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

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

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: Sotatercept

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Weinberg Cancer Institution at Franklin Square
    • Baltimore, Maryland, United States, 21229
      • Saint Agnes Healthcare
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Pennsylvania Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Cappellini MD, Porter J, Origa R, Forni GL, Voskaridou E, Galacteros F, Taher AT, Arlet JB, Ribeil JA, Garbowski M, Graziadei G, Brouzes C, Semeraro M, Laadem A, Miteva D, Zou J, Sung V, Zinger T, Attie KM, Hermine O. Sotatercept, a novel transforming growth factor beta ligand trap, improves anemia in beta-thalassemia: a phase II, open-label, dose-finding study. Haematologica. 2019 Mar;104(3):477-484. doi: 10.3324/haematol.2018.198887. Epub 2018 Oct 18.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2010
• Primary Completion (Actual): September 18, 2012
• Study Completion (Actual): October 29, 2012

Study Registration Dates

• First Submitted: July 21, 2010
• First Submitted That Met QC Criteria: August 26, 2010
• First Posted (Estimated): August 27, 2010

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Solid Tumors; Red Blood Cell Mass; Plasma Volume
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 7962-016; ACE-011-ST-001 (Other Identifier: Celgene)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf