
White
107
  69.9%
51
  67.1%
158
  69.0%
Not Collected or Reported
44
  28.8%
24
  31.6%
68
  29.7%
Other
1
   0.7%
1
   1.3%
2
   0.9%
1.Primary Outcome
Title Percentage Of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 to Week 24
Hide Description RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during the first 24 weeks of study treatment. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 24 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to or on the cut-off date were counted as non-responders.
Time Frame From Week 1 through Week 24 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
37.91
(30.20 to 46.10)
13.16
(6.49 to 22.87)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
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 Common Risk Difference on Response Rate
Estimated Value 24.56
Confidence Interval (2-Sided) 95%
14.48 to 34.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
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 Odds Ratio (OR)
Estimated Value 5.065
Confidence Interval (2-Sided) 95%
2.278 to 11.259
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 24
Hide Description RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 24 weeks of treatment.
Time Frame From Week 1 through Week 24 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
28.10
(21.14 to 35.93)
7.89
(2.95 to 16.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Common Risk Difference on Response Rate
Estimated Value 20.00
Confidence Interval (2-Sided) 95%
10.92 to 29.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 5.071
Confidence Interval (2-Sided) 95%
2.002 to 12.844
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks From Week 1 to Week 48
Hide Description RBC-TI Response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 84-day (12-week) period (ie, Days 1 to 84, Days 2 to 85, Days 3 to 86, etc.) during the first 48 weeks of treatment.
Time Frame From Week 1 through Week 48 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
33.33
(25.93 to 41.40)
11.84
(5.56 to 21.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Common Risk Difference on Response Rate
Estimated Value 21.37
Confidence Interval (2-Sided) 95%
11.23 to 31.51
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.045
Confidence Interval (2-Sided) 95%
1.827 to 8.956
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence (RBC-TI) ≥ 8 Weeks From Week 1 Through Week 48
Hide Description RBC-TI response was defined as the absence of any Red Blood Cells (RBC) transfusion during any consecutive 56-day (8-week) period (ie, Days 1 to 56, Days 2 to 57, Days 3 to 58, etc.) during Week 1 through Week 48. Participants had to have at least 56 days (≥ 8 weeks) of transfusion independence prior to (and including) the Week 48 cut-off date to qualify as a responder. Participants who failed to achieve RBC-TI at least 56 days prior to Week 48 were counted as non-responders.
Time Frame From Week 1 through Week 48 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
45.10
(37.05 to 53.34)
15.79
(8.43 to 25.96)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
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 Common Risk Difference on Response Rate
Estimated Value 29.55
Confidence Interval (2-Sided) 95%
18.73 to 40.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
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 Odds Ratio (OR)
Estimated Value 5.306
Confidence Interval (2-Sided) 95%
2.526 to 11.146
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in RBC Units Transfused Over Fixed 16-Week Period
Hide Description Mean change in total number of Red Blood Cells (RBC) units transfused over a fixed 16-week period (Week 9-24 or Week 33-48) from the total number of RBC units transfused in the 16 weeks immediately on or prior to first dose of study treatment.
Time Frame At Baseline (16 weeks prior to first dose of study treatment) and Weeks 9 to 24 or Weeks 33 to 48
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with available measurements at the indicated timepoints
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 128 68
Mean (Standard Deviation)
Unit of Measure: Units
Weeks 9 to 24 Number Analyzed 128 participants 68 participants
-3.0  (5.17) 0.4  (4.25)
Weeks 33 to 48 Number Analyzed 78 participants 12 participants
-4.9  (4.22) -3.9  (7.14)
6.Secondary Outcome
Title Percentage of Participants Who Achieved a Modified Hematologic Erythroid Response (mHI-E) Over Any Consecutive 56-Day Period
Hide Description A modified HI-E response was defined as the percentage of participants meeting the modified HI-E per the International Working Group (IWG) sustained over 56-day consecutive period during the Treatment period. For participants with a baseline RBC transfusion burden of ≥ 4 units/8 weeks, a mHI-E was defined as a reduction in RBC transfusion of at least 4 units/8 weeks; for participants with baseline RBC transfusion burden of <4 units/8 weeks, mHI-E, was defined as a mean increase in hemoglobin of ≥ 1.5 g/dL for 8 weeks in the absence of RBC transfusions.
Time Frame Week 1 through 24 or Week 1 Through Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Week 1 Through Week 24
52.9
(44.72 to 61.05)
11.8
(5.56 to 21.29)
Week 1 Through Week 48
58.8
(50.59 to 66.71)
17.1
(9.43 to 27.47)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 1 -24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 1 - 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants Who Achieved a Mean Hemoglobin (Hgb) Increase of at Least 1.0 g/dL Over Any Consecutive 56-Day Period in Absence of Red Blood Cells (RBC) Transfusions
Hide Description A mean hgb increase of ≥ 1.0 g/dL was analyzed as the percentage of participants with a hgb increase ≥ 1.0 g/dL compared with baseline (after applying the 14/3 day rule) that was sustained over any consecutive 56-day (8-week) period in the absence of RBC transfusions during the treatment period. (Week 1 through Week 24 and Week 1 through Week 48).
Time Frame Week 1 though Week 24 and Week 1 through 48
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Week 1 Through Week 24
35.3
(27.75 to 43.42)
7.9
(2.95 to 16.40)
Week 1 Through Week 48
41.2
(33.29 to 49.41)
10.5
(4.66 to 19.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 1 Through Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 1 Through Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
8.Secondary Outcome
Title Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24
Hide Description Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 24. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method.
Time Frame From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants who achieved RBC-TI ≥ 8 weeks during Week 1 through Week 24 of study treatment
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 58 10
Median (95% Confidence Interval)
Unit of Measure: Weeks
30.6
(20.6 to 40.6)
13.6
(9.1 to 54.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0445
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.446
Confidence Interval (2-Sided) 95%
0.196 to 1.013
Estimation Comments HR is from the Cox proportional hazards model
9.Secondary Outcome
Title Duration of Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48
Hide Description Duration of RBC-TI was defined as the longest duration of response for participants who achieved RBC-TI of ≥ 8 weeks during the treatment period Week 1 through Week 48. Participants who maintained RBC-TI through the end of the treatment period were censored at the date of IP discontinuation or death, whichever occurred first. Median was estimated from unstratified Kaplan Meier method.
Time Frame From start of study treatment to 16 weeks after last dose, up to approximately 93 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants who achieved RBC-TI ≥ 8 weeks during Week 1 through Week 48 of study treatment
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 69 12
Median (95% Confidence Interval)
Unit of Measure: Weeks
30.6
(20.6 to 50.9)
18.6 [1] 
(10.9 to NA)
[1]
Upper limit could not be estimated due to insufficient number of events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5121
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.784
Confidence Interval (2-Sided) 95%
0.362 to 1.699
Estimation Comments HR is from the Cox proportional hazards model
10.Secondary Outcome
Title Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Quality of Life Score
Hide Description

The EORTC questionnaire is a validated health-related quality of life (HRQoL) measure applicable to participants with any cancer diagnosis. Version 3.0 of the questionnaire was used in the study.

It is composed of 30 items that address 15 domains, including one global health status, functional domains, and symptom domains. Domain scores are transformed to a 0 to 100 scale, where higher scores on the global quality of life score indicate better function. As such, a positive change from Baseline score indicates an improvement in quality of life.
Time Frame Baseline and Cycle 3, Day 1 (C3 D1), C5 D1, C7 D1, Week 25, every other cycle during extension phase (C1 D1, C3 D1, C5 D1, etc. up to C59 D1) and end of treatment. Each cycle is composed of 21 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants who completed the EORTC QLQ-C30 assessment at baseline and at least one post-baseline assessment visit.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 149 76
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Cycle 3 Day 1 (C3 D1) Number Analyzed 133 participants 69 participants
-4.1  (21.01) 0.1  (15.95)
C5 D1 Number Analyzed 129 participants 65 participants
-2.4  (20.73) 2.2  (17.13)
C7 D1 Number Analyzed 108 participants 59 participants
-2.1  (23.04) -0.6  (18.63)
Week 25 Number Analyzed 110 participants 53 participants
-1.8  (21.75) 0.2  (18.88)
Extension Phase C1 D1 Number Analyzed 48 participants 8 participants
0.0  (25.32) 6.3  (14.60)
Extension Phase C3 D1 Number Analyzed 83 participants 17 participants
2.0  (19.68) -3.9  (26.86)
Extension Phase C5 D1 Number Analyzed 77 participants 15 participants
0.8  (18.40) 0.6  (20.04)
Extension Phase C7 D1 Number Analyzed 74 participants 13 participants
-0.5  (20.03) 3.8  (20.87)
Extension Phase C9 D1 Number Analyzed 69 participants 7 participants
-2.4  (18.42) 11.9  (19.75)
Extension Phase C11 D1 Number Analyzed 60 participants 7 participants
-1.8  (19.53) 4.8  (24.47)
Extension Phase C13 D1 Number Analyzed 58 participants 6 participants
-2.6  (20.84) 8.3  (24.15)
Extension Phase C15 D1 Number Analyzed 57 participants 6 participants
3.1  (18.27) 4.2  (27.26)
Extension Phase C17 D1 Number Analyzed 55 participants 3 participants
-0.6  (19.03) 13.9  (26.79)
Extension Phase C19 D1 Number Analyzed 51 participants 3 participants
-1.6  (18.78) -16.7  (14.43)
Extension Phase C21 D1 Number Analyzed 45 participants 2 participants
3.1  (18.32) 4.2  (17.68)
Extension Phase C23 D1 Number Analyzed 38 participants 1 participants
0.9  (17.84) 16.7 [1]   (NA)
Extension Phase C25 D1 Number Analyzed 37 participants 1 participants
-2.0  (18.15) 16.7 [1]   (NA)
Extension Phase C27 D1 Number Analyzed 37 participants 0 participants
2.5  (20.40)
Extension Phase C29 D1 Number Analyzed 36 participants 0 participants
2.1  (21.12)
Extension Phase C31 D1 Number Analyzed 33 participants 0 participants
-0.3  (15.93)
Extension Phase C33 D1 Number Analyzed 34 participants 0 participants
-1.5  (19.41)
Extension Phase C35 D1 Number Analyzed 30 participants 0 participants
3.6  (23.33)
Extension Phase C37 D1 Number Analyzed 31 participants 0 participants
0.5  (22.04)
Extension Phase C39 D1 Number Analyzed 26 participants 0 participants
0.3  (23.63)
Extension Phase C41 D1 Number Analyzed 24 participants 0 participants
6.6  (20.11)
Extension Phase C43 D1 Number Analyzed 19 participants 0 participants
4.8  (15.29)
Extension Phase C45 D1 Number Analyzed 15 participants 0 participants
-2.2  (21.24)
Extension Phase C47 D1 Number Analyzed 12 participants 0 participants
1.4  (19.08)
Extension Phase C49 D1 Number Analyzed 11 participants 0 participants
-3.8  (16.40)
Extension Phase C51 D1 Number Analyzed 3 participants 0 participants
8.3  (8.33)
Extension Phase C53 D1 Number Analyzed 4 participants 0 participants
12.5  (10.76)
Extension Phase C55 D1 Number Analyzed 3 participants 0 participants
2.8  (17.35)
Extension Phase C57 D1 Number Analyzed 2 participants 0 participants
12.5  (5.89)
Extension Phase C59 D1 Number Analyzed 1 participants 0 participants
16.7 [1]   (NA)
End of Treatment Number Analyzed 88 participants 33 participants
-9.2  (23.97) -0.8  (23.07)
[1]
No standard deviation could be determined because a single participant was analyzed
11.Secondary Outcome
Title Percentage of Participants Who Achieved a Hematologic Improvement in Neutrophil Response (HI-N) Over Any Consecutive 56-day Period
Hide Description Percentage of participants who achieved a hematologic improvement in neutrophil response (HI-N) per IWG criteria sustained over any consecutive 56-day (8-week) period, during the treatment period (Week 1 to Week 24 and Week 1 to Week 48) HI-N was defined as at least a 100% increase and an absolute increase > 0.5 X 10^9/L.
Time Frame Week 1 through Week 24 or Week 1 Through Week 48 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with available measurements
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 15 10
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Week 1 Through Week 24
13.3
(1.66 to 40.46)
0
(0.00 to 30.85)
Week 1 Through Week 48
20.0
(4.33 to 48.09)
10.0
(0.25 to 44.50)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 1 -24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2382
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 1 - 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5127
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants Who Achieved a Hematologic Improvement in Platelet Response (HI-P) Over Any Consecutive 56-day Period
Hide Description

Percentage of participants who achieved a hematologic improvement platelet response (HI-P) was defined as the percentage of participants meeting the HI-P criteria per the IWG sustained over any consecutive 56-day (8-week) period (Week 1 to Week 24 and Week 1 to Week 48) during the treatment period. HI - P reponse was defined as:

  • Absolute increase of ≥ 30 X 10^9/L in platelets for participants starting with > 20 X 10^9/L platelets
  • Increase in platelets from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%
Time Frame Week 1 through Week 24 or Week 1 Through Week 48 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with available measurements
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 8 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Week 1 Through Week 24
50.0
(15.70 to 84.30)
33.3
(4.33 to 77.72)
Week 1 Through Week 48
62.5
(24.49 to 91.48)
33.3
(4.33 to 77.72)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 1 -24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5479
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 1 - 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2980
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Mean Serum Ferritin
Hide Description Mean change from baseline in mean serum ferritin was calculated as the difference of postbaseline mean serum ferritin (averaged over the specified timepoints) and baseline mean serum ferritin.
Time Frame Baseline and Week 9 through Week 24 and Week 33 through Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with available measurements
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 148 74
Least Squares Mean (Standard Error)
Unit of Measure: ug/L
Weeks 9-24 Number Analyzed 148 participants 74 participants
-2.7  (54.05) 226.5  (68.02)
Weeks 33-48 Number Analyzed 89 participants 16 participants
-72.0  (74.76) 247.4  (140.96)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 9 Through 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0024
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -229.1
Confidence Interval (2-Sided) 95%
-375.8 to -82.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 74.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Week 33 Through 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0294
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -319.5
Confidence Interval (2-Sided) 95%
-606.3 to -32.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 144.57
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Mean Daily Dose of Iron Chelation Therapy (ICT)
Hide Description Mean change from baseline in mean daily dose of ICT averaged over Week 9 to Week 24 or Week 33 to Week 48. For each participant, the mean change in daily dose of ICT was calculated as the difference of postbaseline mean daily dose and baseline mean daily dose.
Time Frame Baseline and Week 9 through Week 24 and Week 33 through Week 48 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants with available measurements
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 128 68
Least Squares Mean (Standard Error)
Unit of Measure: mg/day
Weeks 9-24 Number Analyzed 128 participants 68 participants
10.0  (29.25) 51.0  (35.92)
Weeks 33-48 Number Analyzed 78 participants 12 participants
-148.8  (46.13) -123.8  (92.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Weeks 9 Through 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3087
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -41.0
Confidence Interval (2-Sided) 95%
-120.3 to 38.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 40.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments Weeks 33 Through 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7903
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -24.9
Confidence Interval (2-Sided) 95%
-210.7 to 160.8
Parameter Dispersion
Type: Standard Error of the Mean
Value: 93.42
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 24
Hide Description Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 24
Time Frame From first dose to Week 24 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who achieved RBC-TI ≥ 8 weeks during Week 1 through Week 24
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 58 10
Mean (Standard Deviation)
Unit of Measure: Days
17.2  (29.40) 26.0  (31.83)
16.Secondary Outcome
Title Time to Red Blood Cell Transfusion Independence (RBC-TI) - Week 1 Through Week 48
Hide Description Time to RBC-TI was defined as the time between first dose date and the date of onset of RBC-TI first observed for participants who achieved RBC-TI of ≥ 8 weeks during Week 1 through Week 48
Time Frame From first dose to Week 48 of study treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who achieved RBC-TI ≥ 8 weeks during Week 1 through Week 48
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 69 12
Mean (Standard Deviation)
Unit of Measure: Days
40.3  (61.03) 57.2  (79.18)
17.Secondary Outcome
Title Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)
Hide Description Percentage of participants progressing to AML throughout the course of the study
Time Frame From randomization to study completion (up to approximately 57 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Number
Unit of Measure: Percentage of Participants
2.6 3.9
18.Secondary Outcome
Title Time to Acute Myeloid Leukemia (AML) Progression
Hide Description Time to AML progression was defined as the time between randomization date and the first diagnosis of AML as per World Health Organization (WHO) classification of ≥ 20% blasts in peripheral blood or bone marrow. Participants with a diagnosis of AML were considered to have had an event, participants who did not progress to AML at the time of analysis were censored at the last assessment date which did not indicate progression to AML.
Time Frame From randomization to study completion (up to approximately 57 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants who progressed to AML
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 4 3
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median was not estimable due to the insufficient number of events
19.Secondary Outcome
Title Overall Survival
Hide Description Overall Survival was defined as the time from the date of study drug randomization to death due to any cause. Overall survival was censored at the last date that the participant was known to be alive for participants who were alive at the time of analysis and for those who discontinued from the study or were lost to follow-up.
Time Frame From randomization to study completion (up to approximately 57 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Median (95% Confidence Interval)
Unit of Measure: Months
46.0 [1] 
(42.0 to NA)
NA [2] 
(43.1 to NA)
[1]
Upper limit could not be estimated because of the insufficient number of events
[2]
Median and Upper limit could not be estimated because of the insufficient number of events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Luspatercept, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9580
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.986
Confidence Interval (2-Sided) 95%
0.595 to 1.636
Estimation Comments HR is from the Cox proportional hazards model
20.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide Description

The outcome measure describes the number of participants who experienced different types of Treatment-emergent adverse events (TEAEs).

TEAEs were defined as Adverse Events (AEs) that started on or after the day of the first dose and on or before 42 days after the last dose of IP.

The investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the event. The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death.
Time Frame From date of first dose up to 42 days after the last dose (up to approximately 83 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Count of Participants
Unit of Measure: Participants
≥ 1 TEAE
151
  98.7%
70
  92.1%
≥ 1 Suspected Related TEAE
71
  46.4%
26
  34.2%
≥ 1 Serious TEAE
66
  43.1%
23
  30.3%
≥ 1 Suspected Related Serious TEAE
6
   3.9%
0
   0.0%
≥ 1 TEAE CTCAE Toxicity Grade (GR) 5
8
   5.2%
4
   5.3%
≥ 1 Suspected Related TEAE With CTCAE GR 5
0
   0.0%
0
   0.0%
≥ 1 TEAE with CTCAE GR 3 or 4
86
  56.2%
34
  44.7%
≥ 1 Suspected Related TEAE With CTCAE GR 3 or 4
13
   8.5%
3
   3.9%
≥ 1 TEAE Leading to Dose Interruption
42
  27.5%
4
   5.3%
≥ 1 TEAE Leading to Dose Reduction
9
   5.9%
0
   0.0%
≥ 1 TEAE Leading to Study Drug Discontinuation
22
  14.4%
6
   7.9%
21.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F)
Hide Description Apparent total plasma clearance was calculated as Dose/Area Under the Curve to infinity (ꝏ).
Time Frame Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/day
0.516
(41.2%)
22.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F)
Hide Description Apparent volume of distribution of luspatercept was calculated according to the equation Vz = (CL)/λ.
Time Frame Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
9.68
(26.5%)
23.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2)
Hide Description Terminal phase half-life was calculated according to the following equation: t1/2 = 0.693/λz.
Time Frame Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population Included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Day
13.0
(31.6%)
24.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax)
Hide Description Tmax was defined as the observed time to maximum plasma concentration of luspatercept.
Time Frame Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population Included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 0
Median (Full Range)
Unit of Measure: Day
5.40
(3.12 to 6.69)
25.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the First Dose (Cmax)
Hide Description Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration versus time.
Time Frame Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population Included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
5.77
(20.5%)
26.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax) at Steady State
Hide Description Cmax was defined as the observed maximum plasma concentration, obtained directly from the observed concentration at a steady state.
Time Frame Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
9.17
(29.9%)
27.Secondary Outcome
Title Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Area Under the Curve at Steady State for Starting Dose (AUC^ss)
Hide Description Area under the curve steady state was defined as the area under the plasma concentration-time curve for a steady state. calculated by the linear trapezoidal rule.
Time Frame Blood serum samples taken pre-dose at Cycle 1 Day 1 (C1, D1), C1 D8, C1 D15, C2 D1, C4 D1, C5 D8, C6 D1 and Week 25 visit, extension phase C4 D1 and Day 1 of every fourth treatment cycle thereafter.
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population included all participants who received at least 1 dose of luspatercept and had measurable luspatercept serum concentrations.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day/μg/mL
145
(38.3%)
28.Secondary Outcome
Title Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA)
Hide Description Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as "treatment-emergent" if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as "preexisting" if the baseline sample was ADA positive and the participant was not qualified for "treatment-emergent."
Time Frame From randomization to 1 year post first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population of participants with ADA samples collected.
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description:
Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle
Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
Overall Number of Participants Analyzed 153 76
Measure Type: Count of Participants
Unit of Measure: Participants
Pre-Existing ADA
7
   4.6%
2
   2.6%
Treatment Emergent ADA
11
   7.2%
3
   3.9%
Treatment Emergent Neutralizing ADA
5
   3.3%
2
   2.6%
Time Frame All-cause mortality was assessed from first dose to study completion (up to approximately 57 months). SAEs and Other AEs were assessed from first dose to 100 days following last dose (up to approximately 91 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Luspatercept Placebo
Hide Arm/Group Description Luspatercept 1.0 mg/Kg SC on Day 1 of each 21-day treatment cycle Placebo (Volume equivalent to experimental arm) SC on Day 1 of each 21-day treatment cycle
All-Cause Mortality
Luspatercept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   45/153 (29.41%)   24/76 (31.58%) 
Hide Serious Adverse Events
Luspatercept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   66/153 (43.14%)   23/76 (30.26%) 
Blood and lymphatic system disorders     
Anaemia † 1  3/153 (1.96%)  0/76 (0.00%) 
Disseminated intravascular coagulation † 1  1/153 (0.65%)  0/76 (0.00%) 
Febrile neutropenia † 1  1/153 (0.65%)  0/76 (0.00%) 
Cardiac disorders     
Acute myocardial infarction † 1  1/153 (0.65%)  0/76 (0.00%) 
Angina pectoris † 1  3/153 (1.96%)  0/76 (0.00%) 
Aortic valve stenosis † 1  1/153 (0.65%)  0/76 (0.00%) 
Arteriosclerosis coronary artery † 1  1/153 (0.65%)  0/76 (0.00%) 
Atrial fibrillation † 1  2/153 (1.31%)  0/76 (0.00%) 
Atrioventricular block † 1  2/153 (1.31%)  0/76 (0.00%) 
Atrioventricular block second degree † 1  1/153 (0.65%)  0/76 (0.00%) 
Bradycardia † 1  1/153 (0.65%)  0/76 (0.00%) 
Cardiac failure † 1  2/153 (1.31%)  0/76 (0.00%) 
Cardiac failure acute † 1  1/153 (0.65%)  0/76 (0.00%) 
Coronary artery disease † 1  1/153 (0.65%)  0/76 (0.00%) 
Myocardial infarction † 1  0/153 (0.00%)  1/76 (1.32%) 
Supraventricular tachycardia † 1  1/153 (0.65%)  0/76 (0.00%) 
Gastrointestinal disorders     
Abdominal pain † 1  1/153 (0.65%)  0/76 (0.00%) 
Abdominal pain upper † 1  1/153 (0.65%)  0/76 (0.00%) 
Ascites † 1  1/153 (0.65%)  0/76 (0.00%) 
Constipation † 1  1/153 (0.65%)  0/76 (0.00%) 
Duodenal ulcer † 1  1/153 (0.65%)  0/76 (0.00%) 
Duodenal ulcer haemorrhage † 1  1/153 (0.65%)  0/76 (0.00%) 
Dysphagia † 1  1/153 (0.65%)  0/76 (0.00%) 
Gastrointestinal haemorrhage † 1  1/153 (0.65%)  0/76 (0.00%) 
Nausea † 1  1/153 (0.65%)  0/76 (0.00%) 
Pancreatitis acute † 1  1/153 (0.65%)  0/76 (0.00%) 
Vomiting † 1  1/153 (0.65%)  0/76 (0.00%) 
General disorders     
Asthenia † 1  1/153 (0.65%)  0/76 (0.00%) 
Chest pain † 1  1/153 (0.65%)  0/76 (0.00%) 
Death † 1  0/153 (0.00%)  1/76 (1.32%) 
Gait disturbance † 1  1/153 (0.65%)  0/76 (0.00%) 
General physical health deterioration † 1  0/153 (0.00%)  1/76 (1.32%) 
Generalised oedema † 1  1/153 (0.65%)  0/76 (0.00%) 
Multiple organ dysfunction syndrome † 1  1/153 (0.65%)  0/76 (0.00%) 
Non-cardiac chest pain † 1  1/153 (0.65%)  0/76 (0.00%) 
Pyrexia † 1  3/153 (1.96%)  2/76 (2.63%) 
Hepatobiliary disorders     
Cholangitis † 1  0/153 (0.00%)  1/76 (1.32%) 
Cholelithiasis † 1  1/153 (0.65%)  0/76 (0.00%) 
Hyperbilirubinaemia † 1  1/153 (0.65%)  0/76 (0.00%) 
Infections and infestations     
Abdominal infection † 1  1/153 (0.65%)  0/76 (0.00%) 
Bacteraemia † 1  0/153 (0.00%)  1/76 (1.32%) 
Bronchitis † 1  2/153 (1.31%)  0/76 (0.00%) 
Cellulitis † 1  1/153 (0.65%)  1/76 (1.32%) 
Diverticulitis † 1  0/153 (0.00%)  1/76 (1.32%) 
Endocarditis † 1  1/153 (0.65%)  0/76 (0.00%) 
Enterocolitis infectious † 1  0/153 (0.00%)  1/76 (1.32%) 
Epididymitis † 1  1/153 (0.65%)  0/76 (0.00%) 
Escherichia urinary tract infection † 1  1/153 (0.65%)  0/76 (0.00%) 
Gastroenteritis † 1  1/153 (0.65%)  0/76 (0.00%) 
Localised infection † 1  1/153 (0.65%)  0/76 (0.00%) 
Lower respiratory tract infection † 1  2/153 (1.31%)  0/76 (0.00%) 
Metapneumovirus infection † 1  0/153 (0.00%)  1/76 (1.32%) 
Orchitis † 1  1/153 (0.65%)  0/76 (0.00%) 
Parainfluenzae virus infection † 1  1/153 (0.65%)  0/76 (0.00%) 
Pharyngitis † 1  1/153 (0.65%)  0/76 (0.00%) 
Pneumonia † 1  8/153 (5.23%)  2/76 (2.63%) 
Pneumonia moraxella † 1  1/153 (0.65%)  0/76 (0.00%) 
Pneumonia staphylococcal † 1  1/153 (0.65%)  0/76 (0.00%) 
Sepsis † 1  4/153 (2.61%)  1/76 (1.32%) 
Septic shock † 1  1/153 (0.65%)  1/76 (1.32%) 
Soft tissue infection † 1  1/153 (0.65%)  0/76 (0.00%) 
Staphylococcal infection † 1  1/153 (0.65%)  0/76 (0.00%) 
Streptococcal infection † 1  0/153 (0.00%)  1/76 (1.32%) 
Upper respiratory tract infection † 1  1/153 (0.65%)  0/76 (0.00%) 
Urinary tract infection † 1  4/153 (2.61%)  1/76 (1.32%) 
Urinary tract infection bacterial † 1  0/153 (0.00%)  1/76 (1.32%) 
Urosepsis † 1  1/153 (0.65%)  1/76 (1.32%) 
Injury, poisoning and procedural complications     
Ankle fracture † 1  0/153 (0.00%)  1/76 (1.32%) 
Clavicle fracture † 1  1/153 (0.65%)  0/76 (0.00%) 
Fall † 1  7/153 (4.58%)  3/76 (3.95%) 
Femur fracture † 1  6/153 (3.92%)  0/76 (0.00%) 
Head injury † 1  1/153 (0.65%)  0/76 (0.00%) 
Hip fracture † 1  0/153 (0.00%)  3/76 (3.95%) 
Humerus fracture † 1  2/153 (1.31%)  1/76 (1.32%) 
Joint dislocation † 1  1/153 (0.65%)  0/76 (0.00%) 
Joint injury † 1  1/153 (0.65%)  0/76 (0.00%) 
Pelvic bone injury † 1  1/153 (0.65%)  0/76 (0.00%) 
Rib fracture † 1  1/153 (0.65%)  0/76 (0.00%) 
Road traffic accident † 1  1/153 (0.65%)  0/76 (0.00%) 
Spinal column injury † 1  1/153 (0.65%)  0/76 (0.00%) 
Spinal fracture † 1  1/153 (0.65%)  0/76 (0.00%) 
Subdural haematoma † 1  1/153 (0.65%)  0/76 (0.00%) 
Thoracic vertebral fracture † 1  0/153 (0.00%)  1/76 (1.32%) 
Investigations     
General physical condition abnormal † 1  1/153 (0.65%)  0/76 (0.00%) 
Metabolism and nutrition disorders     
Dehydration † 1  1/153 (0.65%)  0/76 (0.00%) 
Hypoglycaemia † 1  1/153 (0.65%)  0/76 (0.00%) 
Lactic acidosis † 1  1/153 (0.65%)  0/76 (0.00%) 
Type 2 diabetes mellitus † 1  1/153 (0.65%)  0/76 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain † 1  3/153 (1.96%)  0/76 (0.00%) 
Chondritis † 1  1/153 (0.65%)  0/76 (0.00%) 
Flank pain † 1  1/153 (0.65%)  0/76 (0.00%) 
Gouty arthritis † 1  1/153 (0.65%)  0/76 (0.00%) 
Muscle haemorrhage † 1  1/153 (0.65%)  0/76 (0.00%) 
Muscular weakness † 1  1/153 (0.65%)  0/76 (0.00%) 
Myositis † 1  1/153 (0.65%)  0/76 (0.00%) 
Polymyalgia rheumatica † 1  1/153 (0.65%)  0/76 (0.00%) 
Rheumatoid arthritis † 1  1/153 (0.65%)  0/76 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma † 1  3/153 (1.96%)  0/76 (0.00%) 
Colon adenoma † 1  1/153 (0.65%)  0/76 (0.00%) 
Intraductal papillary mucinous neoplasm † 1  1/153 (0.65%)  0/76 (0.00%) 
Myelodysplastic syndrome † 1  2/153 (1.31%)  1/76 (1.32%) 
Refractory anaemia with an excess of blasts † 1  4/153 (2.61%)  0/76 (0.00%) 
Squamous cell carcinoma † 1  1/153 (0.65%)  0/76 (0.00%) 
Squamous cell carcinoma of skin † 1  3/153 (1.96%)  0/76 (0.00%) 
Systemic mastocytosis † 1  1/153 (0.65%)  0/76 (0.00%) 
Transformation to acute myeloid leukaemia † 1  3/153 (1.96%)  1/76 (1.32%) 
Nervous system disorders     
Cerebral haemorrhage † 1  2/153 (1.31%)  0/76 (0.00%) 
Cerebral ischaemia † 1  0/153 (0.00%)  1/76 (1.32%) 
Cerebrospinal fluid leakage † 1  0/153 (0.00%)  1/76 (1.32%) 
Haemorrhage intracranial † 1  0/153 (0.00%)  1/76 (1.32%) 
Seizure † 1  1/153 (0.65%)  0/76 (0.00%) 
Syncope † 1  3/153 (1.96%)  0/76 (0.00%) 
Product Issues     
Thrombosis in device † 1  1/153 (0.65%)  0/76 (0.00%) 
Psychiatric disorders     
Confusional state † 1  1/153 (0.65%)  0/76 (0.00%) 
Delirium † 1  0/153 (0.00%)  1/76 (1.32%) 
Suicide attempt † 1  0/153 (0.00%)  1/76 (1.32%) 
Renal and urinary disorders     
Acute kidney injury † 1  2/153 (1.31%)  0/76 (0.00%) 
Renal colic † 1  1/153 (0.65%)  0/76 (0.00%) 
Renal failure † 1  1/153 (0.65%)  1/76 (1.32%) 
Urethral stenosis † 1  1/153 (0.65%)  0/76 (0.00%) 
Urinary retention † 1  1/153 (0.65%)  1/76 (1.32%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome † 1  1/153 (0.65%)  0/76 (0.00%) 
Dyspnoea † 1  2/153 (1.31%)  0/76 (0.00%) 
Dyspnoea exertional † 1  1/153 (0.65%)  0/76 (0.00%) 
Epistaxis † 1  2/153 (1.31%)  0/76 (0.00%) 
Hypoxia † 1  1/153 (0.65%)  1/76 (1.32%) 
Pulmonary fibrosis † 1  1/153 (0.65%)  0/76 (0.00%) 
Respiratory failure † 1  0/153 (0.00%)  1/76 (1.32%) 
Vascular disorders     
Aortic stenosis † 1  1/153 (0.65%)  0/76 (0.00%) 
Granulomatosis with polyangiitis † 1  1/153 (0.65%)  0/76 (0.00%) 
Orthostatic hypotension † 1  1/153 (0.65%)  0/76 (0.00%) 
Shock haemorrhagic † 1  1/153 (0.65%)  0/76 (0.00%) 
1
Term from vocabulary, MedDRA 23.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Luspatercept Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   145/153 (94.77%)   63/76 (82.89%) 
Blood and lymphatic system disorders     
Anaemia † 1  14/153 (9.15%)  6/76 (7.89%) 
Neutropenia † 1  8/153 (5.23%)  7/76 (9.21%) 
Cardiac disorders     
Palpitations † 1  11/153 (7.19%)  5/76 (6.58%) 
Tachycardia † 1  8/153 (5.23%)  0/76 (0.00%) 
Ear and labyrinth disorders     
Vertigo † 1  12/153 (7.84%)  0/76 (0.00%) 
Gastrointestinal disorders     
Abdominal pain † 1  11/153 (7.19%)  4/76 (5.26%) 
Abdominal pain upper † 1  11/153 (7.19%)  2/76 (2.63%) 
Constipation † 1  21/153 (13.73%)  7/76 (9.21%) 
Diarrhoea † 1  44/153 (28.76%)  8/76 (10.53%) 
Nausea † 1  35/153 (22.88%)  6/76 (7.89%) 
Vomiting † 1  14/153 (9.15%)  5/76 (6.58%) 
General disorders     
Asthenia † 1  40/153 (26.14%)  9/76 (11.84%) 
Fatigue † 1  46/153 (30.07%)  11/76 (14.47%) 
Influenza like illness † 1  9/153 (5.88%)  3/76 (3.95%) 
Malaise † 1  8/153 (5.23%)  3/76 (3.95%) 
Oedema peripheral † 1  37/153 (24.18%)  13/76 (17.11%) 
Pyrexia † 1  19/153 (12.42%)  6/76 (7.89%) 
Infections and infestations     
Bronchitis † 1  19/153 (12.42%)  1/76 (1.32%) 
Influenza † 1  11/153 (7.19%)  0/76 (0.00%) 
Nasopharyngitis † 1  18/153 (11.76%)  4/76 (5.26%) 
Upper respiratory tract infection † 1  19/153 (12.42%)  4/76 (5.26%) 
Urinary tract infection † 1  21/153 (13.73%)  4/76 (5.26%) 
Injury, poisoning and procedural complications     
Fall † 1  25/153 (16.34%)  7/76 (9.21%) 
Investigations     
Alanine aminotransferase increased † 1  9/153 (5.88%)  3/76 (3.95%) 
Aspartate aminotransferase increased † 1  10/153 (6.54%)  1/76 (1.32%) 
Weight decreased † 1  9/153 (5.88%)  5/76 (6.58%) 
Metabolism and nutrition disorders     
Decreased appetite † 1  14/153 (9.15%)  3/76 (3.95%) 
Hyperglycaemia † 1  12/153 (7.84%)  3/76 (3.95%) 
Hyperkalaemia † 1  10/153 (6.54%)  1/76 (1.32%) 
Hyperuricaemia † 1  12/153 (7.84%)  2/76 (2.63%) 
Iron overload † 1  9/153 (5.88%)  3/76 (3.95%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  13/153 (8.50%)  9/76 (11.84%) 
Back pain † 1  32/153 (20.92%)  6/76 (7.89%) 
Myalgia † 1  13/153 (8.50%)  5/76 (6.58%) 
Nervous system disorders     
Dizziness † 1  35/153 (22.88%)  4/76 (5.26%) 
Headache † 1  27/153 (17.65%)  5/76 (6.58%) 
Syncope † 1  10/153 (6.54%)  1/76 (1.32%) 
Psychiatric disorders     
Anxiety † 1  9/153 (5.88%)  1/76 (1.32%) 
Confusional state † 1  9/153 (5.88%)  0/76 (0.00%) 
Depression † 1  9/153 (5.88%)  5/76 (6.58%) 
Insomnia † 1  13/153 (8.50%)  4/76 (5.26%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia † 1  8/153 (5.23%)  0/76 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1  35/153 (22.88%)  10/76 (13.16%) 
Dyspnoea † 1  30/153 (19.61%)  5/76 (6.58%) 
Epistaxis † 1  12/153 (7.84%)  3/76 (3.95%) 
Oropharyngeal pain † 1  6/153 (3.92%)  6/76 (7.89%) 
Skin and subcutaneous tissue disorders     
Erythema † 1  2/153 (1.31%)  4/76 (5.26%) 
Pruritus † 1  11/153 (7.19%)  3/76 (3.95%) 
Vascular disorders     
Hypertension † 1  16/153 (10.46%)  6/76 (7.89%) 
1
Term from vocabulary, MedDRA 23.0
†
Indicates events were collected by systematic assessment
[Not Specified]
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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
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Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Phone: Please email
EMail: Clinical.Trials@bms.com
Publications of Results:
Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Diez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Gotze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellstrom-Lindberg E, Zeidan AM, Ades L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892.
Komrokji RS. Luspatercept in Myelodysplastic Syndromes: Who and When? Hematol Oncol Clin North Am. 2020 Apr;34(2):393-400. doi: 10.1016/j.hoc.2019.10.004. Epub 2020 Jan 21.
Fenaux P, Kiladjian JJ, Platzbecker U. Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis. Blood. 2019 Feb 21;133(8):790-794. doi: 10.1182/blood-2018-11-876888. Epub 2019 Jan 2.
Other Publications:
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Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02631070    
Other Study ID Numbers: ACE-536-MDS-001
2015-003454-41 ( EudraCT Number )
First Submitted: November 10, 2015
First Posted: December 15, 2015
Results First Submitted: May 1, 2020
Results First Posted: May 22, 2020
Last Update Posted: December 17, 2021