Study to Determine the Safety and Tolerability of Sotatercept (ACE-011) in Adults With Beta( β)- Thalassemia.

NCT ID: NCT01571635

Last Updated: 2023-06-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-10
• Study Completion Date: 2022-05-24

Brief Summary

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

Conditions

Beta Thalassemia Major; Beta Thalassemia Intermedia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sotatercept dose level 0.1mg/kg

Experimental 0.1 mg/kg -Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period

Group Type: EXPERIMENTAL

SOTATERCEPT (ACE-011)

Intervention Type: DRUG

0.1 mg/kg to 1.5mg/kg Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period.

Sotatercept dose level 0.3mg/ kg

Experimental 0.3 mg/kg - Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period

Group Type: EXPERIMENTAL

SOTATERCEPT (ACE-011)

Intervention Type: DRUG

0.1 mg/kg to 1.5mg/kg Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period.

Sotatercept dose level 0.5mg/kg

Experimental 0.5 mg/kg -Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period

Group Type: EXPERIMENTAL

SOTATERCEPT (ACE-011)

Intervention Type: DRUG

0.1 mg/kg to 1.5mg/kg Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period.

Sotatercept dose level 0.75mg/kg

Experimental 0.75 mg/kg - Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period

Group Type: EXPERIMENTAL

SOTATERCEPT (ACE-011)

Intervention Type: DRUG

0.1 mg/kg to 1.5mg/kg Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period.

Sotatercept dose level 1.0mg/kg

Experimental 1.0 mg/kg -Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period

Group Type: EXPERIMENTAL

SOTATERCEPT (ACE-011)

Intervention Type: DRUG

0.1 mg/kg to 1.5mg/kg Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period.

Sotatercept dose level 1.5mg/kg

Experimental 1.5 mg/kg -Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period

Group Type: EXPERIMENTAL

SOTATERCEPT (ACE-011)

Intervention Type: DRUG

0.1 mg/kg to 1.5mg/kg Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period.

Interventions

SOTATERCEPT (ACE-011)

0.1 mg/kg to 1.5mg/kg Sotatercept will be administered as a subcutaneous injection once every 21 days during the treatment period.

Intervention Type: DRUG

Other Intervention Names

(ACE-011)

Eligibility Criteria

Inclusion Criteria

• 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.
• 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/30 days of pRBCs (Gale, 2011) confirmed for a minimum of 168 days (six months) immediately preceding enrollment (study Day 1, first Dose);
• No transfusion-free period of more than 45 consecutive days during the 168 days immediately preceding enrollment (study Day 1, first Dose);
• Prior transfusion hemoglobin levels ≤ 10.5 g/dL.
• Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 to 1
• No concurrent severe hepatic disease:

• Aspartate Aminotransferase (AST) or Alanine Transaminase (ALT) no greater than 3 x upper limit of normal (ULN);
• Albumin ≥ 3 g/dL.
• Serum creatinine ≤ 1.5 x ULN.
• Females of childbearing potential 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 three days of Sotatercept dosing (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 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 (i.e., who has had menses at some time in the preceding 24 months).
• Males must agree to use a latex condom during any sexual contact with FCBSs 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.
• Agreement to adhere to the study visit schedule, understand and comply with all protocol requirements.
• Understand and provide written informed consent.

Exclusion Criteria

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing participating in the study.
• Evidence of active Hepatitis C antibody (HCV), Hepatitis B surface antigen (HBsAg and HB core Ab), or Human Immunodeficiency Virus (HIV) antibody.
• Known history of thromboembolic events ≥ Grade 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0 (current active minor version).
• Subjects with insulin dependent diabetes.
• Subjects with major cardiac problems such as:

• Major risk of heart failure, confirmed with myocardiac T2* ≤ 10 ms. Myocardiac T2* performed in the last one and a half years prior to subject enrollment (study Day 1, first Dose) will be considered valid.
• Cardiac arrhythmia which requires treatment (i.e. atrial fibrillation).
• Treatment with another investigational drug or device < 28 days prior to study entry.
• Use of an Erythropoiesis Stimulating Agent (ESA) within the 28 days prior to enrollment (study Day 1, first Dose).
• Subjects on hydroxyurea treatment for which the dose was changed in the last one year prior to subject enrollment (study Day 1, first Dose).
• Subjects on anticoagulant therapy, such as warfarin.
• Subjects who started bisphosphonates within the last three months prior to subject enrollment (study Day 1, first Dose).
• Pregnant or lactating females.
• Uncontrolled hypertension. Controlled hypertension for this protocol is considered ≤ Grade 1 according to NCI CTCAE version 4.0 (current active minor version) (Appendix B).
• A history of major organ damage including:

• Liver disease with ALT > 3x 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 as confirmed by a specialist.
• Adrenal insufficiency.
• Heart failure as classified by the New York Heart Association (NYHA) classification of 3 or higher (Appendix C).
• Major surgery within 30 days prior to study Day 1 (subjects must have completely recovered from any previous surgery prior to study Day 1).
• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the Investigational Product (see Investigator Brochure).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Hopital Henri Mondor

Créteil, , France

Groupe Hospitalier Henri Mondor

Créteil, , France

Hospital of Necker

Paris, , France

Local Institution - 001

Paris, , France

Hôpital Necker-Enfants Malades

Paris, , France

Local Institution - 300

Ampelokipi - Athens, , Greece

Laiko General Hospital

Ampelokipi - Athens, , Greece

Universita degli Studi di Cagliari - ASL8

Cagliari, , Italy

Universita Degli Studi Di Cagliari

Cagliari, , Italy

Local Institution - 200

Genoa, , Italy

Ospedale Galliera

Genoa, , Italy

Ente Ospedaliero Ospedali Galliera

Genova, , Italy

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, , Italy

Fondazione IRCCS Ospedale Maggiore

Milan, , Italy

Local Institution - 201

Milan, , Italy

Local Institution - 100

London, , United Kingdom

UCL Cancer Institute

London, , United Kingdom

UCL Cancer Institue

London, , United Kingdom

Countries

France; Greece; Italy; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 30337358 (View on PubMed)

Cappellini M, et al. A Phase 2a, Open-Label, Dose-Finding Study to Determine the Safety and Tolerability of Sotatercept (ACE-011) in Adults With Beta ( )-Thalassemia: Interim Results. Presented at the 55th Annual Meeting of the American Society of Hematology (ASH), December 7-10, 2013, New Orleans, LA. Abstract No. 3448

Reference Type: BACKGROUND

"Porter J, et al. Interim Results From a Phase 2A, Open-Label, Dose-Finding Study To Determine The Safety, Efficacy, And Tolerability of Sotatercept (ACE-001) In Adults with Beta-Thalassemia. Presented at the 19thCongress of the European Hematology Association, June 12-15, 2015, Milan, Italy. Abstract No. S622 "

Reference Type: BACKGROUND

Related Links

https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

BMS Clinical Trial Information

https://www.bmsstudyconnect.com/us/en/home.html

BMS Clinical Trial Patient Recruiting

Other Identifiers

2011-005659-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ACE-011-B-THAL-001

Identifier Type: -

Identifier Source: org_study_id