Solid Tumors
Conditions
Keywords
Red Blood Cell Mass, Plasma Volume, Solid Tumors
Brief summary
What hematopoietic precursor compartments as well as hemoglobin subtypes are affected by dosing with sotatercept (ACE-011)? Based upon a similar prior study with Procrit, Celgene has determined that all of these goals could be obtained by an intense 10-patient sotatercept (ACE-011) pharmacodynamic study, completed by two well-known experts in the red cell production field.
Interventions
DRUGSotatercept
single 35 mg SC dose of sotatercept on study Day 1, Day 43, and Day 85
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women ≥18 years of age. * Histologically confirmed diagnosis of a solid tumor malignancy documented by cytology or biopsy. * Presence of metastatic disease. * Hemoglobin value between ≥8.0 to \<11.0 g/dL (≥80 to \<110 g/L). * ≥28 days must have elapsed (prior to pre-dose red blood cell mass / plasma volume test) since previous treatment with erythropoiesis-stimulating agent (including concurrent treatment with intravenous \[IV\] iron). * ≥28 days must have elapsed (prior to Day 1) since the last red blood cell transfusion and receipt of ≤2 units of blood in the past 56 days (prior to Day 1). * Eastern Cooperative Oncology Group (ECOG) Performance status of 0 - 1.
Exclusion criteria
At the time of screening, participants who have any grade ≥3 toxicity (according to the currently active minor version of NCI CTCAE v4.0) except for the following disease-related toxicities: * Hematological events - anemia, thrombocytopenia, neutropenia * Non-hematological events - nausea, vomiting, fatigue, muscle or bone/joint pain
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Red Blood Cell Mass Following a Single Dose of Sotatercept | Baseline (Day 1, pre-dose) and one timepoint between Day 14 and Day 28 | Blood samples were to be collected at baseline (Day 1, pre-dose) and at one timepoint between Day 14 and Day 28, and isotope dilution techniques used, to measure the change from baseline in red blood cell mass following a single dose of sotatercept. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Absolute Reticulocyte Count | Baseline (Day 1, pre-dose) and Day 211 | Blood samples were to be collected at baseline (Day 1, pre-dose) and at Day 211 to measure the change from baseline in absolute reticulocyte count. |
| Change From Baseline in Erythropoietin Levels | Baseline (Day 1, pre-dose) and Day 211 | Blood samples were collected at baseline (Day 1, pre-dose) and at Day 211 to measure the change from baseline in erythropoietin levels. |
| Change From Baseline in Hemoglobin Subtype A Following a Single Dose of Sotatercept | Baseline (Day 1, pre-dose) and Day 29 | Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype A following a single dose of sotatercept. |
| Change From Baseline in Plasma Volume Following a Single Dose of Sotatercept | Baseline (Day 1, pre-dose) and one timepoint between Day 14 and Day 28 | Blood samples were collected at baseline (Day 1, pre-dose) and at one timepoint between Day 14 and Day 28, and isotope dilution techniques used, to measure the change from baseline in plasma volume following a single dose of sotatercept. |
| Change From Baseline in Hemoglobin Subtype C Following a Single Dose of Sotatercept | Baseline (Day 1, pre-dose) and Day 29 | Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype C following a single dose of sotatercept. |
| Number of Participants Who Experienced One or More Adverse Events (AEs) | Up to approximately 7 months | An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. |
| Change From Baseline in Hemoglobin Subtype A2 Following a Single Dose of Sotatercept | Baseline (Day 1, pre-dose) and Day 29 | Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype A2 following a single dose of sotatercept. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sotatercept Participants received a single 35 mg dose of sotatercept by subcutaneous (SC) injection on Day 1, Day 43, and Day 85. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Disease progression | 1 |
Baseline characteristics
| Characteristic | Sotatercept |
|---|---|
| Age, Continuous | 63.8 Years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 5 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 |
Outcome results
Primary
Change From Baseline in Red Blood Cell Mass Following a Single Dose of Sotatercept
Blood samples were to be collected at baseline (Day 1, pre-dose) and at one timepoint between Day 14 and Day 28, and isotope dilution techniques used, to measure the change from baseline in red blood cell mass following a single dose of sotatercept.
Time frame: Baseline (Day 1, pre-dose) and one timepoint between Day 14 and Day 28
Population: No data were collected for Change from Baseline in Red Blood Cell Mass Following a Single Dose of Sotatercept.
Secondary
Change From Baseline in Absolute Reticulocyte Count
Blood samples were to be collected at baseline (Day 1, pre-dose) and at Day 211 to measure the change from baseline in absolute reticulocyte count.
Time frame: Baseline (Day 1, pre-dose) and Day 211
Population: No data were collected for Change from Baseline in Absolute Reticulocyte Count.
Secondary
Change From Baseline in Erythropoietin Levels
Blood samples were collected at baseline (Day 1, pre-dose) and at Day 211 to measure the change from baseline in erythropoietin levels.
Time frame: Baseline (Day 1, pre-dose) and Day 211
Population: All participants who received at least one dose of study treatment and had data for Change from Baseline in Erythropoietin Levels
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sotatercept | Change From Baseline in Erythropoietin Levels | 11.30 IU/L |
Secondary
Change From Baseline in Hemoglobin Subtype A2 Following a Single Dose of Sotatercept
Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype A2 following a single dose of sotatercept.
Time frame: Baseline (Day 1, pre-dose) and Day 29
Population: All participants who received at least one dose of study treatment and had data for Change from Baseline in Hemoglobin Subtype A2 Following a Single Dose of Sotatercept
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sotatercept | Change From Baseline in Hemoglobin Subtype A2 Following a Single Dose of Sotatercept | 0.0 Percentage of hemoglobin subtype A2 |
Secondary
Change From Baseline in Hemoglobin Subtype A Following a Single Dose of Sotatercept
Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype A following a single dose of sotatercept.
Time frame: Baseline (Day 1, pre-dose) and Day 29
Population: All participants who received at least one dose of study treatment and had data for Change from Baseline in Hemoglobin Subtype A Following a Single Dose of Sotatercept
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sotatercept | Change From Baseline in Hemoglobin Subtype A Following a Single Dose of Sotatercept | 0.0 Percentage of hemoglobin subtype A |
Secondary
Change From Baseline in Hemoglobin Subtype C Following a Single Dose of Sotatercept
Blood samples were collected at baseline (Day 1, pre-dose) and on Day 29, and hemoglobin electrophoresis used, to measure the change from baseline in hemoglobin subtype C following a single dose of sotatercept.
Time frame: Baseline (Day 1, pre-dose) and Day 29
Population: All participants who received at least one dose of study treatment and had data for Change from Baseline in Hemoglobin Subtype C Following a Single Dose of Sotatercept
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sotatercept | Change From Baseline in Hemoglobin Subtype C Following a Single Dose of Sotatercept | 0.0 Percentage of hemoglobin subtype C |
Secondary
Change From Baseline in Plasma Volume Following a Single Dose of Sotatercept
Blood samples were collected at baseline (Day 1, pre-dose) and at one timepoint between Day 14 and Day 28, and isotope dilution techniques used, to measure the change from baseline in plasma volume following a single dose of sotatercept.
Time frame: Baseline (Day 1, pre-dose) and one timepoint between Day 14 and Day 28
Population: All participants who received at least one dose of study treatment and had data for Change from Baseline in Plasma Volume Following a Single Dose of Sotatercept
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sotatercept | Change From Baseline in Plasma Volume Following a Single Dose of Sotatercept | -239.50 mL | Standard Deviation 219.91 |
Secondary
Number of Participants Who Experienced One or More Adverse Events (AEs)
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Time frame: Up to approximately 7 months
Population: All participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sotatercept | Number of Participants Who Experienced One or More Adverse Events (AEs) | 4 Participants |