The Efficacy and Safety of Elritercept in Adult Participants With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) With Anemia (RENEW)

Trial Title: The Efficacy and Safety of Elritercept in Adult Participants With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) With Anemia (RENEW)

NCT ID: NCT06499285

Condition: Myelodysplastic Syndromes

Conditions: Official terms:
Preleukemia
Myelodysplastic Syndromes
Syndrome

Study type: Interventional

Study phase: Phase 3

Overall status: Not yet recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: Participants will be randomly assigned in a 2:1 ratio to receive either KER-050 or placebo subcutaneously every 4 weeks.

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Intervention:

Intervention type: Biological
Intervention name: KER-050
Description: KER-050 administered subcutaneously every 4 weeks
Arm group label: Experimental: KER-050 (N=150)

Intervention type: Drug
Intervention name: Placebo
Description: Placebo administered subcutaneously every 4 weeks
Arm group label: Placebo Comparator (N=70)

Summary: KER-050-D301 is a Phase 3, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of KER-050 versus placebo in adult participants with transfusion-dependent anemia with very low, low, or intermediate risk MDS, or more recently defined as myelodysplastic neoplasms, with or without ring sideroblasts. The study is divided into the Screening Period, Treatment Period, Safety Follow-Up Period and Long-term Follow-up Period.

Detailed description: This is a Phase 3, double-blind, randomized, placebo-controlled study of KER-050 where participants will be randomized and enter the Primary Phase of the Double-blind Treatment Period. Participants will be randomly assigned in a 2:1 ratio to receive either KER-050 or placebo subcutaneously (SC) every 4 weeks (Q4W). Participants will be stratified according to their RS status (RS-positive versus non-RS) and baseline transfusion burden (LTB versus HTB) during the Screening Period. The Primary Phase of the Double-blind Treatment Period will last up to 24 weeks. Study visits will occur approximately every 2 weeks during the first 24 weeks and approximately every 4 weeks thereafter. For participants to remain on double-blind treatment, they must meet the criteria outlined in the MDS disease assessment criteria every 24 weeks. Based on the outcome of the Week 24 MDS disease assessment, participants will either continue in the Extension Phase of the Double-blind Treatment Period or will be discontinued from treatment and proceed to End of Treatment and then into the Safety Follow-up Period.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Male or female ≥ 18 years of age at the time of signing informed consent. - Diagnosis of MDS with or without RS (as determined in an evaluable bone marrow aspirate, read by an independent central reader to confirm diagnosis at Screening) according to the World Health Organization 2016 classification that meets the IPSS-R classification of very low, low, or intermediate risk disease. - Transfusion-dependent anemia assessed over two 8-week periods (i.e., 16 weeks) immediately preceding randomization, classified as either: 1. LTB: average of 2 to < 4 RBC units per 8 weeks with at least 1 transfusion event in each 8-week period and 2 to < 4 RBC units in the 8 weeks immediately preceding randomization, or 2. HTB: average of ≥ 4 RBC units per 8 weeks with at least 1 transfusion event in each 8-week period and ≥ 4 RBC units in the 8 weeks immediately preceding randomization, and 3. For all participants: i. Only transfusion events for Hgb < 9 g/dL are counted toward eligibility. ii. A minimum of 2 transfusion events must occur that are separated by ≥ 7 days within the 16-week period immediately preceding randomization. iii. No consecutive 56-day period can be RBC transfusion-free during the 16-week period immediately preceding randomization. - Refractory or intolerant to prior ESA treatment, or is unlikely to respond to ESA treatment - < 5% blasts in an evaluable bone marrow aspirate - Eastern Cooperative Oncology Group performance status of 0-2 - Females of childbearing potential and sexually active males must agree to use highly effective methods of contraception Exclusion Criteria: - Del(5q) MDS or secondary MDS. - Anemia due to any other known cause (e.g., thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate). - Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks before randomization. - Clinically significant cardiovascular disease - Known ejection fraction < 35%, confirmed by a local echocardiogram or other assessment performed within 6 months before Screening - Child-Pugh class C hepatic impairment - Stroke, deep vein thrombosis, or pulmonary embolism within 6 months before Screening - Any known history of AML - Prior history of malignancies, other than MDS, unless participant has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years History of solid organ or bone marrow transplantation - Active infection requiring intravenous antibiotics within 28 days or oral antibiotics within 14 days before randomization - Known HIV, active hepatitis B virus (HBV), or active hepatitis C virus (HCV) infection - Body mass index ≥ 40 kg/m2 - Major surgery within 28 days before randomization - Prior lifetime use of TGF-β-modulating therapy, including luspatercept, sotatercept, or any investigational or commercially available TGF-β-modulating therapy - Prior lifetime use of HMA, isocitrate dehydrogenase inhibitor, lenalidomide, imetelstat, or immune-suppressive therapy given for treatment of MDS - Iron chelation therapy initiated within 8 weeks before randomization. Participants on stable doses of iron chelation therapy for ≥ 8 weeks are allowed - Vitamin B12 therapy initiated within 4 weeks before randomization. Participants on stable replacement doses for ≥ 4 weeks and without concurrent vitamin B12 or folate deficiency are allowed - Serum EPO level ≥ 1000 U/L - Platelet count ≥ 450 × 109/L or ≤ 50 × 109/L - Absolute neutrophil count ≤ 500/mL - Serum aspartate aminotransferase or alanine aminotransferase ≥ 3 × the upper limit of normal - Total bilirubin ≥ 2 × ULN unless attributable to Gilbert's syndrome - Ferritin ≤ 50 μg/L - Folate ≤ 4.5 nmol/L (≤ 2.0 ng/mL) - Vitamin B12 ≤ 148 pmol/L (≤ 200 pg/mL) - Estimated glomerular filtration rate < 40 mL/min/1.73m2 as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (National Kidney Foundation 2021; Delgado 2022) - Pregnant or lactating female

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: December 31, 2024

Completion date: March 14, 2032

Lead sponsor:
Agency: Keros Therapeutics, Inc.
Agency class: Industry

Source: Keros Therapeutics, Inc.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06499285