Extension Study to Evaluate Long-Term Effects of Luspatercept in Patients With Myelodysplastic Syndromes (MDS) (A536-05/MK-6143-003)

NCT02268383 | Completed Phase 2 Results

• 3 other identifiers: A536-05MK-6143-0032014-001280-13
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label extension study for participants previously enrolled in study MK-6143-001 (formerly called A536-03, ClinicalTrials.gov Identifier NCT01749514), to evaluate the long-term safety and tolerability of luspatercept (MK-6143) in participants with low or intermediate-1 risk MDS.

Conditions

Myelodysplastic Syndromes

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 does not necessarily have a causal relationship with this treatment. An AE can therefore be 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 is considered related to the study drug. The number of participants who experienced an AE was reported.

  Up to approximately 5 years

• 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 does not necessarily have a causal relationship with this treatment. An AE can therefore be 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 is considered related to the study drug. The number of participants who discontinued luspatercept due to an AE was reported.

  Up to approximately 5 years

Secondary Outcomes (27)

• Percentage of Participants With Modified Erythroid Response (mHI-E) Per International Working Group (IWG) 2006 Response Criteria

  Any consecutive 8 weeks during the study (up to approximately 5 years)

• Rate of Erythroid Response (HI-E) Per IWG 2006 Response Criteria

  Any consecutive 8 weeks during the study (up to approximately 5 years)

• Rate of Neutrophil Response (HI-N) Per IWG 2006 Response Criteria

  Any consecutive 8 Weeks during the study (up to approximately 5 years)

• Rate of Platelet Response (HI-P) Per IWG 2006 Response Criteria

  Any consecutive 8 Weeks during the study (up to approximately 5 years)

• Duration of HI-E in LTB Participants Per IWG 2006 Response Criteria

  up to approximately 5 years

Study Arms (1)

Luspatercept Extension population

EXPERIMENTAL

Luspatercept 1.0 mg/kg once every 3 weeks by subcutaneous injection.

Drug: Luspatercept

Interventions

Luspatercept DRUG

Luspatercept 1.0 mg/kg once every 3 weeks by subcutaneous injection.

Also known as: MK-6143, ACE-536

Luspatercept Extension population

Eligibility Criteria

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

You may qualify if:

• Completion of the treatment period in the base study MK-6143-001 (ClinicalTrials.gov Identifier: NCT01749514)
• Adequate birth control measures
• Patient is able to adhere to the study visit schedule, understand and comply with all protocol requirements
• Patient understands and is able to provide written informed consent
• In addition, patients with treatment interruption (defined as patients who complete their end-of-study visit in MK-6143-001 and cannot directly roll over to MK-6143-003) must also meet the following criteria:
• Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic myelomonocytic leukemia (CMML) according to the World Health Organization (WHO) criteria 16 (white blood count (WBC) \< 13,000/μL) that meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC) obtained during screening;
• Anemia defined as:
• Mean hemoglobin concentration \< 10.0 g/dL of 2 measurements (one performed within one day prior to Cycle 1 Day 1 and the other performed 7-28 days prior to Cycle 1 Day 1), for non-transfusion dependent (NTD) patients (defined as having received ˂ 4 units of red blood cells (RBCs) within 8 weeks prior to Cycle 1 Day 1), OR
• Transfusion Dependent (TD), defined as having received ≥ 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1
• Platelet count ≥ 30 x 109/L
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia)
• Adequate renal (creatinine ≤ 2.0 x upper limit of normal \[ULN\]) and hepatic (total bilirubin \< 2 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN) function

You may not qualify if:

• Discontinuation/withdrawal from the base study A536-03 (due to patient request, patient unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication \[e.g. azacitidine\], medical reason or adverse event (AE), hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up) prior to completion of the treatment period
• Prior treatment with azacitidine or decitabine
• Treatment within 28 days prior to Cycle 1 Day 1 with:
• An erythropoiesis-stimulating agent (ESA),
• Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF),
• Lenalidomide
• Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1
• Treatment with another investigational drug (including sotatercept \[ACE-011\]) or device, or approved therapy for investigational use ≤ 28 days prior to Cycle 1 Day 1, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer
• Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1
• Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV)
• Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 150 mm Hg or diastolic blood pressure (DBP) ≥ 100 mm Hg
• Pregnant or lactating females
• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug
• Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study

Sponsors & Collaborators

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

Study Sites (1)

Acceleron Investigative Site

Dresden, Germany

Location

Related Publications (2)

• Platzbecker U, Gotze KS, Kiewe P, Germing U, Mayer K, Radsak M, Wolff T, Chromik J, Sockel K, Oelschlagel U, Haase D, Illmer T, Al-Ali HK, Silling G, Reynolds JG, Zhang X, Attie KM, Shetty JK, Giagounidis A. Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study. J Clin Oncol. 2022 Nov 20;40(33):3800-3807. doi: 10.1200/JCO.21.02476. Epub 2022 Aug 23.

  PMID: 35998303 DERIVED

• Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, Radsak M, Wolff T, Zhang X, Laadem A, Sherman ML, Attie KM, Giagounidis A. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017 Oct;18(10):1338-1347. doi: 10.1016/S1470-2045(17)30615-0. Epub 2017 Sep 1.

  PMID: 28870615 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

luspatercept

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

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 9, 2014
• Primary Completion: March 19, 2020
• Study Completion: March 19, 2020
• Last Updated: July 29, 2024
• Results First Posted: July 29, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)