ACE-536 Extension Study - Myelodysplastic Syndromes
Study Details
Study Description
Brief Summary
Study A536-05 is an open-label extension study for patients previously enrolled in study A536-03 (ClinicalTrials.gov Identifier NCT01749514), to evaluate the long-term safety and tolerability of ACE-536 in patients with low or intermediate-1 risk MDS.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Study A536-05 is an open-label extension study to evaluate the safety, tolerability, and pharmacodynamic effects of up to 24 months of ACE-536 treatment in patients with low or intermediate-1 risk myelodysplastic syndromes previously treated with ACE-536 for up to 3 months in study A536-03 (ClinicalTrials.gov Identifier NCT01749514). The starting dose level in study A536-05 will be 1.0 mg/kg by subcutaneous (SC) injection every 3 weeks. Dose titration/modification rules will be followed for individual patients and will be based upon safety and efficacy data collected during the course of treatment.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ACE-536 ACE-536 1.0 mg/kg once every 3 weeks by subcutaneous injection. |
Drug: ACE-536
ACE-536 1.0 mg/kg once every 3 weeks by subcutaneous injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- To evaluate the long-term safety and tolerability of ACE-536 in patients with low or intermediate-1 risk MDS who were previously enrolled in study A536-03 [From first dose (Study Day1) to end of treatment (Study Day 730)]
Secondary Outcome Measures
- Erythroid response in non-transfusion dependent (NTD) patients [From first dose (Study Day1) to end of treatment (Study Day 730)]
Proportion of patients with a mean hemoglobin (Hgb) increase ≥ 1.5 g/dL over an 8-week period as compared to baseline, not influenced by red blood cell (RBC) transfusion
- Rates of erythroid, neutrophil and platelet (HI-E, HI-N and HI-P) responses. [Measured during any 8 week period on study, up to 28 weeks from patient screening, compared with the 8-week period prior to study day 1.]
- Erythroid response in transfusion dependent (TD) patients [From first dose (Study Day1) to end of treatment (Study Day 730)]
Proportion of patients with a decrease of ≥ 4 units or ≥ 50% of units of red blood cells (RBCs) transfused over a period of 8 weeks, relative to the 8 weeks immediately prior to Day 1
- Proportion of TD patients who become transfusion independent [From first dose (Study Day1) to end of treatment (Study Day 730)]
Defined as patients requiring no RBC transfusion for a period of ≥ 8 weeks
- Time to, and duration of, erythroid response in NTD and TD patients [From first dose (Study Day1) to end of treatment (Study Day 730)]
- Mean mean change in RBC transfusion burden (#RBC units/8 weeks) in TD patients [From first dose (Study Day1) to end of treatment (Study Day 730)]
- Mean change in hemoglobin levels in NTD patients [From first dose (Study Day1) to end of treatment (Study Day 730)]
- ACE-536 pharmacokinetic profile (Tmax, Cmax and AUC) [From first dose (Study Day1) to end of treatment (Study Day 730)]
- Change from baseline in markers of erythropoiesis [From first dose (Study Day1) to end of treatment (Study Day 730)]
- Change from baseline in markers of iron metabolism [From first dose (Study Day1) to end of treatment (Study Day 730)]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Completion of the treatment period in the base study A536-03 (ClinicalTrials.gov
Identifier:
NCT01749514)
-
Adequate birth control measures
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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 A536-03 and cannot directly roll over to A536-05) must also meet the following criteria:
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Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic myelomonocytic leukemia (CMML) according to the World Health Organization (WHO) criteria 2 (white blood count (WBC) < 13,000/μL) that meets International Prognostic Scoring System (IPSS) classification (Appendix 2) 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;
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Anemia defined as:
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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
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Transfusion Dependent (TD), defined as having received ≥ 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1.
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Platelet count ≥ 30 x 109/L
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Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia)
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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
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Prior treatment with azacitidine or decitabine
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Treatment within 28 days prior to Cycle 1 Day 1 with:
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an erythropoiesis-stimulating agent (ESA),
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Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF),
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Lenalidomide
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Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1
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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
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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
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Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV)
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Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 150 mm Hg or diastolic blood pressure (DBP) ≥ 100 mm Hg
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Pregnant or lactating females
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History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug
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Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Acceleron Investigative Site | Dresden | Germany |
Sponsors and Collaborators
- Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- A536-05
- 2014-001280-13