ACE-536 Extension Study - Myelodysplastic Syndromes

Myelodysplastic Syndromes Clinical Trial

Official title:

An Open-Label Extension Study to Evaluate the Long-Term Effects of ACE-536 for the Treatment of Anemia in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Previously Enrolled in Study A536-03

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02268383
• Other study ID #: A536-05
• Secondary ID: 2014-001280-13
• Status: Completed
• Phase: Phase 2
• Start date: October 2014
• Est. completion date: May 18, 2020

Study information

• Verified date: April 2021
• Source: Acceleron Pharma Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: May 18, 2020
• Est. primary completion date: May 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Completion of the treatment period in the base study A536-03 (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 A536-03 and cannot directly roll over to A536-05) 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 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;

• 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

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• ACE-536
ACE-536 1.0 mg/kg once every 3 weeks by subcutaneous injection

Locations

Country	Name	City	State
Germany	Acceleron Investigative Site	Dresden

Sponsors (1)

Lead Sponsor	Collaborator
Acceleron Pharma Inc.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Erythroid response in non-transfusion dependent (NTD) patients	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	From first dose (Study Day1) to end of treatment (Study Day 730)
Secondary	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.
Secondary	Erythroid response in transfusion dependent (TD) patients	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	From first dose (Study Day1) to end of treatment (Study Day 730)
Secondary	Proportion of TD patients who become transfusion independent	Defined as patients requiring no RBC transfusion for a period of = 8 weeks	From first dose (Study Day1) to end of treatment (Study Day 730)
Secondary	Time to, and duration of, erythroid response in NTD and TD patients		From first dose (Study Day1) to end of treatment (Study Day 730)
Secondary	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)
Secondary	Mean change in hemoglobin levels in NTD patients		From first dose (Study Day1) to end of treatment (Study Day 730)
Secondary	ACE-536 pharmacokinetic profile (Tmax, Cmax and AUC)		From first dose (Study Day1) to end of treatment (Study Day 730)
Secondary	Change from baseline in markers of erythropoiesis		From first dose (Study Day1) to end of treatment (Study Day 730)
Secondary	Change from baseline in markers of iron metabolism		From first dose (Study Day1) to end of treatment (Study Day 730)

External Links

•   Results Posting for Protocol A536-05 EudraCT 2014-001280-13