Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| ACE-011-MDS-001 | Other Identifier | Celgene | |
| 2012-002601-22 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sotatercept 0.1 mg/kg | Experimental | Sotatercept 0.1 mg/kg |
|
| Sotatercept 0.3 mg/kg | Experimental | Sotatercept 0.3 mg/kg |
|
| Sotatercept 0.5 mg/kg | Experimental | Sotatercept 0.5 mg/kg |
|
| Sotatercept 1.0 mg/kg | Experimental | Sotatercept 1.0 mg/kg |
|
| Sotatercept 1.5 mg/kg | Experimental | Sotatercept 1.5 mg/kg |
|
| Sotatercept 2.0 mg/kg | Experimental | Sotatercept 2.0 mg/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sotatercept | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate) | 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. | Day 2 to Day 142 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Erythroid Hematological Improvement (HI-E) Response | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Rodrigo Ito, MD | Celgene Corporation | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rocky Mountain Cancer Center-Midtown | Denver | Colorado | 80218 | United States | ||
| H. Lee Moffitt Cancer Center and Research Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29331635 | Derived | Komrokji R, Garcia-Manero G, Ades L, Prebet T, Steensma DP, Jurcic JG, Sekeres MA, Berdeja J, Savona MR, Beyne-Rauzy O, Stamatoullas A, DeZern AE, Delaunay J, Borthakur G, Rifkin R, Boyd TE, Laadem A, Vo B, Zhang J, Puccio-Pick M, Attie KM, Fenaux P, List AF. Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial. Lancet Haematol. 2018 Feb;5(2):e63-e72. doi: 10.1016/S2352-3026(18)30002-4. Epub 2018 Jan 10. |
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Sotatercept 0.1 mg/kg | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 4, 2015 | Apr 30, 2019 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Day 1 to Day 87 |
| Duration of Erythroid Hematological Improvement (HI-E) | 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. | Day 1 to 183.7 weeks |
| Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression | 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. | Day 1 to 183.7 weeks |
| Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression | 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. | Day 1 to 257.3 weeks |
| Kaplan-Meier Estimates for Progression-free Survival | 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 | Day 1 to 257.3 weeks |
| Kaplan-Meier Estimates for Overall Survival (OS) | 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. | Day 1 to 257.3 weeks |
| Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints | Maximum observed serum concentration, obtained directly from the observed concentration versus time data. | Cycle 1 Day 8 and !5 up to Cycle 2 Day 1 |
| Participants With Treatment-Emergent Adverse Events (TEAE) | 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. | Day 1 up to 59.2 months |
| Dose Limiting Toxicities (DLTs) | 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 | Day 1 to 59.2 months |
| Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval | 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 | Day 2 to Day 142 |
| Tampa |
| Florida |
| 33612 |
| United States |
| Johns Hopkins | Baltimore | Maryland | 21231 | United States |
| Dana-Farber / Harvard Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Monter Cancer Center, North Shore LIJ Health Systems | Lake Success | New York | 11042 | United States |
| Columbia University Medical Center/New York-Presbyterian Hospital | New York | New York | 10032 | United States |
| The Cleveland Clinic Foundation Hematology and Medical Oncology Rm 35 | Cleveland | Ohio | 44195 | United States |
| Sarah Cannon Research Inst | Nashville | Tennessee | 37203 | United States |
| Texas Oncology Round Rock Cancer Center - Round Rock | Round Rock | Texas | 78681 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78229 | United States |
| Texas Oncology, P.A. - Tyler | Tyler | Texas | 75702 | United States |
| Virginia Oncology Associates | Norfolk | Virginia | 23502 | United States |
| Yakima Valley Memorial Hospital/ North Star Lodge | Yakima | Washington | 98902 | United States |
| Centre Hospitalier Universitaire d'Avicennes | Bobigny | 93009 | France |
| Institute Paoli-Calmettes Service Haematology | BP 156, | 13273 | France |
| CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang | Lille | 59037 | France |
| CHRU Nantes | Nantes | 44093 | France |
| Hopital Cochin Hematologie | Paris | 75679 | France |
| Centre Henri Becquerel | Rouen | 79038 | France |
| CHU Purpan | Toulouse | 31059 | France |
| FG001 | Sotatercept 0.3 mg/kg | 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. |
| FG002 | Sotatercept 0.5 mg/kg | 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. |
| FG003 | Sotatercept 1.0 mg/kg | 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). |
| FG004 | Sotatercept 2.0 mg/kg | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
All randomized participants
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Sotatercept 0.1 mg/kg | 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. |
| BG001 | Sotatercept 0.3 mg/kg | 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. |
| BG002 | Sotatercept 0.5 mg/kg | 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. |
| BG003 | Sotatercept 1.0 mg/kg | 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). |
| BG004 | Sotatercept 2.0 mg/kg | 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. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Age, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Height | Mean | Standard Deviation | meters |
| |||||||||||||||
| Weight | Mean | Standard Deviation | kg |
| |||||||||||||||
| Erythropoietin level | Count of Participants | Participants |
| ||||||||||||||||
| Red Blood Cell (RBC) Transfusion Burden Categories | RBC units transfused during 56 days prior to the start of treatment. | Count of Participants | Participants |
| |||||||||||||||
| Number of Previous Erythropoiesis-Stimulating Agents (ESA) Therapies for Myelodysplastic Syndromes | Myelodysplastic Syndromes (MDS) | Count of Participants | Participants |
| |||||||||||||||
| Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS) | Erythropoiesis-Stimulating Agents (ESA) | Count of Participants | Participants |
| |||||||||||||||
| International Prognostic Scoring System (IPSS) Risk Category | The International Prognostic Scoring System for MDS (IPSS) 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 | Count of Participants | Participants |
| |||||||||||||||
| Erythropoietin Level | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate) | 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. | 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. | Posted | Number | percentage of participants | Day 2 to Day 142 |
|
|
| |||||||||||||||||||||||||||||||||
| Secondary | Time to Erythroid Hematological Improvement (HI-E) Response | 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. | Efficacy Evaluable Population of participants who responded | Posted | Median | Full Range | days | Day 1 to Day 87 |
| ||||||||||||||||||||||||||||||||||
| Secondary | Duration of Erythroid Hematological Improvement (HI-E) | 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. | Efficacy Evaluable Population of participants who responded | Posted | Median | Full Range | days | Day 1 to 183.7 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression | 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. | Efficacy Evaluable Population of participants who progressed to AML | Posted | Number | weeks | Day 1 to 183.7 weeks |
| |||||||||||||||||||||||||||||||||||
| Secondary | Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression | 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. | Efficacy Evaluable Population of participants who progressed to high risk MDS categories | Posted | Number | weeks | Day 1 to 257.3 weeks |
| |||||||||||||||||||||||||||||||||||
| Secondary | Kaplan-Meier Estimates for Progression-free Survival | 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 | Efficacy Evaluable Population | Posted | Median | 95% Confidence Interval | weeks | Day 1 to 257.3 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Kaplan-Meier Estimates for Overall Survival (OS) | 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. | Efficacy Evaluable Population | Posted | Median | 95% Confidence Interval | weeks | Day 1 to 257.3 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints | Maximum observed serum concentration, obtained directly from the observed concentration versus time data. | Pharmacokinetic (PK) population includes participants with a sufficient amount of post-dose quantifiable PK sotatercept profile. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Cycle 1 Day 8 and !5 up to Cycle 2 Day 1 |
| ||||||||||||||||||||||||||||||||||
| Secondary | Participants With Treatment-Emergent Adverse Events (TEAE) | 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. | Safety population: all participants who receive at least one dose of study medication. | Posted | Count of Participants | Participants | Day 1 up to 59.2 months |
| |||||||||||||||||||||||||||||||||||
| Secondary | Dose Limiting Toxicities (DLTs) | 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 | Safety population | Posted | Count of Participants | Participants | Day 1 to 59.2 months |
| |||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval | 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 | Efficacy Evaluable Population | Posted | Count of Participants | Participants | Day 2 to Day 142 |
|
Day 1 up to 60.7 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sotatercept 0.1 mg/kg | 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. | 1 | 7 | 1 | 7 | 6 | 7 |
| EG001 | Sotatercept 0.3 mg/kg | 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. | 1 | 6 | 2 | 6 | 4 | 6 |
| EG002 | Sotatercept 0.5 mg/kg | 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. | 6 | 21 | 6 | 21 | 18 | 21 |
| EG003 | Sotatercept 1.0 mg/kg | 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). | 6 | 35 | 10 | 35 | 32 | 35 |
| EG004 | Sotatercept 2.0 mg/kg | 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. | 1 | 5 | 2 | 5 | 5 | 5 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Mass | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Escherichia pyelonephritis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Peritoneal abscess | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Diabetic foot | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Aortic stenosis | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Haemolytic anaemia | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Eye haemorrhage | Eye disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Eye inflammation | Eye disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Eyelid oedema | Eye disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Salivary gland enlargement | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Vessel puncture site swelling | General disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Anaphylactic reaction | Immune system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 21.0 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Muscle strain | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 21.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA 21.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Iron overload | Metabolism and nutrition disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.0 | Systematic Assessment |
| |
| Ataxia | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Gynaecomastia | Reproductive system and breast disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Upper-airway cough syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 21.0 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme LLC | 800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 1, 2018 | Apr 30, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000740 | Anemia |
| D009190 | Myelodysplastic Syndromes |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| ID | Term |
|---|---|
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C542017 | ACE-011 |
Not provided
Not provided
Not provided
| >=65 - <75 years |
|
| >=75 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| France |
|
| >200 to <=500 mIU/mL |
|
| >500 mIU/mL |
|
| Missing |
|
| >= 4 units (High Transfusion Burden) |
|
| 1 ESA therapy |
|
| 2 ESA therapies |
|
| 3 ESA therapies |
|
| 1 non-ESA agent |
|
| 2 non-ESA agents |
|
| 3 non-ESA agents |
|
| 4 non-ESA agents |
|
| 5 non-ESA agents |
|
| >5 non-ESA agents |
|
| Intermediate- 1: 0.5 to 1 |
|
| Intermediate- 2: 1.5 to 2 |
|
| High: >= 2.5 |
|
| >200 to <=500 mIU/mL |
|
| >500 mIU/mL |
|
| Missing |
|
|
| NTDE subpopulation |
|
|
| TDE subpopulation |
|
|
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
| OG002 |
| Sotatercept 0.5 mg/kg |
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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
| OG001 |
| Sotatercept 0.3 mg/kg |
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. |
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
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. |
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
| Sotatercept 0.3 mg/kg |
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. |
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
| OG002 | Sotatercept 0.5 mg/kg | 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. |
| OG003 | Sotatercept 1.0 mg/kg | 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). |
| OG004 | Sotatercept 2.0 mg/kg | 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. |
|
|
|
|
|
|
|
|
|
|