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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

30 Apr 2025 → ongoing

Decision date (initial)

2025-04-03

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2024-516009-22-00

WHO UTN

U1111-1294-1414

ClinicalTrials.gov

NCT06499285

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Pharmacokinetic, Safety, Pharmacodynamic

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

Secondary objectives 2

1. 1. To evaluate the efficacy of elritercept in reducing RBC transfusions over longer intervals and/or in participants with high-transfusion burden (HTB)
2. 2. To assess the safety and tolerability of elritercept

Conditions and MedDRA coding

myelodysplastic neoplasms/syndromes (MDS)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information and/or protected personal data in accordance with national and local study participant data protections and privacy regulations.
2. 2. Male or female ≥ 18 years of age at the time of signing informed consent.
3. 3. Diagnosis of MDS with or without RS (as determined in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader) according to WHO 2016 classification that meets the IPSS-R classification of very low, low, or intermediate risk MDS.
4. 4. 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.
5. 5. Refractory or intolerant to prior ESA treatment (discontinued ≥ 4 weeks before randomization), or unlikely to respond to ESA treatment
6. 6. Less than 5% blasts in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader
7. 7. Eastern Cooperative Oncology Group performance status of 0 to 2
8. 8. Females of childbearing potential and sexually active males must agree to use adequate methods

Exclusion criteria 27

1. 1. Del(5q) MDS or therapy-related (secondary) MDS
2. 2. Anemia due to any other known cause (e.g., thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate).
3. 3. Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks before randomization.
4. 4. Clinically significant cardiovascular disease
5. 5. Known ejection fraction < 35%, confirmed by a local echocardiogram performed during Screening, or other assessment performed echocardiogram if collected within 6 months before Screening
6. 6. Child-Pugh class C hepatic impairment
7. 7. Stroke, deep vein thrombosis, or pulmonary embolism within 6 months before Screening
8. 8. Any known history of AML
9. 9. 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.
10. 11. Active infection requiring intravenous treatment (e.g., antibiotics, antifungals, or antivirals) within 28 days, or oral treatment within 14 days before randomization.
11. 12. History of or known active or chronic infection with HIV, hepatitis B virus (HBV), or 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.
12. 13. Body mass index ≥ 40 kg/m2
13. 14. Major surgery within 28 days before randomization
14. 16. Prior use of elritercept, luspatercept, sotatercept.
15. 17. Prior use of hypomethylating agents (HMA), isocitrate dehydrogenase inhibitor, lenalidomide, imetelstat, or immune-suppressive therapy given for treatment of MDS
16. 18. Iron chelation therapy initiated within 8 weeks before randomization. Participants on stable doses of iron chelation therapy for ≥ 8 weeks are allowed
17. 19. 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
18. 24. Serum EPO level ≥ 500 U/L
19. 25. Platelet count ≥ 450 × 109/L or ≤ 25 × 109/L
20. 26. Absolute neutrophil count ≤ 500/μL
21. 27. Serum aspartate aminotransferase or alanine aminotransferase ≥ 3 × the upper limit of normal
22. 28. Total bilirubin ≥ 2 × ULN unless attributable to Gilbert's syndrome
23. 29. Ferritin ≤ 50 μg/L
24. 30. Folate ≤ 2.0 ng/mL
25. 31. Vitamin B12 ≤ 200 pg/mL
26. 32. Estimated glomerular filtration rate < 30 mL/min/1.73m2 as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
27. 33. Pregnant or lactating female

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants achieving transfusion independence (TI) for ≥ 8 weeks from baseline through week 24

Secondary endpoints 4

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

500 Kendall Street

City

Cambridge

Postcode

02142-1108

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Leopold Sellner

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 20

Locations

11 EU/EEA countries · 55 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 174 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications