Extension Study to Evaluate the Safety and Efficacy of Luspatercept in Participants With β-Thalassemia Previously Enrolled in A536-04 (A536-06/MK-6143-004)

Acceleron Pharma

Status and phase: Completed; Phase 2

Conditions: β-Thalassemia

Treatments: Drug: luspatercept

Study type: Interventional

Funder types: Industry

Identifiers

NCT02268409

A536-06

MK-6143-004 (Other Identifier)

2014-001281-94 (EudraCT Number)

Details and patient eligibility

About

Study A536-06 (MK-6143-004) is an open-label extension study for participants previously enrolled in study A536-04 (NCT01749540), to evaluate the long-term safety and tolerability of luspatercept in adult participants with beta-thalassemia.

Enrollment: 51 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Completion of the treatment period in the base study A536-04.
• Females of child- bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal ≥24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 12 weeks following the last dose of study drug
• Males must agree to use a latex condom during any sexual contact with females of child-bearing potential during study participation and for 12 weeks following the last dose of study drug, even if he has undergone a successful vasectomy
• Participants must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of study drug
• Participants with treatment interruption (defined as participants who complete the end of study visit for study A536-04 and are ≥28 days post end of study visit) must also meet the following criteria:
• Mean hemoglobin concentration <10.0 g/dL of 2 measurements (not influenced by red blood cell [RBC] transfusion) (one performed within one day prior to first dose of study treatment and the other performed during the screening period [Day -28 to Day -1]) in non-transfusion dependent (NTD) participants
• Adequate folate levels or on folate therapy
• Platelet count ≥100 x 10^9/L and ≤1,000 x 10^9/L
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3 x upper limit of normal (ULN)
• Serum creatinine ≤ 1.5 x ULN
• Ejection fraction ≥50% by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA)

Exclusion Criteria:

• Discontinuation/withdrawal from study A536-04 due to participant request, participant unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication (e.g., hydroxyurea), medical reason or adverse event, hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up prior to completion of the treatment period
• Any clinically significant pulmonary (including pulmonary hypertension), cardiovascular, endocrine, neurologic, hepatic, gastrointestinal, infectious, immunological (including clinically significant allo- or auto-immunization) or genitourinary disease considered by the investigator as not adequately controlled prior to the first dose of study trearment
• Symptomatic splenomegaly
• Splenectomy within 56 days prior to the first dose of study treatment
• Major surgery (except splenectomy) within 28 days prior to the first dose of study treatment. Participants must have completely recovered from any previous surgery prior to the first dose of study treatment
• Participants receiving or planning to receive hydroxyurea treatment. Participants must not have had hydroxyurea within 90 days of the first dose of study treatment
• For participants with treatment interruption: Iron chelation therapy if initiated within 56 days prior to the first dose of study treatment
• Cytotoxic agents, systemic corticosteroids, immunosuppressants, or anticoagulant therapy such as warfarin or heparin within 28 days prior to the first dose of study treatment (prophylactic aspirin up to 100 mg/day and low molecular weight (LMW) heparin for superficial vein thrombosis (SVT) is permitted)
• Treatment with another investigational drug (including sotatercept [ACE-011]) or device, or approved therapy for investigational use ≤28 days prior to the first dose of study treatment, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to the first dose of study treatment, whichever is longer at any time between the end of treatment of the base study A536-04 and the first dose of study treatment
• Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B virus (HBV) or active infectious hepatitis C virus (HCV)
• Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥150 mm mercury (Hg) or diastolic blood pressure (DBP) ≥100 mm Hg
• Known history of thromboembolic events ≥Grade 3 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0
• Pregnant or lactating females
• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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51 participants in 1 patient group

Luspatercept Extension Population

Experimental group

Description:

Participants receive luspatercept 0.6, 0.8, 1.0, or 1.25 mg/kg administered by subcutaneous injection on Day 1 of each 21-day cycle for up to 87 cycles (up to approximately 5 years). Participants will receive the highest tolerated dose level of luspatercept that they were assigned in the base study unless a dose modification was required.

Treatment:

Drug: luspatercept