Trial Outcomes & Findings for Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML) (NCT NCT01736683)
NCT ID: NCT01736683
Last Updated: 2022-10-24
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
74 participants
Primary outcome timeframe
Day 2 to Day 142
Results posted on
2022-10-24
Participant Flow
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.
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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).
|
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.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
6
|
21
|
35
|
5
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
7
|
6
|
21
|
35
|
5
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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).
|
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.
|
|---|---|---|---|---|---|
|
Overall Study
Disease Relapse
|
0
|
0
|
2
|
1
|
0
|
|
Overall Study
Adverse Event
|
0
|
2
|
2
|
3
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
3
|
1
|
1
|
|
Overall Study
Lack of Therapeutic Effect
|
7
|
4
|
13
|
20
|
1
|
|
Overall Study
Progressive Disease
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Other
|
0
|
0
|
1
|
9
|
1
|
Baseline Characteristics
Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML)
Baseline characteristics by cohort
| Measure |
Sotatercept 0.1 mg/kg
n=7 Participants
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
n=6 Participants
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
n=21 Participants
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
n=35 Participants
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
n=5 Participants
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
n=74 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
67 years
STANDARD_DEVIATION 8.3 • n=93 Participants
|
75 years
STANDARD_DEVIATION 6.9 • n=4 Participants
|
69 years
STANDARD_DEVIATION 8.0 • n=27 Participants
|
71 years
STANDARD_DEVIATION 8.2 • n=483 Participants
|
69 years
STANDARD_DEVIATION 13.0 • n=36 Participants
|
70 years
STANDARD_DEVIATION 8.4 • n=10 Participants
|
|
Age, Customized
<65 years
|
3 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
17 Participants
n=10 Participants
|
|
Age, Customized
>=65 - <75 years
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
17 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
32 Participants
n=10 Participants
|
|
Age, Customized
>=75 years
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
12 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
25 Participants
n=10 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
17 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
28 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
17 Participants
n=27 Participants
|
18 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
46 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
13 Participants
n=27 Participants
|
19 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
49 Participants
n=10 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
23 Participants
n=10 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
1 Participants
n=10 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
18 Participants
n=483 Participants
|
3 Participants
n=36 Participants
|
48 Participants
n=10 Participants
|
|
Race (NIH/OMB)
More than one race
|
NA Participants
n=93 Participants
|
NA Participants
n=4 Participants
|
NA Participants
n=27 Participants
|
NA Participants
n=483 Participants
|
NA Participants
n=36 Participants
|
NA Participants
n=10 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
24 Participants
n=10 Participants
|
|
Region of Enrollment
United States
|
7 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
18 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
50 Participants
n=10 Participants
|
|
Region of Enrollment
France
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
17 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
24 Participants
n=10 Participants
|
|
Height
|
1.70 meters
STANDARD_DEVIATION 0.110 • n=93 Participants
|
1.75 meters
STANDARD_DEVIATION 0.054 • n=4 Participants
|
1.70 meters
STANDARD_DEVIATION 0.093 • n=27 Participants
|
1.68 meters
STANDARD_DEVIATION 0.089 • n=483 Participants
|
1.56 meters
STANDARD_DEVIATION 0.043 • n=36 Participants
|
1.68 meters
STANDARD_DEVIATION 0.095 • n=10 Participants
|
|
Weight
|
85.3 kg
STANDARD_DEVIATION 21.79 • n=93 Participants
|
79.5 kg
STANDARD_DEVIATION 13.90 • n=4 Participants
|
77.9 kg
STANDARD_DEVIATION 13.97 • n=27 Participants
|
73.5 kg
STANDARD_DEVIATION 15.55 • n=483 Participants
|
56.4 kg
STANDARD_DEVIATION 7.25 • n=36 Participants
|
75.2 kg
STANDARD_DEVIATION 16.14 • n=10 Participants
|
|
Erythropoietin level
<=200 mIU/mL
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
29 Participants
n=10 Participants
|
|
Erythropoietin level
>200 to <=500 mIU/mL
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
15 Participants
n=10 Participants
|
|
Erythropoietin level
>500 mIU/mL
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
25 Participants
n=10 Participants
|
|
Erythropoietin level
Missing
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
5 Participants
n=10 Participants
|
|
Red Blood Cell (RBC) Transfusion Burden Categories
< 4 units (Low Transfusion Burden)
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
8 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
12 Participants
n=10 Participants
|
|
Red Blood Cell (RBC) Transfusion Burden Categories
>= 4 units (High Transfusion Burden)
|
7 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
27 Participants
n=483 Participants
|
4 Participants
n=36 Participants
|
62 Participants
n=10 Participants
|
|
Number of Previous Erythropoiesis-Stimulating Agents (ESA) Therapies for Myelodysplastic Syndromes
0 ESA therapies
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
|
Number of Previous Erythropoiesis-Stimulating Agents (ESA) Therapies for Myelodysplastic Syndromes
1 ESA therapy
|
6 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
23 Participants
n=483 Participants
|
3 Participants
n=36 Participants
|
45 Participants
n=10 Participants
|
|
Number of Previous Erythropoiesis-Stimulating Agents (ESA) Therapies for Myelodysplastic Syndromes
2 ESA therapies
|
0 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
10 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
24 Participants
n=10 Participants
|
|
Number of Previous Erythropoiesis-Stimulating Agents (ESA) Therapies for Myelodysplastic Syndromes
3 ESA therapies
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
3 Participants
n=10 Participants
|
|
Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS)
0 non-ESA agents
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
11 Participants
n=10 Participants
|
|
Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS)
1 non-ESA agent
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
25 Participants
n=10 Participants
|
|
Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS)
2 non-ESA agents
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
17 Participants
n=10 Participants
|
|
Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS)
3 non-ESA agents
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
2 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
8 Participants
n=10 Participants
|
|
Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS)
4 non-ESA agents
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
3 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
6 Participants
n=10 Participants
|
|
Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS)
5 non-ESA agents
|
1 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
2 Participants
n=10 Participants
|
|
Number of Previous Non-ESA Agents for Myelodysplastic Syndromes (MDS)
>5 non-ESA agents
|
1 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
5 Participants
n=10 Participants
|
|
International Prognostic Scoring System (IPSS) Risk Category
Low - 0
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
11 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
24 Participants
n=10 Participants
|
|
International Prognostic Scoring System (IPSS) Risk Category
Intermediate- 1: 0.5 to 1
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
16 Participants
n=27 Participants
|
24 Participants
n=483 Participants
|
5 Participants
n=36 Participants
|
50 Participants
n=10 Participants
|
|
International Prognostic Scoring System (IPSS) Risk Category
Intermediate- 2: 1.5 to 2
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
International Prognostic Scoring System (IPSS) Risk Category
High: >= 2.5
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
0 Participants
n=10 Participants
|
|
Erythropoietin Level
<=200 mIU/mL
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
29 Participants
n=10 Participants
|
|
Erythropoietin Level
>200 to <=500 mIU/mL
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
6 Participants
n=483 Participants
|
0 Participants
n=36 Participants
|
15 Participants
n=10 Participants
|
|
Erythropoietin Level
>500 mIU/mL
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
9 Participants
n=27 Participants
|
9 Participants
n=483 Participants
|
2 Participants
n=36 Participants
|
25 Participants
n=10 Participants
|
|
Erythropoietin Level
Missing
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
4 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
5 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Day 2 to Day 142Population: 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.
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.
Outcome measures
| Measure |
Sotatercept 0.1 mg/kg
n=7 Participants
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
n=6 Participants
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
n=21 Participants
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
n=35 Participants
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
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)
All participants
|
0 percentage of participants
|
66.7 percentage of participants
|
42.9 percentage of participants
|
60.0 percentage of participants
|
40.0 percentage of participants
|
|
Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)
NTDE subpopulation
|
—
|
—
|
33.3 percentage of participants
|
62.5 percentage of participants
|
100 percentage of participants
|
|
Percentage of Participants With Erythroid Hematological Improvement (HI-E) Starting Before the Completion of Five Cycles of Treatment (Responder Rate)
TDE subpopulation
|
0 percentage of participants
|
66.7 percentage of participants
|
44.4 percentage of participants
|
59.3 percentage of participants
|
25.0 percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 to Day 87Population: Efficacy Evaluable Population of participants who responded
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.
Outcome measures
| Measure |
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.
|
Sotatercept 0.3 mg/kg
n=4 Participants
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
n=9 Participants
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
n=21 Participants
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
n=2 Participants
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.
|
|---|---|---|---|---|---|
|
Time to Erythroid Hematological Improvement (HI-E) Response
TDE subpopulation
|
—
|
24.0 days
Interval 2.0 to 44.0
|
1.5 days
Interval 1.0 to 2.0
|
1.5 days
Interval 1.0 to 86.0
|
87 days
Interval 87.0 to 87.0
|
|
Time to Erythroid Hematological Improvement (HI-E) Response
All participants
|
—
|
24.0 days
Interval 2.0 to 44.0
|
1.0 days
Interval 1.0 to 2.0
|
1.0 days
Interval 1.0 to 86.0
|
48 days
Interval 9.0 to 87.0
|
|
Time to Erythroid Hematological Improvement (HI-E) Response
NTDE subpopulation
|
—
|
—
|
1.0 days
Interval 1.0 to 1.0
|
1.0 days
Interval 1.0 to 52.0
|
9.0 days
Interval 9.0 to 9.0
|
SECONDARY outcome
Timeframe: Day 1 to 183.7 weeksPopulation: Efficacy Evaluable Population of participants who responded
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.
Outcome measures
| Measure |
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.
|
Sotatercept 0.3 mg/kg
n=4 Participants
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
n=9 Participants
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
n=21 Participants
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
n=2 Participants
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.
|
|---|---|---|---|---|---|
|
Duration of Erythroid Hematological Improvement (HI-E)
All participants
|
—
|
62.5 days
Interval 62.0 to 69.0
|
104.0 days
Interval 56.0 to 1794.0
|
133.0 days
Interval 58.0 to 1554.0
|
96.0 days
Interval 58.0 to 134.0
|
|
Duration of Erythroid Hematological Improvement (HI-E)
TDE subpopulation
|
—
|
62.5 days
Interval 62.0 to 69.0
|
105.5 days
Interval 56.0 to 1794.0
|
96.5 days
Interval 58.0 to 1033.0
|
58.0 days
Interval 58.0 to 58.0
|
|
Duration of Erythroid Hematological Improvement (HI-E)
NTDE subpopulation
|
—
|
—
|
79.0 days
Interval 79.0 to 79.0
|
1043.0 days
Interval 69.0 to 1554.0
|
134.0 days
Interval 134.0 to 134.0
|
SECONDARY outcome
Timeframe: Day 1 to 183.7 weeksPopulation: Efficacy Evaluable Population of participants who progressed to AML
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.
Outcome measures
| Measure |
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.
|
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.
|
Sotatercept 0.5 mg/kg
n=1 Participants
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
n=1 Participants
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
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.
|
|---|---|---|---|---|---|
|
Time to Progression to Acute Myeloid Leukemia (AML) for Participants Who Had Progression
|
—
|
—
|
45.6 weeks
|
78.0 weeks
|
—
|
SECONDARY outcome
Timeframe: Day 1 to 257.3 weeksPopulation: Efficacy Evaluable Population of participants who progressed to high risk MDS categories
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.
Outcome measures
| Measure |
Sotatercept 0.1 mg/kg
n=1 Participants
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
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
n=1 Participants
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
n=1 Participants
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
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.
|
|---|---|---|---|---|---|
|
Time to Progression to Events of Higher Risk Myelodysplastic Syndromes (MDS) Using the International Prognostic Scoring System (IPSS) For Participants Who Had Progression
|
15.1 weeks
|
—
|
24.7 weeks
|
67.4 weeks
|
—
|
SECONDARY outcome
Timeframe: Day 1 to 257.3 weeksPopulation: Efficacy Evaluable Population
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
Outcome measures
| Measure |
Sotatercept 0.1 mg/kg
n=7 Participants
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
n=6 Participants
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
n=21 Participants
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
n=35 Participants
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
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Kaplan-Meier Estimates for Progression-free Survival
|
82.7 weeks
Interval 15.1 to 82.7
|
NA weeks
Interval 91.1 to
not enough events to allow for calculation
|
NA weeks
Interval 58.6 to
not enough events to allow for calculation
|
NA weeks
not enough events to allow for calculation
|
NA weeks
Interval 79.9 to
not enough events to allow for calculation
|
SECONDARY outcome
Timeframe: Day 1 to 257.3 weeksPopulation: Efficacy Evaluable Population
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.
Outcome measures
| Measure |
Sotatercept 0.1 mg/kg
n=7 Participants
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
n=6 Participants
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
n=21 Participants
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
n=35 Participants
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
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Kaplan-Meier Estimates for Overall Survival (OS)
|
82.7 weeks
not enough events to allow for calculation
|
NA weeks
Interval 91.0 to
not enough events to allow for calculation
|
NA weeks
Interval 58.6 to
not enough events to allow for calculation
|
NA weeks
not enough events to allow for calculation
|
NA weeks
Interval 79.1 to
not enough events to allow for calculation
|
SECONDARY outcome
Timeframe: Cycle 1 Day 8 and !5 up to Cycle 2 Day 1Population: Pharmacokinetic (PK) population includes participants with a sufficient amount of post-dose quantifiable PK sotatercept profile.
Maximum observed serum concentration, obtained directly from the observed concentration versus time data.
Outcome measures
| Measure |
Sotatercept 0.1 mg/kg
n=7 Participants
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
n=6 Participants
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
n=21 Participants
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
n=35 Participants
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
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints
Cycle 1 Day 15
|
240.31 ng/mL
Geometric Coefficient of Variation 75.32
|
1207.68 ng/mL
Geometric Coefficient of Variation 16.14
|
1869.52 ng/mL
Geometric Coefficient of Variation 36.97
|
5149.74 ng/mL
Geometric Coefficient of Variation 36.04
|
8303.73 ng/mL
Geometric Coefficient of Variation 43.57
|
|
Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints
Cycle 1 Day 8
|
288.06 ng/mL
Geometric Coefficient of Variation 70.94
|
1426.00 ng/mL
Geometric Coefficient of Variation 27.76
|
2237.46 ng/mL
Geometric Coefficient of Variation 40.77
|
6525.37 ng/mL
Geometric Coefficient of Variation 28.31
|
12886.14 ng/mL
Geometric Coefficient of Variation 30.47
|
|
Pharmacokinetic Parameters of Sotatercept: Serum Concentration at Various Study Timepoints
Cycle 2 Day 1
|
252.20 ng/mL
Geometric Coefficient of Variation 28.43
|
957.58 ng/mL
Geometric Coefficient of Variation 18.63
|
1323.91 ng/mL
Geometric Coefficient of Variation 44.40
|
3467.58 ng/mL
Geometric Coefficient of Variation 57.06
|
5329.63 ng/mL
Geometric Coefficient of Variation 38.27
|
SECONDARY outcome
Timeframe: Day 1 up to 59.2 monthsPopulation: Safety population: all participants who receive at least one dose of study medication.
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.
Outcome measures
| Measure |
Sotatercept 0.1 mg/kg
n=7 Participants
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
n=6 Participants
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
n=21 Participants
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
n=35 Participants
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
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>= 1 Treatment-emergent adverse event (TEAE)
|
6 Participants
|
4 Participants
|
20 Participants
|
34 Participants
|
5 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 Serious TEAE related to treatment
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 Treatment-related TEAE
|
2 Participants
|
3 Participants
|
7 Participants
|
18 Participants
|
4 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 Serious TEAE
|
1 Participants
|
2 Participants
|
6 Participants
|
10 Participants
|
2 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 TEAE severity 3 or 4
|
1 Participants
|
2 Participants
|
9 Participants
|
13 Participants
|
2 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 TEAE severity grade 3/4 related to treatment
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 TEAE leading to death
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 TEAE leading to dose reduction
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 TEAE leading to dose interruption
|
0 Participants
|
1 Participants
|
2 Participants
|
9 Participants
|
1 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>=1 TEAE leading to dose interruption + reduction
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Participants With Treatment-Emergent Adverse Events (TEAE)
>= 1 TEAE leading to drug discontinuation
|
0 Participants
|
2 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Day 1 to 59.2 monthsPopulation: Safety population
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
Outcome measures
| Measure |
Sotatercept 0.1 mg/kg
n=7 Participants
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
n=6 Participants
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
n=21 Participants
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
n=35 Participants
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
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Dose Limiting Toxicities (DLTs)
3. =140 systolic and increase > 20 mmHg base
|
0 Participants
|
1 Participants
|
5 Participants
|
10 Participants
|
2 Participants
|
|
Dose Limiting Toxicities (DLTs)
1. Increase to >= 140 mmHg systolic
|
1 Participants
|
1 Participants
|
8 Participants
|
19 Participants
|
2 Participants
|
|
Dose Limiting Toxicities (DLTs)
2. Increase to >=90 mmHg diastolic
|
0 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Dose Limiting Toxicities (DLTs)
4. >=90 mmHg diastolic and increase > 20 mmHg base
|
0 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
|
Dose Limiting Toxicities (DLTs)
5. Introduction of new anti-hypertension med
|
0 Participants
|
0 Participants
|
4 Participants
|
3 Participants
|
1 Participants
|
|
Dose Limiting Toxicities (DLTs)
6. Incre in dose of baseline anti-hypertension med
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Dose Limiting Toxicities (DLTs)
7.>= Grade 2 hypertension TEAE
|
0 Participants
|
1 Participants
|
2 Participants
|
4 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 2 to Day 142Population: Efficacy Evaluable Population
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
Outcome measures
| Measure |
Sotatercept 0.1 mg/kg
n=7 Participants
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
n=6 Participants
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
n=21 Participants
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
n=35 Participants
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
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval
All participants
|
0 Participants
|
1 Participants
|
3 Participants
|
15 Participants
|
1 Participants
|
|
Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval
NTDE subpopulation
|
—
|
—
|
1 Participants
|
6 Participants
|
1 Participants
|
|
Number of Participants Who Achieved Red Blood Cell (RBC)-Transfusion Independence During the Erythroid Hematological Improvement (HI-E) Interval
TDE subpopulation
|
0 Participants
|
1 Participants
|
2 Participants
|
9 Participants
|
0 Participants
|
Adverse Events
Sotatercept 0.1 mg/kg
Serious events: 1 serious events
Other events: 6 other events
Deaths: 1 deaths
Sotatercept 0.3 mg/kg
Serious events: 2 serious events
Other events: 4 other events
Deaths: 1 deaths
Sotatercept 0.5 mg/kg
Serious events: 6 serious events
Other events: 18 other events
Deaths: 6 deaths
Sotatercept 1.0 mg/kg
Serious events: 10 serious events
Other events: 32 other events
Deaths: 6 deaths
Sotatercept 2.0 mg/kg
Serious events: 2 serious events
Other events: 5 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Sotatercept 0.1 mg/kg
n=7 participants at risk
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
n=6 participants at risk
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
n=21 participants at risk
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
n=35 participants at risk
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
n=5 participants at risk
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.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Mass
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Pyrexia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Bronchitis
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Escherichia pyelonephritis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Influenza
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Lung infection
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Peritoneal abscess
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Investigations
Blood pressure increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Investigations
International normalised ratio increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Psychiatric disorders
Delirium
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Skin and subcutaneous tissue disorders
Diabetic foot
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Vascular disorders
Aortic stenosis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Vascular disorders
Hypotension
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
Other adverse events
| Measure |
Sotatercept 0.1 mg/kg
n=7 participants at risk
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
n=6 participants at risk
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
n=21 participants at risk
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
n=35 participants at risk
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
n=5 participants at risk
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.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Eye disorders
Eye haemorrhage
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Eye disorders
Eye inflammation
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Eye disorders
Vitreous floaters
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
14.3%
5/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
28.6%
6/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/7 • Day 1 up to 60.7 months
|
33.3%
2/6 • Day 1 up to 60.7 months
|
33.3%
7/21 • Day 1 up to 60.7 months
|
25.7%
9/35 • Day 1 up to 60.7 months
|
40.0%
2/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
19.0%
4/21 • Day 1 up to 60.7 months
|
22.9%
8/35 • Day 1 up to 60.7 months
|
40.0%
2/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Salivary gland enlargement
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Stomatitis
|
14.3%
1/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Toothache
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
14.3%
3/21 • Day 1 up to 60.7 months
|
25.7%
9/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
General disorders
Asthenia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
14.3%
3/21 • Day 1 up to 60.7 months
|
20.0%
7/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Chest discomfort
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Face oedema
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Fatigue
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
28.6%
6/21 • Day 1 up to 60.7 months
|
31.4%
11/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
General disorders
Gait disturbance
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Influenza like illness
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Injection site reaction
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Oedema
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
General disorders
Oedema peripheral
|
28.6%
2/7 • Day 1 up to 60.7 months
|
33.3%
2/6 • Day 1 up to 60.7 months
|
28.6%
6/21 • Day 1 up to 60.7 months
|
31.4%
11/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
General disorders
Peripheral swelling
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
General disorders
Pyrexia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
19.0%
4/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
General disorders
Vessel puncture site swelling
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Bronchitis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Laryngitis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Tooth infection
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
14.3%
5/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Infections and infestations
Urinary tract infection
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
40.0%
2/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/7 • Day 1 up to 60.7 months
|
33.3%
2/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
14.3%
3/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
19.0%
4/21 • Day 1 up to 60.7 months
|
14.3%
5/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Investigations
Blood creatinine increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Investigations
Creatinine renal clearance decreased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Investigations
Lipase increased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Investigations
Platelet count decreased
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
19.0%
4/21 • Day 1 up to 60.7 months
|
22.9%
8/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Metabolism and nutrition disorders
Iron overload
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.3%
1/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Osteopenia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
14.3%
3/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Nervous system disorders
Ataxia
|
14.3%
1/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Nervous system disorders
Dizziness
|
14.3%
1/7 • Day 1 up to 60.7 months
|
33.3%
2/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
17.1%
6/35 • Day 1 up to 60.7 months
|
40.0%
2/5 • Day 1 up to 60.7 months
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Nervous system disorders
Headache
|
42.9%
3/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
19.0%
4/21 • Day 1 up to 60.7 months
|
14.3%
5/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Psychiatric disorders
Depression
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Reproductive system and breast disorders
Gynaecomastia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
1/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
17.1%
6/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
28.6%
6/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
22.9%
8/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
0.00%
0/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.3%
1/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
5.7%
2/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
0.00%
0/21 • Day 1 up to 60.7 months
|
2.9%
1/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
|
Vascular disorders
Hypertension
|
0.00%
0/7 • Day 1 up to 60.7 months
|
16.7%
1/6 • Day 1 up to 60.7 months
|
9.5%
2/21 • Day 1 up to 60.7 months
|
11.4%
4/35 • Day 1 up to 60.7 months
|
20.0%
1/5 • Day 1 up to 60.7 months
|
|
Vascular disorders
Hypotension
|
0.00%
0/7 • Day 1 up to 60.7 months
|
0.00%
0/6 • Day 1 up to 60.7 months
|
4.8%
1/21 • Day 1 up to 60.7 months
|
8.6%
3/35 • Day 1 up to 60.7 months
|
0.00%
0/5 • Day 1 up to 60.7 months
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme LLC
Phone: 800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER