A study of elritercept to treat transfusion-dependent anemia due to very low, low, or intermediate risk myelodysplastic syndromes

Phase 3

Recruiting

• Conditions: myelodysplastic neoplasms/syndromes (MDS)
• Interventions: Drug: elritercept

• Registration Number: 2024-516009-22-00
• Lead Sponsor: Keros Therapeutics Inc.

Brief Summary

To evaluate the efficacy of elritercept in reducing red blood cell (RBC) transfusions

Detailed Description

This is a Phase 3, double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of KER-050 versus placebo. KER-050 an investigational medicinal product being developed for the treatment of anemia in adult participants with a diagnosis of lower-risk myelodysplastic neoplasms/syndromes. After all required Screening Period assessments are completed, and eligibility is confirmed, 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). The Primary Phase of the Double-blind Treatment Period will last 24 weeks. The Secondary Phase of the Double-Blind Treatment Period will last an additional 24 weeks. During the Secondary Phase of the Double-Blind Treatment Period, all participants will continue to receive the same double-blind treatment they received during the Primary Phase. Study visits will occur approximately every 2 weeks from Cycle 1 through Cycle 6 and every 4 weeks from Cycle 7 through the remainder of the Double-Blind Treatment Period. During the Extension Phase of the Double-Blind Treatment Period, all eligible participants will continue to receive the same double-blind treatment they received during the Primary and Secondary Phases. Participants will continue in the Extension Phase until they individually discontinue or until the study is unblinded. 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. The Safety Follow-Up Period will extend from the last dose of study treatment through 8 weeks after the last dose of study treatment. Study visits should occur every 4 weeks within the Safety Follow-Up Period. Long-term follow-up will take place quarterly after a participant has completed the Safety Follow-Up Period. Long-term follow-up will continue for 5 years from the first dose of study treatment or 3 years after the last dose, whichever is longer, or until a participant is deceased, is lost to follow-up, withdraws consent, or the study closes, whichever is earliest.

Study Timeline

• Study First Posted: 2025-03-28
• Last Update Posted: 2025-06-26

Recruitment & Eligibility

• Status: Authorised, recruiting
• Sex: Not specified
• Target Recruitment: 74

Inclusion Criteria

1. Male or female ≥ 18 years of age at the time of signing informed consent.

2. Diagnosis of MDS with or without RS (as determined in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader to confirm diagnosis) according to WHO 2016 classification that meets the IPSS-R classification of very low, low, or intermediate risk MDS.

3. Transfusion-dependence assessed in the 16 weeks immediately preceding randomization in two 8-week blocks, classified as either: a. LTB, defined as 4 to 7 RBC units per 16 weeks; or b. HTB, defined as ≥ 8 RBC units per 16 weeks; and c. For all participants: - Only transfusion events for a pretransfusion Hgb < 10 g/dL are counted toward eligibility; - At least 1 transfusion event in each 8-week period and a minimum of 2 transfusion events separated by ≥ 7 days within the 16-week period immediately preceding randomization; and - No consecutive 56-day period can be RBC transfusion-free during the 16-week period immediately preceding randomization.

4. Refractory or intolerant to prior ESA treatment (discontinued ≥ 8 weeks before randomization), or unlikely to respond to ESA treatment

5. Less than 5% blasts in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader

6. Eastern Cooperative Oncology Group performance status of 0 to 2

7. Females of childbearing potential and sexually active males must agree to use highly effective methods of contraception

Exclusion Criteria

1. Del(5q) MDS or secondary MDS

2. Active infection requiring intravenous treatment (e.g., antibiotics, antifungals, or antivirals) within 28 days, or oral treatment within 14 days before randomization.

3. Known positive for HIV, active infectious hepatitis B virus (HBV), or active infectious hepatitis C virus (HCV). Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines

4. Body mass index ≥ 40 kg/m2

5. Major surgery within 28 days before randomization

6. Prior use of elritercept, luspatercept, sotatercept.

7. Prior use of hypomethylating agents (HMA), isocitrate dehydrogenase inhibitor, lenalidomide, imetelstat, or immune-suppressive therapy given for treatment of MDS

8. Iron chelation therapy initiated within 8 weeks before randomization. Participants on stable doses of iron chelation therapy for ≥ 8 weeks are allowed

9. Vitamin B12 or folate 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

10. Serum EPO level ≥ 500 U/L

11. Platelet count ≥ 450 × 109/L or ≤ 25 × 109/L

12. Anemia due to any other known cause (e.g., thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate).

13. Absolute neutrophil count ≤ 500/μL

14. Serum aspartate aminotransferase or alanine aminotransferase ≥ 3 × the upper limit of normal

15. Total bilirubin ≥ 2 × ULN unless attributable to Gilbert's syndrome

16. Ferritin ≤ 50 μg/L

17. Folate ≤ 2.0 ng/mL

18. Vitamin B12 ≤ 200 pg/mL

19. Estimated glomerular filtration rate < 40 mL/min/1.73m2 as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation

20. Pregnant or lactating female

21. Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks before randomization.

22. Clinically significant cardiovascular disease

23. Known ejection fraction < 35%, confirmed by a local echocardiogram performed during Screening, or other assessment performed echocardiogram if collected within 6 months before Screening

24. Child-Pugh class C hepatic impairment

25. Stroke, deep vein thrombosis, or pulmonary embolism within 6 months before Screening

26. Any known history of AML

27. Prior history of malignancies, other than MDS, unless participant has been free of the disease (including completion of any treatment, including maintenance, for prior malignancy) for ≥ 5 years.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
elritercept	elritercept	Participants receiving elritercept

Primary Outcome Measures

Name	Time	Method
Proportion of participants achieving transfusion independence (TI) for ≥ 8 weeks from baseline through week 24		Proportion of participants achieving transfusion independence (TI) for ≥ 8 weeks from baseline through week 24

Secondary Outcome Measures

Name	Time	Method
1. Proportion of participants achieving TI for ≥ 24 weeks from baseline through week 48		1. Proportion of participants achieving TI for ≥ 24 weeks from baseline through week 48
2. Proportion of participants with HTB achieving TI for ≥ 8 weeks from baseline through week 24		2. Proportion of participants with HTB achieving TI for ≥ 8 weeks from baseline through week 24
3. Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)		3. Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
4. Change from baseline in clinical laboratory values, vital signs, and electrocardiograms (ECGs)		4. Change from baseline in clinical laboratory values, vital signs, and electrocardiograms (ECGs)

Trial Locations

Locations (46)

Fakultni Nemocnice Brno; 🇨🇿 Brno, Czechia

Institute Of Hematology And Blood Transfusion; 🇨🇿 Prague, Czechia

Fakultni Nemocnice Hradec Kralove; 🇨🇿 Novy Hradec Kralove, Czechia

Fakultni Nemocnice Kralovske Vinohrady; 🇨🇿 Prague, Czechia

Assistance Publique Hopitaux De Paris; 🇫🇷 Paris, France

Centre Hospitalier Universitaire De Nice; 🇫🇷 Nice, France

Centre Hospitalier Universitaire De Toulouse; 🇫🇷 Toulouse Cedex 9, France

Centre Hospitalier Universitaire De Poitiers; 🇫🇷 Poitiers, France

St Vincent's University Hospital; 🇮🇪 Dublin 4, Ireland

Beaumont Hospital; 🇮🇪 Dublin 9, Ireland

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Fakultni Nemocnice Brno

🇨🇿Brno, Czechia

Jiří Mayer

Site contact

+420532233642

mayer.jiri@fnbrno.cz