Phase 2
Completed N=75
Extension Study to Evaluate Long-Term Effects of Luspatercept in Patients With Myelodysplastic Syndromes (MDS) (A536-05/MK-6143-003)
Source: ClinicalTrials.gov NCT02268383 ↗Enrolled (actual)
75
Serious AEs
38.2%
Results posted
Jul 2024
Primary outcomePrimary: Number of Participants Who Experienced an Adverse Event (AE) — 75 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced an Adverse Event (AE) |
75 | — |
| PRIMARY Number of Participants Who Discontinued Study Treatment Due to an AE |
23 | — |
| SECONDARY Percentage of Participants With Modified Erythroid Response (mHI-E) Per International Working Group (IWG) 2006 Response Criteria |
81.3 | — |
| SECONDARY Rate of Erythroid Response (HI-E) Per IWG 2006 Response Criteria |
80.0 | — |
| SECONDARY Rate of Neutrophil Response (HI-N) Per IWG 2006 Response Criteria |
64.3 | — |
| SECONDARY Rate of Platelet Response (HI-P) Per IWG 2006 Response Criteria |
36.4 | — |
| SECONDARY Duration of HI-E in LTB Participants Per IWG 2006 Response Criteria |
299 | — |
| SECONDARY Duration of HI-E in HTB Participants Per IWG 2006 Response Criteria |
328 | — |
| SECONDARY Time to HI-E in LTB Participants Per IWG 2006 Response Criteria |
83 | — |
| SECONDARY Time to HI-E in HTB Participants Per IWG 2006 Response Criteria |
13 | — |
| SECONDARY Rate of RBC Transfusion Independence (RBC-TI) |
64.3 | — |
| SECONDARY Mean Change From Baseline to Week 8 in RBC Transfusion Burden (TB) in HTB Participants |
-4.4 | — |
| SECONDARY Mean Change From Baseline to Week 8 in Hemoglobin Levels ≥1.5 Grams/dL in LTB Participants |
2.4 | — |
| SECONDARY Serum Concentration of Luspatercept |
0.509; 6.373; 6.589; 7.154; 8.136; 8.227 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Serum Iron |
20.38 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Total Iron Binding Capacity (TIBC) |
-11.37 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Transferrin |
-11.34 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Soluble Transferrin Receptor |
11.52 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Serum Ferritin |
71.61 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Non-Transferrin Bound Iron (NTBI) |
— | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Serum Hepcidin |
— | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Serum Erythropoietin |
2252.15 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Reticulocyte Count |
78.70 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Nucleated RBC (nRBC) Count |
— | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Direct Bilirubin Level |
110.53 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Total Bilirubin Level |
72.17 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Lactate Dehydrogenase Level |
22.98 | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Serum Bone-Specific Alkaline Phosphatase (BSAP) |
— | — |
| SECONDARY Percent Change From Baseline to Day 1853 in Concentration of Serum Cross-Linked C-Telopeptide of Type I Collagen (CTX) |
— | — |
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Data sourced from ClinicalTrials.gov (NCT02268383). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.