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)

NCT02268409 | Completed Phase 2 Results

• 3 other identifiers: A536-06MK-6143-0042014-001281-94
• Study Type: interventional
• Target: 51
• Locations: 2 countries
• Sites: 7

Brief Summary

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.

Conditions

β-Thalassemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced an Adverse Event (AE)

  An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. The number of participants who experienced an AE is reported.

  Up to approximately 68 months

• Number of Participants Who Discontinued Study Treatment Due To an AE

  An adverse event (AE) was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which did not necessarily have a causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. The number of participants who discontinued study treatment due to an AE is reported.

  Up to approximately 60 months

Secondary Outcomes (57)

• Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline Over a Rolling 8-week Interval

  Any 8-week interval during the study (up to approximately 68 months)

• Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline Over a Rolling 12-week Interval

  Any 12-week interval during the study (up to approximately 68 months)

• Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During Weeks 13 to 24

  Weeks 13 to 24

• Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During Weeks 37 to 48

  Weeks 37 to 48

• Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline Over a Rolling 8-week Interval

  Any 8-week interval during the study (up to approximately 68 months)

Study Arms (1)

Luspatercept Extension Population

EXPERIMENTAL

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.

Drug: luspatercept

Interventions

luspatercept DRUG

subcutaneous injection

Also known as: ACE-536, MK-6143

Luspatercept Extension Population

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA: lead

Study Sites (7)

Acceleron Investigative Site

Athens, Greece

Location

Acceleron Investigative Site

Brindisi, Italy

Location

Acceleron Investigative Site

Catania, Italy

Location

Acceleron Investigative Site

Ferrara, Italy

Location

Acceleron Investigative Site

Modena, Italy

Location

Acceleron Investigative Site

Naples, Italy

Location

Acceleron Investigative Site

Turin, Italy

Location

Related Publications (2)

• Piga A, Longo F, Gamberini MR, Voskaridou E, Ricchi P, Caruso V, Pietrangelo A, Zhang X, Shetty JK, Attie KM, Tartaglione I. Long-term safety and erythroid response with luspatercept treatment in patients with beta-thalassemia. Ther Adv Hematol. 2022 Dec 5;13:20406207221134404. doi: 10.1177/20406207221134404. eCollection 2022.

  PMID: 36505885 DERIVED

• Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7.

  PMID: 30617198 DERIVED

MeSH Terms

Interventions

luspatercept

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2014
• First Posted: October 20, 2014
• Study Start: October 20, 2014
• Primary Completion: June 18, 2020
• Study Completion: June 18, 2020
• Last Updated: July 18, 2024
• Results First Posted: July 18, 2024

Record last verified: 2024-02

Locations

GR (1); IT (6)