Study to Evaluate Effect of a Single Dose of Sotatercept (ACE-011) on Red Blood Cell Mass and Plasma Volume in Participants With Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2, Open-Label, Pharmacodynamic Study to Evaluate the Effect of Sotatercept (ACE-011) on Red Blood Cell Mass and Plasma Volume in Subjects With Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Sotatercept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sotatercept<br>Participants will receive a single 35 mg dose of sotatercept by subcutaneous (SC) injection on Day 1, Day 43, and Day 85. | Drug: Sotatercept<br>* single 35 mg SC dose of sotatercept on study Day 1, Day 43, and Day 85<br>* Other names: ACE 011;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Day 1, pre-dose) and one timepoint between Day 14 and Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Day 1, pre-dose) and one timepoint between Day 14 and Day 28 | 
| 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. | Baseline (Day 1, pre-dose) and Day 211 | 
| 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. | Baseline (Day 1, pre-dose) and Day 211 | 
| 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. | Baseline (Day 1, pre-dose) and Day 29 | 
| 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. | Baseline (Day 1, pre-dose) and Day 29 | 
| 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. | Baseline (Day 1, pre-dose) and Day 29 | 
| 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. | Up to approximately 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Red Blood Cell Mass, Plasma Volume, Solid Tumors