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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01571635
First Posted: April 5, 2012
Last Update Posted: January 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Celgene
  Purpose
Dose finding study to determine the safety and tolerability of Sotatercept (ACE-011) in adults with Beta (β)-Thalassemia

Condition Intervention Phase
Beta Thalassemia Major Beta Thalassemia Intermedia Drug: Sotatercept 0.1mg/kg Drug: Sotatercept 0.3mg/kg Drug: Sotatercept 0.5mg/kg Drug: Sotatercept 0.75mg/kg Drug: Sotatercept 1.0mg/kg Drug: Sotatercept 1.5mg/kg Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Celgene:

Primary Outcome Measures:
  • Potential Recommended Dose (PRD) [ Time Frame: Up to 27 months ]
    The potential recommended dose (PRD) will be determined following the assessment of efficacy and safety parameters based on the first three doses of Sotatercept administered, up to at least 21 days following the first dose, for all doses evaluated. The PRD of Sotatercept will be defined as the highest dose level at which no more than one out of six subjects experiences a dose-limiting toxicity (DLT). The recommended dose of Sotatercept will be defined based on the review of the efficacy and safety parameters as well as dose modification data. The efficacy parameter is defined as: - for transfusion dependent B-Thalassemia major and intermedia : the reduction of transfusion burden by ≥ 20% compared to the calculated baseline transfusion burden to each subject ; - for non-transfusion dependent B-Thalassemia intermedia subjects : increase in Hgb level by ≥ 1 g/dl compared to the baseline Hgb, sustained for 12 weeks.

  • Actual Recommended Dose (RD) [ Time Frame: Up to 27 months ]
    The RD of Sotatercept will be defined based on the review of the efficacy and safety parameters as well as dose modification data. The efficacy parameter is defined as: - for transfusion dependent B-Thalassemia major and intermedia : the reduction of transfusion burden by ≥ 20% compared to the calculated baseline transfusion burden to each subject ; - for non-transfusion dependent B-Thalassemia intermedia subjects : increase in Hgb level by ≥ 1 g/dl compared to the baseline Hgb, sustained for 12 weeks.


Secondary Outcome Measures:
  • Reduction of Transfusion Burden [ Time Frame: Up to 27 months ]
    Assess the reduction of transfusion burden in transfusion dependent Beta-Thalassemia major and Intermedia subjects.

  • Number of Participants with Adverse Events [ Time Frame: Up to 27 months ]
    Number of participants with adverse events

  • PK-Observed Maximum Concentration (Cmax) [ Time Frame: Up to 16 samples over 27 months ]
    PK-observed maximum concentration (Cmax)

  • PK-Time to Maximum Concentration (Tmax) [ Time Frame: Up to 16 samples over 27 months ]
    PK-Time to maximum concentration (Tmax)

  • PK-Area Under the Concentration-Time Curve (AUC) [ Time Frame: Up to 16 samples over 27 months ]
    PK-Area under the concentration-time curve (AUC)

  • PK-Concentration of Anti-Sotatercept Antibody in Serum [ Time Frame: Up to 16 samples over 27 months ]
    PK-Concentration of anti-sotatercept antibody in serum

  • Hgb Level Increase [ Time Frame: Up to 27 months ]
    To assess the Hgb level increase from baseline in non-transfusion dependent Beta Thalassemia intermedia subjects.


Enrollment: 46
Study Start Date: October 2012
Estimated Study Completion Date: February 2020
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: Sotatercept 0.1mg/kg
Experimental: 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
Drug: Sotatercept 0.3mg/kg
Experimental: 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
Drug: Sotatercept 0.5mg/kg
Experimental: 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
Drug: Sotatercept 0.75mg/kg
Experimental: 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
Drug: Sotatercept 1.0mg/kg
Experimental: 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
Drug: Sotatercept 1.5mg/kg

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01571635


Locations
France
Hopital Henri Mondor
Créteil, France, 94010
Hospital of Necker
Paris, France, 75 PARIS 15ème
Greece
Laiko General Hospital
Ampelokipi - Athens, Greece, 11526
Italy
Universita degli Studi di Cagliari - ASL8
Cagliari, Italy, 09121
Ospedale Galliera
Genoa, Italy, 16128
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Milano, Italy, 20122
United Kingdom
UCL Cancer Institute
London, United Kingdom, WC1E 6BT
Sponsors and Collaborators
Celgene
Investigators
Study Director: Abderrahmanne Laadem, CRP Celgene
  More Information

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01571635     History of Changes
Other Study ID Numbers: ACE-011-B-THAL-001
2011-005659-15 ( EudraCT Number )
First Submitted: April 3, 2012
First Posted: April 5, 2012
Last Update Posted: January 20, 2017
Last Verified: January 2017

Keywords provided by Celgene:
Beta-Thalassaemia

Additional relevant MeSH terms:
Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn