Overview

This trial is active, not recruiting.

Conditions beta thalassemia major, beta thalassemia intermedia
Treatments dose level 1a, dose level 1b, dose level 2, dose level 3, dose level 4, dose level 5
Phase phase 2
Sponsor Celgene Corporation
Start date October 2012
End date May 2015
Trial size 46 participants
Trial identifier NCT01571635, 2011-005659-15, ACE-011-B-THAL-001

Summary

Dose finding study to determine the safety and tolerability of Sotatercept (ACE-011) in adults with Beta (β)-Thalassemia

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Experimental 0.1 mg/kg (dose level 1a) - Starting dose 0.1 mg/kg to 1.5 mg/kg. Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period
dose level 1a
(Experimental)
Experimental 0.3 mg/kg (dose level 1b) - Starting dose 0.1 mg/kg to 1.5 mg/kg. Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period
dose level 1b
(Experimental)
Experimental 0.5 mg/kg (dose level 2) - Escalation dose 0.1 mg/kg to 1.5 mg/kg. Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period
dose level 2
(Experimental)
Experimental 0.75 mg/kg (dose level 3) - Escalation dose 0.1 mg/kg to 1.5 mg/kg. Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period
dose level 3
(Experimental)
Experimental 1.0 mg/kg (dose level 4) - Escalation dose 0.1 mg/kg to 1.5 mg/kg. Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period
dose level 4
(Experimental)
Experimental 1.5 mg/kg (dose level 5) - Escalation dose 0.1 mg/kg to 1.5 mg/kg. Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period
dose level 5

Primary Outcomes

Measure
Potential Recommended Dose (PRD)
time frame: Up to 27 months
Actual Recommended Dose (RD)
time frame: Up to 27 months

Secondary Outcomes

Measure
Reduction of Transfusion Burden
time frame: Up to 27 months
Number of Participants with Adverse Events
time frame: Up to 27 months
PK-Observed Maximum Concentration (Cmax)
time frame: Up to 16 samples over 27 months
PK-Time to Maximum Concentration (Tmax)
time frame: Up to 16 samples over 27 months
PK-Area Under the Concentration-Time Curve (AUC)
time frame: Up to 16 samples over 27 months
PK-Concentration of Anti-Sotatercept Antibody in Serum
time frame: Up to 16 samples over 27 months
Hgb Level Increase
time frame: Up to 27 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Men and women ≥ 18 years of age at the time of signing the informed consent document with a diagnosis of β-thalassemia major (including all subtypes) or β-thalassemia intermedia. 2. For transfusion dependent subjects: permanent transfusion dependency is defined as requiring packed red blood cells (pRBCs) and iron chelation therapy: - Average transfusion requirement of at least 2 units per 30 days of pRBCs (Gale, 2011) confirmed for a minimum of 168 days (six months) immediately preceding enrollment (study Day 1); - No transfusion-free period of more than 45 consecutive days during the 168 days immediately preceding enrollment; - Mean prior transfusion Hgb level is ≤ 10.5 g/dL for 168 days immediately preceding enrollment (study Day 1) and the last pre-transfusion Hgb immediately preceding enrollment (study Day 1) is ≤ 10.5 g/dL. 3. For non-transfusion dependent subjects: non-transfusion dependency is defined as transfusion free, with the exception of ≤ one episode of transfusion in the period of a minimum of 168 days immediately preceding enrollment (One episode of transfusion is defined as ≤ 4 transfusion units administered, occurring within 168 days immediately preceding enrollment due to concurrent illness [e.g. infection], [Guidelines Clin Management of Thalassaemia, 2008]). 4. Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 to 1. 5. No concurrent severe hepatic disease: - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) no greater than 3 x upper limit of normal (ULN); - Albumin ≥ 3 g/dL. 6. Serum creatinine ≤ 1.5 x ULN and creatinine clearance > 60 mL/min. 7. Females of childbearing potential (FCBP) participating in the study are to use highly effective methods of birth control during study participation and for 112 days (approximately five times the mean terminal half-life of sotatercept [23 days] based on multiple-dose PK data) following the last dose of sotatercept. FCBP must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test within 3 days of sotatercept dosing (study Day 1). Subjects must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of sotatercept. A FCBP of childbearing potential is a sexually mature woman who has not undergone a hysterectomy or bilateral oophorectomy or who has not been postmenopausal for at least 24 consecutive months (ie, who has had menses at some time in the preceding 24 months). 8. Males must agree to use a latex condom during any sexual contact with FCBPs while participating in the study and for 112 days following the last dose of sotatercept, even if he has undergone a successful vasectomy. Subjects must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of sotatercept. 9. Agreement to adhere to the study visit schedule, understand and comply with all protocol requirements. 10. Understand and provide written informed consent. Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment: 1. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 2. Evidence of active hepatitis C (HCV) infection, or active infectious hepatitis B, or known positive for human immunodeficiency virus (HIV). 3. Known history of thromboembolic events ≥ Grade 3 according to NCI CTCAE version 4.0 (current active minor version). 4. Subjects with insulin dependent diabetes. 5. Subjects with major cardiac problems such as: - Major risk of heart failure - Cardiac arrhythmia which requires treatment (i.e atrial fibrillation). 6. Treatment with another investigational drug or device < 28 days prior to study entry as well as any prior exposure to sotatercept. 7. Use of an erythropoiesis stimulating agent (ESA) within the 28 days prior to enrollment (study Day 1). 8. Subjects on hydroxyurea treatment for which the dose was changed in the last one year prior to subject enrollment. 9. Subjects on long-term anticoagulant therapy, such as heparin or warfarin. 10. Subjects who started bisphosphonates within the last three months prior to subject enrollment. 11. Pregnant or lactating females. 12. Uncontrolled hypertension. Controlled hypertension for this protocol is considered ≤ Grade 1 according to NCI CTCAE version 4.0 (current active minor version) 13. A history of major organ damage including: - Liver disease with ALT > 3 x ULN or histopathological evidence of liver cirrhosis on liver biopsy; - Heart disease with ejection fraction ≥ Grade 2 according to NCI CTCAE version 4.0 (current active minor version); - Kidney disease with a calculated creatinine clearance < 40 mL/min (Cockcroft-Gault formula); - Pulmonary fibrosis or pulmonary hypertension confirmed by a specialist. 14. Adrenal insufficiency. 15. Heart failure as classified by the New York Heart Association (NYHA) classification of 3 or higher (Appendix C). 16. Major surgery within 30 days prior to study Day 1 (subjects must have completely recovered from any previous surgery prior to study Day 1). 17. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see Investigator Brochure)

Additional Information

Official title A Phase 2A, Open-label Dose Finding Study to Determine the Safety and Tolerability of Sotatercept (ACE-011) in Adults With BETA(b)-THALASSEMIA.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Celgene Corporation.