Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)
Sponsor
Celgene (Industry)
Overall Status
Completed
CT.gov ID
NCT01736683
Collaborator
(none)
74
20
6
65
3.7
0.1
Study Details
Study Description
Brief Summary
The primary objective of this study is to determine a safe, tolerable and effective dose of sotatercept that results in the greatest frequency of improvement of anemia in patients diagnosed with low- or intermediate-1 risk myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
74 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Randomized, Phase 2, Parallel, Dose-Ranging, Multicenter Study of Sotatercept for the Treatment of Patients With Anemia and Low or Intermediate-1 Risk Myelodysplastic Syndromes or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)
Actual Study Start Date
:
Nov 28, 2012
Actual Primary Completion Date
:
Apr 30, 2018
Actual Study Completion Date
:
Apr 30, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Sotatercept 0.1 mg/kg Sotatercept 0.1 mg/kg |
Drug: Sotatercept
Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.
Other Names:
|
| Experimental: Sotatercept 0.3 mg/kg Sotatercept 0.3 mg/kg |
Drug: Sotatercept
Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.
Other Names:
|
| Experimental: Sotatercept 0.5 mg/kg Sotatercept 0.5 mg/kg |
Drug: Sotatercept
Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.
Other Names:
|
| Experimental: Sotatercept 1.0 mg/kg Sotatercept 1.0 mg/kg |
Drug: Sotatercept
Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.
Other Names:
|
| Experimental: Sotatercept 1.5 mg/kg Sotatercept 1.5 mg/kg |
Drug: Sotatercept
Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.
Other Names:
|
| Experimental: Sotatercept 2.0 mg/kg Sotatercept 2.0 mg/kg |
Drug: Sotatercept
Sotatercept is supplied as a lyophilized powder that is reconstituted using Water for Injection (WFI) and administered as a subcutaneous injection (SC) injection by the study staff at the clinical site.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate) [Day 2 to Day 142]
The responder rate includes non-transfusion dependent efficacy (NTDE) participants and transfusion dependent efficacy (TDE) participants. For non-transfusion dependence efficacy (NTDE) participants who required < 4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as an increase of >=1.5 g/dL hemoglobin sustained for 56 days over a period of >=8 weeks. For transfusion dependence efficacy (TDE) participants who required >=4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as a decrease of >= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks.
Secondary Outcome Measures
- Time to Erythroid Hematological Improvement (HI-E) Response [Day 1 to Day 87]
Time to first response = start date of first response (HI-E) - first dose date + 1 day. For NTDE participants (who required < 4 units of RBCs in the 8 weeks prior to start of therapy), HI-E was defined as an increase of >=1.5 g/dL hemoglobin sustained for 56 days over a period of >=8 weeks. For TDE participants (who required >=4 units of RBCs in the 8 weeks prior to start of therapy), HI-E was defined as a decrease of >= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks.
- Duration of Erythroid Hematological Improvement (HI-E) [Day 1 to 183.7 weeks]
The duration of HI-E response for participants who responded was (the last date of the consecutive hemoglobin [Hgb] measurements of the first >=56 day interval) - (the first date of the consecutive Hgb measurements of the first >=56 day interval) + 1 day.
- Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression [Day 1 to 183.7 weeks]
Progression to AML used criteria by the International Working Group (IWG) Response Criteria in Myelodysplasia (Cheson, 2006). Progression is considered if any of the following are met: - >=50% increase in blasts - >=50% decrement from maximum remission/response levels in granulocytes or platelets - Reduction in Hgb concentration by >=2 g/dL - Transfusion dependence This outcome was defined as a Kaplan-Meier estimate however few participants progressed so a Kaplan-Meier analysis could not be performed. Disclosed are time to progression values only for participants who did progress to AML.
- Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression [Day 1 to 257.3 weeks]
Progression to events of higher risk MDS used criteria from the International Prognostic Scoring System for MDS (IPSS) which assigns a prognostic score (0=good and increasing in risk by half-grades with the top score outlined below) for three prognostic variables: - Marrow blasts (score 0-2.0) - Karyotype (score 0-1.0) - Cytopenias: neutrophil, platelets, and Hg counts (score 0-0.5) The three individual scores are summed resulting in a full range of 0- 3.5 and placed into risk categories 0 = low risk 0.5-1.0 = intermediate-1 risk 1.5-2.0 = intermediate-2 risk >=2.5 = high risk This outcome was defined as a Kaplan-Meier estimate however few participants progressed so a Kaplan-Meier analysis could not be performed. Data reported represent event times (weeks) for participants who did progress to higher risk MDS categories.
- Kaplan-Meier Estimates for Progression-free Survival [Day 1 to 257.3 weeks]
Participants who had disease progression were considered to have events. Participants who died without acute myeloid leukemia (AML) were also considered to have events with the event date as the date of death. Those who did not have disease progression and who were lost to follow-up were censored at the last known disease progression assessment date. Participants without disease progression at the last follow-up contact were censored at the date of the last follow-up contact date. Disease Progression to AML used criteria by the International Working Group (IWG) Response Criteria in Myelodysplasia (Cheson, 2006). Progression is considered if any of the following are met: - >=50% increase in blasts - >=50% decrement from maximum remission/response levels in granulocytes or platelets - Reduction in hemoglobin (Hgb) concentration by >=2 g/dL - Transfusion dependence
- Kaplan-Meier Estimates for Overall Survival (OS) [Day 1 to 257.3 weeks]
OS was defined as the time between start of treatment and the death/censored date. Participants who died (regardless of the cause of death) were considered to have an event. Participants who were alive at the end of the study, and participants who were lost to follow-up, were censored at the last date when subjects were known to be alive.
- Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints [Cycle 1 Day 8 and !5 up to Cycle 2 Day 1]
Maximum observed serum concentration, obtained directly from the observed concentration versus time data.
- Participants With Treatment-Emergent Adverse Events (TEAE) [Day 1 up to 59.2 months]
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on or after the first treatment of the study medication and within 42 days after the last dose. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0 and the scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death. Relation to study drug was determined by the investigator. A treatment-related TEAE is defined as TEAE which was considered to be related to the study drug and reported as 'Suspected' on the CRF. AEs with a missing relationship were treated as 'treatment-related' in data summaries.
- Dose Limiting Toxicities (DLTs) [Day 1 to 59.2 months]
The following were DLTs if the investigator suspected they were treatment related: 1. Increase to >= 140 mmHg systolic blood pressure 2. Increase to >=90 mmHg diastolic blood pressure 3. Increase to >=140 systolic and increase > 20 mmHg compared to baseline systolic 4. Increase to >=90 mmHg diastolic and increase > 20 mmHg compared to baseline diastolic 5. Introduction of new anti-hypertension medication during treatment 6. Increase in dose of baseline anti-hypertension medication during treatment 7. >= Grade 2 (moderate severity or worse) hypertension as an adverse event
- Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval [Day 2 to Day 142]
Number of participants who achieved RBC-independence was defined as participants who required no RBC-transfusions during a 56-day interval of erythroid hematological improvement (HI-E). NTDE = non-transfusion dependence efficacy participants who required < 4 units of RBCs in the 8 weeks prior to start of therapy TDE = transfusion dependence efficacy participants who required >=4 units of RBCs in the 8 weeks prior to start of therapy
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Men and women ≥ 18 years of age
-
Documented diagnosis of myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML), white blood cells (WBC) ≤ 13,000 /mm^3, World Health Organization (WHO) that meets International Prognostic Scoring System (IPSS) criteria for low or intermediate-1 risk disease
-
Anemia, Hemoglobin (Hgb) ≤ 9.0 g/dL or ≥ 2 units of Red Blood Cells (RBCs) within 84 days
-
No response or loss of response to Erythropoiesis-Stimulating Agents (ESAs) or erythropoetin (EPO) > 500 mU/ml
-
Eastern Cooperative Group (ECOG) score ≤2.
-
Creatinine < 1.5 * Upper Limit of the Normal (ULN)
-
Total bilirubin ≤3.0 mg/dL
-
Aspartate aminotransferase (AST)/Serum glutamic oxaloacetic transaminase (SGOT) & Alanine Aminotransferase (ALT)/Serum Glutamic Pyruvic (SGPT) ≤3.0 * Upper Limit of Norma (ULN)
-
Free of metastatic malignancy (other than MDS) for ≥2 years
-
Highly effective methods of birth control for females and males
Exclusion Criteria:
-
Chromosome 5q deletion
-
Pregnant or breast feeding women and males who do not agree to use condom during the sexual contact with females of childbearing potential
-
Major surgery within 30 days
-
Incomplete recovery or incomplete healing of wounds from previous surgery
-
Heart failure ≥3 (New York Heart Association (NYHA))
-
Thromboembolic or myocardial infarction event within 6 months
-
Concurrent anti-cancer cytotoxic chemotherapy
-
History of severe allergic or anaphylactic reaction or hypersensitivity to recombinant protein
-
Known positive for Human Immunovirus (HIV) or infectious Hepatitis type C or active infectious Hepatitis type B
-
Clinically significant anemia unrelated to MDS
-
Thrombocytopenia (<30,000/uL)
-
Uncontrolled hypertension
-
Treatment with another investigational drug or device within 28 days prior to Day 1
-
Prior exposure to sotatercept (ACE-011)
-
Any serious medical condition, lab abnormality or psychiatric illness
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rocky Mountain Cancer Center-Midtown | Denver | Colorado | United States | 80218 |
| 2 | H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | United States | 33612 |
| 3 | Johns Hopkins | Baltimore | Maryland | United States | 21231 |
| 4 | Dana-Farber / Harvard Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 5 | Monter Cancer Center, North Shore LIJ Health Systems | Lake Success | New York | United States | 11042 |
| 6 | Columbia University Medical Center/New York-Presbyterian Hospital | New York | New York | United States | 10032 |
| 7 | The Cleveland Clinic Foundation Hematology and Medical Oncology Rm 35 | Cleveland | Ohio | United States | 44195 |
| 8 | Sarah Cannon Research Inst | Nashville | Tennessee | United States | 37203 |
| 9 | Texas Oncology Round Rock Cancer Center - Round Rock | Round Rock | Texas | United States | 78681 |
| 10 | University of Texas Health Science Center at San Antonio | San Antonio | Texas | United States | 78229 |
| 11 | Texas Oncology, P.A. - Tyler | Tyler | Texas | United States | 75702 |
| 12 | Virginia Oncology Associates | Norfolk | Virginia | United States | 23502 |
| 13 | Yakima Valley Memorial Hospital/ North Star Lodge | Yakima | Washington | United States | 98902 |
| 14 | Centre Hospitalier Universitaire d'Avicennes | Bobigny Cedex | France | 93009 | |
| 15 | Institute Paoli-Calmettes Service Haematology | Bp 156, | France | 13273 | |
| 16 | CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang | Lille | France | 59037 | |
| 17 | CHRU Nantes | Nantes | France | 44093 | |
| 18 | Hopital Cochin Hematologie | Paris Cedex 14 | France | 75679 | |
| 19 | Centre Henri Becquerel | Rouen | France | 79038 | |
| 20 | CHU Purpan | Toulouse | France | 31059 |
Sponsors and Collaborators
- Celgene
Investigators
- Study Director: Rodrigo Ito, MD, Celgene Corporation
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT01736683
Other Study ID Numbers:
- ACE-011-MDS-001
- 2012-002601-22
First Posted:
Nov 29, 2012
Last Update Posted:
Jun 25, 2019
Last Verified:
Jun 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Celgene
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were stratified by concentration of serum erythropoietin (EPO) (<500 versus ≥500 IU/L), by number of transfusions within 56 days of study enrollment (<4 versus ≥4 units of red blood cells) and assigned randomly to 0.1 mg/kg and 0.3 mg/kg arms. |
|---|---|
| Pre-assignment Detail | Enrollment in the other arms (sotatercept 0.5, 1.0 and 2.0 mg/kg arms) commenced after the Steering Committee approved the higher doses based on the safety of preceding doses. |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Period Title: Overall Study | |||||
| STARTED | 7 | 6 | 21 | 35 | 5 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 7 | 6 | 21 | 35 | 5 |
Baseline Characteristics
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. | Total of all reporting groups |
| Overall Participants | 7 | 6 | 21 | 35 | 5 | 74 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
67
(8.3)
|
75
(6.9)
|
69
(8.0)
|
71
(8.2)
|
69
(13.0)
|
70
(8.4)
|
| Age, Customized (Count of Participants) | ||||||
| <65 years |
3
42.9%
|
0
0%
|
7
33.3%
|
6
17.1%
|
1
20%
|
17
23%
|
| >=65 - <75 years |
2
28.6%
|
3
50%
|
8
38.1%
|
17
48.6%
|
2
40%
|
32
43.2%
|
| >=75 years |
2
28.6%
|
3
50%
|
6
28.6%
|
12
34.3%
|
2
40%
|
25
33.8%
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
3
42.9%
|
0
0%
|
4
19%
|
17
48.6%
|
4
80%
|
28
37.8%
|
| Male |
4
57.1%
|
6
100%
|
17
81%
|
18
51.4%
|
1
20%
|
46
62.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
2
9.5%
|
0
0%
|
0
0%
|
2
2.7%
|
| Not Hispanic or Latino |
7
100%
|
6
100%
|
13
61.9%
|
19
54.3%
|
4
80%
|
49
66.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
6
28.6%
|
16
45.7%
|
1
20%
|
23
31.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
1
1.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
1
2.9%
|
0
0%
|
1
1.4%
|
| White |
7
100%
|
6
100%
|
14
66.7%
|
18
51.4%
|
3
60%
|
48
64.9%
|
| More than one race |
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
NA
NaN
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
7
33.3%
|
16
45.7%
|
1
20%
|
24
32.4%
|
| Region of Enrollment (Count of Participants) | ||||||
| United States |
7
100%
|
6
100%
|
15
71.4%
|
18
51.4%
|
4
80%
|
50
67.6%
|
| France |
0
0%
|
0
0%
|
6
28.6%
|
17
48.6%
|
1
20%
|
24
32.4%
|
| Height (meters) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [meters] |
1.70
(0.110)
|
1.75
(0.054)
|
1.70
(0.093)
|
1.68
(0.089)
|
1.56
(0.043)
|
1.68
(0.095)
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [kg] |
85.3
(21.79)
|
79.5
(13.90)
|
77.9
(13.97)
|
73.5
(15.55)
|
56.4
(7.25)
|
75.2
(16.14)
|
| Erythropoietin level (Count of Participants) | ||||||
| <=200 mIU/mL |
2
28.6%
|
3
50%
|
6
28.6%
|
16
45.7%
|
2
40%
|
29
39.2%
|
| >200 to <=500 mIU/mL |
2
28.6%
|
1
16.7%
|
6
28.6%
|
6
17.1%
|
0
0%
|
15
20.3%
|
| >500 mIU/mL |
3
42.9%
|
2
33.3%
|
9
42.9%
|
9
25.7%
|
2
40%
|
25
33.8%
|
| Missing |
0
0%
|
0
0%
|
0
0%
|
4
11.4%
|
1
20%
|
5
6.8%
|
| Red Blood Cell (RBC) Transfusion Burden Categories (Count of Participants) | ||||||
| < 4 units (Low Transfusion Burden) |
0
0%
|
0
0%
|
3
14.3%
|
8
22.9%
|
1
20%
|
12
16.2%
|
| >= 4 units (High Transfusion Burden) |
7
100%
|
6
100%
|
18
85.7%
|
27
77.1%
|
4
80%
|
62
83.8%
|
| Number of Previous Erythropoiesis-Stimulating Agents (ESA) Therapies for Myelodysplastic Syndromes (Count of Participants) | ||||||
| 0 ESA therapies |
1
14.3%
|
0
0%
|
1
4.8%
|
0
0%
|
0
0%
|
2
2.7%
|
| 1 ESA therapy |
6
85.7%
|
2
33.3%
|
11
52.4%
|
23
65.7%
|
3
60%
|
45
60.8%
|
| 2 ESA therapies |
0
0%
|
4
66.7%
|
8
38.1%
|
10
28.6%
|
2
40%
|
24
32.4%
|
| 3 ESA therapies |
0
0%
|
0
0%
|
1
4.8%
|
2
5.7%
|
0
0%
|
3
4.1%
|
| Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS) (Count of Participants) | ||||||
| 0 non-ESA agents |
0
0%
|
0
0%
|
2
9.5%
|
7
20%
|
2
40%
|
11
14.9%
|
| 1 non-ESA agent |
1
14.3%
|
0
0%
|
7
33.3%
|
16
45.7%
|
1
20%
|
25
33.8%
|
| 2 non-ESA agents |
2
28.6%
|
1
16.7%
|
6
28.6%
|
7
20%
|
1
20%
|
17
23%
|
| 3 non-ESA agents |
2
28.6%
|
1
16.7%
|
2
9.5%
|
2
5.7%
|
1
20%
|
8
10.8%
|
| 4 non-ESA agents |
0
0%
|
1
16.7%
|
2
9.5%
|
3
8.6%
|
0
0%
|
6
8.1%
|
| 5 non-ESA agents |
1
14.3%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
2
2.7%
|
| >5 non-ESA agents |
1
14.3%
|
2
33.3%
|
2
9.5%
|
0
0%
|
0
0%
|
5
6.8%
|
| International Prognostic Scoring System (IPSS) Risk Category (Count of Participants) | ||||||
| Low - 0 |
4
57.1%
|
4
66.7%
|
5
23.8%
|
11
31.4%
|
0
0%
|
24
32.4%
|
| Intermediate- 1: 0.5 to 1 |
3
42.9%
|
2
33.3%
|
16
76.2%
|
24
68.6%
|
5
100%
|
50
67.6%
|
| Intermediate- 2: 1.5 to 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| High: >= 2.5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Erythropoietin Level (Count of Participants) | ||||||
| <=200 mIU/mL |
2
28.6%
|
3
50%
|
6
28.6%
|
16
45.7%
|
2
40%
|
29
39.2%
|
| >200 to <=500 mIU/mL |
2
28.6%
|
1
16.7%
|
6
28.6%
|
6
17.1%
|
0
0%
|
15
20.3%
|
| >500 mIU/mL |
3
42.9%
|
2
33.3%
|
9
42.9%
|
9
25.7%
|
2
40%
|
25
33.8%
|
| Missing |
0
0%
|
0
0%
|
0
0%
|
4
11.4%
|
1
20%
|
5
6.8%
|
Outcome Measures
| Title | Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate) |
|---|---|
| Description | The responder rate includes non-transfusion dependent efficacy (NTDE) participants and transfusion dependent efficacy (TDE) participants. For non-transfusion dependence efficacy (NTDE) participants who required < 4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as an increase of >=1.5 g/dL hemoglobin sustained for 56 days over a period of >=8 weeks. For transfusion dependence efficacy (TDE) participants who required >=4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as a decrease of >= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks. |
| Time Frame | Day 2 to Day 142 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population: all participants who take at least one dose of study medication and have baseline and at least one post-baseline assessment of efficacy without major deviation from protocol. |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 7 | 6 | 21 | 35 | 5 |
| All participants |
0
0%
|
66.7
1111.7%
|
42.9
204.3%
|
60.0
171.4%
|
40.0
800%
|
| NTDE subpopulation |
33.3
475.7%
|
62.5
1041.7%
|
100
476.2%
|
||
| TDE subpopulation |
0
0%
|
66.7
1111.7%
|
44.4
211.4%
|
59.3
169.4%
|
25.0
500%
|
| Title | Time to Erythroid Hematological Improvement (HI-E) Response |
|---|---|
| Description | Time to first response = start date of first response (HI-E) - first dose date + 1 day. For NTDE participants (who required < 4 units of RBCs in the 8 weeks prior to start of therapy), HI-E was defined as an increase of >=1.5 g/dL hemoglobin sustained for 56 days over a period of >=8 weeks. For TDE participants (who required >=4 units of RBCs in the 8 weeks prior to start of therapy), HI-E was defined as a decrease of >= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks. |
| Time Frame | Day 1 to Day 87 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population of participants who responded |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 0 | 4 | 9 | 21 | 2 |
| All participants |
24.0
|
1.0
|
1.0
|
48
|
|
| NTDE subpopulation |
1.0
|
1.0
|
9.0
|
||
| TDE subpopulation |
24.0
|
1.5
|
1.5
|
87
|
| Title | Duration of Erythroid Hematological Improvement (HI-E) |
|---|---|
| Description | The duration of HI-E response for participants who responded was (the last date of the consecutive hemoglobin [Hgb] measurements of the first >=56 day interval) - (the first date of the consecutive Hgb measurements of the first >=56 day interval) + 1 day. |
| Time Frame | Day 1 to 183.7 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population of participants who responded |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 0 | 4 | 9 | 21 | 2 |
| All participants |
62.5
|
104.0
|
133.0
|
96.0
|
|
| NTDE subpopulation |
79.0
|
1043.0
|
134.0
|
||
| TDE subpopulation |
62.5
|
105.5
|
96.5
|
58.0
|
| Title | Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression |
|---|---|
| Description | Progression to AML used criteria by the International Working Group (IWG) Response Criteria in Myelodysplasia (Cheson, 2006). Progression is considered if any of the following are met: - >=50% increase in blasts - >=50% decrement from maximum remission/response levels in granulocytes or platelets - Reduction in Hgb concentration by >=2 g/dL - Transfusion dependence This outcome was defined as a Kaplan-Meier estimate however few participants progressed so a Kaplan-Meier analysis could not be performed. Disclosed are time to progression values only for participants who did progress to AML. |
| Time Frame | Day 1 to 183.7 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population of participants who progressed to AML |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 0 | 0 | 1 | 1 | 0 |
| Number [weeks] |
45.6
|
78.0
|
| Title | Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression |
|---|---|
| Description | Progression to events of higher risk MDS used criteria from the International Prognostic Scoring System for MDS (IPSS) which assigns a prognostic score (0=good and increasing in risk by half-grades with the top score outlined below) for three prognostic variables: - Marrow blasts (score 0-2.0) - Karyotype (score 0-1.0) - Cytopenias: neutrophil, platelets, and Hg counts (score 0-0.5) The three individual scores are summed resulting in a full range of 0- 3.5 and placed into risk categories 0 = low risk 0.5-1.0 = intermediate-1 risk 1.5-2.0 = intermediate-2 risk >=2.5 = high risk This outcome was defined as a Kaplan-Meier estimate however few participants progressed so a Kaplan-Meier analysis could not be performed. Data reported represent event times (weeks) for participants who did progress to higher risk MDS categories. |
| Time Frame | Day 1 to 257.3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population of participants who progressed to high risk MDS categories |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 1 | 0 | 1 | 1 | 0 |
| Number [weeks] |
15.1
|
24.7
|
67.4
|
| Title | Kaplan-Meier Estimates for Progression-free Survival |
|---|---|
| Description | Participants who had disease progression were considered to have events. Participants who died without acute myeloid leukemia (AML) were also considered to have events with the event date as the date of death. Those who did not have disease progression and who were lost to follow-up were censored at the last known disease progression assessment date. Participants without disease progression at the last follow-up contact were censored at the date of the last follow-up contact date. Disease Progression to AML used criteria by the International Working Group (IWG) Response Criteria in Myelodysplasia (Cheson, 2006). Progression is considered if any of the following are met: - >=50% increase in blasts - >=50% decrement from maximum remission/response levels in granulocytes or platelets - Reduction in hemoglobin (Hgb) concentration by >=2 g/dL - Transfusion dependence |
| Time Frame | Day 1 to 257.3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 7 | 6 | 21 | 35 | 5 |
| Median (95% Confidence Interval) [weeks] |
82.7
|
NA
|
NA
|
NA
|
NA
|
| Title | Kaplan-Meier Estimates for Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time between start of treatment and the death/censored date. Participants who died (regardless of the cause of death) were considered to have an event. Participants who were alive at the end of the study, and participants who were lost to follow-up, were censored at the last date when subjects were known to be alive. |
| Time Frame | Day 1 to 257.3 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 7 | 6 | 21 | 35 | 5 |
| Median (95% Confidence Interval) [weeks] |
82.7
|
NA
|
NA
|
NA
|
NA
|
| Title | Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints |
|---|---|
| Description | Maximum observed serum concentration, obtained directly from the observed concentration versus time data. |
| Time Frame | Cycle 1 Day 8 and !5 up to Cycle 2 Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic (PK) population includes participants with a sufficient amount of post-dose quantifiable PK sotatercept profile. |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/ kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/ kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 7 | 6 | 21 | 35 | 5 |
| Cycle 1 Day 8 |
288.06
(70.94)
|
1426.00
(27.76)
|
2237.46
(40.77)
|
6525.37
(28.31)
|
12886.14
(30.47)
|
| Cycle 1 Day 15 |
240.31
(75.32)
|
1207.68
(16.14)
|
1869.52
(36.97)
|
5149.74
(36.04)
|
8303.73
(43.57)
|
| Cycle 2 Day 1 |
252.20
(28.43)
|
957.58
(18.63)
|
1323.91
(44.40)
|
3467.58
(57.06)
|
5329.63
(38.27)
|
| Title | Participants With Treatment-Emergent Adverse Events (TEAE) |
|---|---|
| Description | An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening on or after the first treatment of the study medication and within 42 days after the last dose. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0 and the scale: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death. Relation to study drug was determined by the investigator. A treatment-related TEAE is defined as TEAE which was considered to be related to the study drug and reported as 'Suspected' on the CRF. AEs with a missing relationship were treated as 'treatment-related' in data summaries. |
| Time Frame | Day 1 up to 59.2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population: all participants who receive at least one dose of study medication. |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 7 | 6 | 21 | 35 | 5 |
| >= 1 Treatment-emergent adverse event (TEAE) |
6
85.7%
|
4
66.7%
|
20
95.2%
|
34
97.1%
|
5
100%
|
| >=1 Treatment-related TEAE |
2
28.6%
|
3
50%
|
7
33.3%
|
18
51.4%
|
4
80%
|
| >=1 Serious TEAE |
1
14.3%
|
2
33.3%
|
6
28.6%
|
10
28.6%
|
2
40%
|
| >=1 Serious TEAE related to treatment |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
20%
|
| >=1 TEAE severity 3 or 4 |
1
14.3%
|
2
33.3%
|
9
42.9%
|
13
37.1%
|
2
40%
|
| >=1 TEAE severity grade 3/4 related to treatment |
0
0%
|
0
0%
|
1
4.8%
|
0
0%
|
1
20%
|
| >=1 TEAE leading to death |
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
| >=1 TEAE leading to dose reduction |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| >=1 TEAE leading to dose interruption |
0
0%
|
1
16.7%
|
2
9.5%
|
9
25.7%
|
1
20%
|
| >=1 TEAE leading to dose interruption + reduction |
0
0%
|
0
0%
|
0
0%
|
1
2.9%
|
0
0%
|
| >= 1 TEAE leading to drug discontinuation |
0
0%
|
2
33.3%
|
2
9.5%
|
3
8.6%
|
2
40%
|
| Title | Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | The following were DLTs if the investigator suspected they were treatment related: 1. Increase to >= 140 mmHg systolic blood pressure 2. Increase to >=90 mmHg diastolic blood pressure 3. Increase to >=140 systolic and increase > 20 mmHg compared to baseline systolic 4. Increase to >=90 mmHg diastolic and increase > 20 mmHg compared to baseline diastolic 5. Introduction of new anti-hypertension medication during treatment 6. Increase in dose of baseline anti-hypertension medication during treatment 7. >= Grade 2 (moderate severity or worse) hypertension as an adverse event |
| Time Frame | Day 1 to 59.2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 7 | 6 | 21 | 35 | 5 |
| 1. Increase to >= 140 mmHg systolic |
1
14.3%
|
1
16.7%
|
8
38.1%
|
19
54.3%
|
2
40%
|
| 2. Increase to >=90 mmHg diastolic |
0
0%
|
0
0%
|
2
9.5%
|
2
5.7%
|
1
20%
|
| 3. =140 systolic and increase > 20 mmHg base |
0
0%
|
1
16.7%
|
5
23.8%
|
10
28.6%
|
2
40%
|
| 4. >=90 mmHg diastolic and increase > 20 mmHg base |
0
0%
|
0
0%
|
2
9.5%
|
2
5.7%
|
1
20%
|
| 5. Introduction of new anti-hypertension med |
0
0%
|
0
0%
|
4
19%
|
3
8.6%
|
1
20%
|
| 6. Incre in dose of baseline anti-hypertension med |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 7.>= Grade 2 hypertension TEAE |
0
0%
|
1
16.7%
|
2
9.5%
|
4
11.4%
|
1
20%
|
| Title | Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval |
|---|---|
| Description | Number of participants who achieved RBC-independence was defined as participants who required no RBC-transfusions during a 56-day interval of erythroid hematological improvement (HI-E). NTDE = non-transfusion dependence efficacy participants who required < 4 units of RBCs in the 8 weeks prior to start of therapy TDE = transfusion dependence efficacy participants who required >=4 units of RBCs in the 8 weeks prior to start of therapy |
| Time Frame | Day 2 to Day 142 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Evaluable Population |
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. |
| Measure Participants | 7 | 6 | 21 | 35 | 5 |
| All participants |
0
0%
|
1
16.7%
|
3
14.3%
|
15
42.9%
|
1
20%
|
| NTDE subpopulation |
1
14.3%
|
6
100%
|
1
4.8%
|
||
| TDE subpopulation |
0
0%
|
1
16.7%
|
2
9.5%
|
9
25.7%
|
0
0%
|
Adverse Events
| Time Frame | Day 1 up to 60.7 months | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg | |||||
| Arm/Group Description | Sotatercept 0.1 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.3 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to either the 0.1 mg/kg arm or the 0.3 mg/kg arm. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/5 subjects in Cycle 1 in the 0.1 mg/kg and 0.3 mg/kg treatment groups, the 0.5 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 0.5 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 0.5 mg/ kg treatment group, the 1.0 mg/kg treatment group began inclusion in the randomization scheme. | Sotatercept 1.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. Based upon the occurrence of dose-limiting toxicity (DLT) in ≤ 1/6 subjects in Cycle 1 in the 1.0 mg/ kg treatment group, the 2.0 mg/kg treatment group began inclusion in the randomization scheme. Following evaluation of all treatment group data by the Steering Committee, enrollment continued only in the 1.0 mg/kg arm because the arm had the greatest frequency of erythroid hematological improvement (HI-E). | Sotatercept 2.0 mg/kg administered via subcutaneous injection every third week (Q3W). Participants were randomized to one of the active treatment arms. Efficacy and safety data were assessed by a Steering Committee. The 2.0 mg/kg sotatercept dose was reduced to 1.5 mg/kg for ongoing and newly enrolled participants by protocol amendment. | |||||
All Cause Mortality |
||||||||||
| Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/7 (14.3%) | 1/6 (16.7%) | 6/21 (28.6%) | 6/35 (17.1%) | 1/5 (20%) | |||||
Serious Adverse Events |
||||||||||
| Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/7 (14.3%) | 2/6 (33.3%) | 6/21 (28.6%) | 10/35 (28.6%) | 2/5 (40%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 1/5 (20%) | |||||
| Cardiac disorders | ||||||||||
| Angina pectoris | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Colitis | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Large intestine perforation | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| General disorders | ||||||||||
| Mass | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Non-cardiac chest pain | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Pyrexia | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholangitis | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Cholelithiasis | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Infections and infestations | ||||||||||
| Bronchitis | 1/7 (14.3%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Clostridium difficile colitis | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Escherichia pyelonephritis | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Influenza | 1/7 (14.3%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Lung infection | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Peritoneal abscess | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Pneumonia | 0/7 (0%) | 1/6 (16.7%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Hip fracture | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 0/35 (0%) | 0/5 (0%) | |||||
| Spinal compression fracture | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Spinal fracture | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Subdural haematoma | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Transfusion reaction | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 1/5 (20%) | |||||
| Investigations | ||||||||||
| Blood pressure increased | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 1/5 (20%) | |||||
| International normalised ratio increased | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Osteoarthritis | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Basal cell carcinoma | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Nervous system disorders | ||||||||||
| Cerebrovascular accident | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Hemiparesis | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Delirium | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Haematuria | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Hypoxia | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Diabetic foot | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Vascular disorders | ||||||||||
| Aortic stenosis | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Hypotension | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Sotatercept 0.1 mg/kg | Sotatercept 0.3 mg/kg | Sotatercept 0.5 mg/kg | Sotatercept 1.0 mg/kg | Sotatercept 2.0 mg/kg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/7 (85.7%) | 4/6 (66.7%) | 18/21 (85.7%) | 32/35 (91.4%) | 5/5 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Haemolytic anaemia | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Leukocytosis | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Neutropenia | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 1/35 (2.9%) | 1/5 (20%) | |||||
| Thrombocytopenia | 1/7 (14.3%) | 0/6 (0%) | 2/21 (9.5%) | 1/35 (2.9%) | 1/5 (20%) | |||||
| Cardiac disorders | ||||||||||
| Sinus tachycardia | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 1/5 (20%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Ear pain | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Vertigo | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Eye disorders | ||||||||||
| Eye haemorrhage | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Eye inflammation | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 1/5 (20%) | |||||
| Eyelid oedema | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Lacrimation increased | 0/7 (0%) | 1/6 (16.7%) | 2/21 (9.5%) | 0/35 (0%) | 0/5 (0%) | |||||
| Vitreous floaters | 1/7 (14.3%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal discomfort | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Abdominal pain | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 5/35 (14.3%) | 0/5 (0%) | |||||
| Abdominal pain upper | 1/7 (14.3%) | 0/6 (0%) | 0/21 (0%) | 4/35 (11.4%) | 0/5 (0%) | |||||
| Constipation | 0/7 (0%) | 1/6 (16.7%) | 6/21 (28.6%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Diarrhoea | 0/7 (0%) | 2/6 (33.3%) | 7/21 (33.3%) | 9/35 (25.7%) | 2/5 (40%) | |||||
| Dry mouth | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 1/5 (20%) | |||||
| Dyspepsia | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Nausea | 0/7 (0%) | 1/6 (16.7%) | 4/21 (19%) | 8/35 (22.9%) | 2/5 (40%) | |||||
| Salivary gland enlargement | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Stomatitis | 1/7 (14.3%) | 1/6 (16.7%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Toothache | 1/7 (14.3%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Vomiting | 0/7 (0%) | 1/6 (16.7%) | 3/21 (14.3%) | 9/35 (25.7%) | 1/5 (20%) | |||||
| General disorders | ||||||||||
| Asthenia | 0/7 (0%) | 1/6 (16.7%) | 3/21 (14.3%) | 7/35 (20%) | 0/5 (0%) | |||||
| Chest discomfort | 1/7 (14.3%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Face oedema | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Fatigue | 0/7 (0%) | 1/6 (16.7%) | 6/21 (28.6%) | 11/35 (31.4%) | 1/5 (20%) | |||||
| Gait disturbance | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Influenza like illness | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Injection site reaction | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Oedema | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 1/5 (20%) | |||||
| Oedema peripheral | 2/7 (28.6%) | 2/6 (33.3%) | 6/21 (28.6%) | 11/35 (31.4%) | 0/5 (0%) | |||||
| Peripheral swelling | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 1/5 (20%) | |||||
| Pyrexia | 0/7 (0%) | 1/6 (16.7%) | 4/21 (19%) | 1/35 (2.9%) | 1/5 (20%) | |||||
| Vessel puncture site swelling | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Immune system disorders | ||||||||||
| Anaphylactic reaction | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Infections and infestations | ||||||||||
| Bronchitis | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Laryngitis | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 1/5 (20%) | |||||
| Nasopharyngitis | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Pharyngitis | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Pneumonia | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Sinusitis | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 4/35 (11.4%) | 0/5 (0%) | |||||
| Tooth infection | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Upper respiratory tract infection | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 5/35 (14.3%) | 0/5 (0%) | |||||
| Urinary tract infection | 1/7 (14.3%) | 0/6 (0%) | 0/21 (0%) | 4/35 (11.4%) | 2/5 (40%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Contusion | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Fall | 0/7 (0%) | 2/6 (33.3%) | 1/21 (4.8%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Muscle strain | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Skin abrasion | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Spinal compression fracture | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Tooth fracture | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Investigations | ||||||||||
| Alanine aminotransferase increased | 0/7 (0%) | 0/6 (0%) | 3/21 (14.3%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Aspartate aminotransferase increased | 0/7 (0%) | 0/6 (0%) | 4/21 (19%) | 5/35 (14.3%) | 0/5 (0%) | |||||
| Blood alkaline phosphatase increased | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Blood bilirubin increased | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Blood creatinine increased | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 3/35 (8.6%) | 1/5 (20%) | |||||
| Creatinine renal clearance decreased | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Lipase increased | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Neutrophil count decreased | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 1/5 (20%) | |||||
| Platelet count decreased | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 0/35 (0%) | 1/5 (20%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 0/7 (0%) | 0/6 (0%) | 4/21 (19%) | 8/35 (22.9%) | 1/5 (20%) | |||||
| Dehydration | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Hypercalcaemia | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Hyperglycaemia | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Hyperkalaemia | 0/7 (0%) | 1/6 (16.7%) | 2/21 (9.5%) | 2/35 (5.7%) | 1/5 (20%) | |||||
| Hyperuricaemia | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Hypoglycaemia | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Iron overload | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 2/35 (5.7%) | 1/5 (20%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 4/35 (11.4%) | 0/5 (0%) | |||||
| Arthritis | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 0/35 (0%) | 1/5 (20%) | |||||
| Back pain | 1/7 (14.3%) | 1/6 (16.7%) | 1/21 (4.8%) | 4/35 (11.4%) | 1/5 (20%) | |||||
| Muscle spasms | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Muscular weakness | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Musculoskeletal chest pain | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Myalgia | 0/7 (0%) | 1/6 (16.7%) | 2/21 (9.5%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Neck pain | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 1/35 (2.9%) | 1/5 (20%) | |||||
| Osteoarthritis | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Osteopenia | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Pain in extremity | 0/7 (0%) | 1/6 (16.7%) | 3/21 (14.3%) | 4/35 (11.4%) | 1/5 (20%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Basal cell carcinoma | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Nervous system disorders | ||||||||||
| Ataxia | 1/7 (14.3%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Dizziness | 1/7 (14.3%) | 2/6 (33.3%) | 1/21 (4.8%) | 6/35 (17.1%) | 2/5 (40%) | |||||
| Dysgeusia | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Headache | 3/7 (42.9%) | 1/6 (16.7%) | 4/21 (19%) | 5/35 (14.3%) | 1/5 (20%) | |||||
| Paraesthesia | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 4/35 (11.4%) | 0/5 (0%) | |||||
| Confusional state | 0/7 (0%) | 1/6 (16.7%) | 1/21 (4.8%) | 0/35 (0%) | 0/5 (0%) | |||||
| Depression | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Insomnia | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Pollakiuria | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 0/35 (0%) | 0/5 (0%) | |||||
| Proteinuria | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Gynaecomastia | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 1/7 (14.3%) | 1/6 (16.7%) | 2/21 (9.5%) | 6/35 (17.1%) | 1/5 (20%) | |||||
| Dyspnoea | 0/7 (0%) | 1/6 (16.7%) | 6/21 (28.6%) | 2/35 (5.7%) | 1/5 (20%) | |||||
| Dyspnoea exertional | 0/7 (0%) | 1/6 (16.7%) | 1/21 (4.8%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Epistaxis | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 8/35 (22.9%) | 1/5 (20%) | |||||
| Hypoxia | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 0/35 (0%) | 0/5 (0%) | |||||
| Nasal congestion | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Rhinorrhoea | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 1/5 (20%) | |||||
| Upper-airway cough syndrome | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Dry skin | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 0/35 (0%) | 1/5 (20%) | |||||
| Ecchymosis | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Pruritus | 1/7 (14.3%) | 1/6 (16.7%) | 1/21 (4.8%) | 4/35 (11.4%) | 0/5 (0%) | |||||
| Pruritus generalised | 0/7 (0%) | 0/6 (0%) | 0/21 (0%) | 2/35 (5.7%) | 0/5 (0%) | |||||
| Rash | 0/7 (0%) | 0/6 (0%) | 2/21 (9.5%) | 3/35 (8.6%) | 0/5 (0%) | |||||
| Skin lesion | 0/7 (0%) | 1/6 (16.7%) | 0/21 (0%) | 1/35 (2.9%) | 0/5 (0%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 0/7 (0%) | 1/6 (16.7%) | 2/21 (9.5%) | 4/35 (11.4%) | 1/5 (20%) | |||||
| Hypotension | 0/7 (0%) | 0/6 (0%) | 1/21 (4.8%) | 3/35 (8.6%) | 0/5 (0%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.
Results Point of Contact
| Name/Title | Anne McClain, Senior Manager, Clinical Trial Disclosure |
|---|---|
| Organization | Celgene Corporation |
| Phone | 888-260-1599 |
| ClinicalTrialDisclosure@Celgene.com |
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT01736683
Other Study ID Numbers:
- ACE-011-MDS-001
- 2012-002601-22
First Posted:
Nov 29, 2012
Last Update Posted:
Jun 25, 2019
Last Verified:
Jun 1, 2019