A phase 3 trial comparing elritercept versus epoetin alfa for treatment of anemia due to lower-risk MDS in ESA-naïve adults who require RBC transfusions

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]

Decision date (initial)

2026-04-21

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Takeda Development Center Americas, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Pharmacokinetic, Efficacy, Safety

To evaluate the efficacy of elritercept on red blood cell transfusion independence (RBC-TI) for a minimum 12-week period within 24 weeks with concurrent mean hemoglobin (Hgb) increase ≥1.5 g/dL compared to epoetin alfa

Secondary objectives 4

1. Key Secondary Objective: To compare the effect of elritercept on RBC-TI for a minimum 16-week period within 24 weeks versus epoetin alfa.
2. Key Secondary Objective: To compare effect of elritercept on RBC-TI for a minimum 12-week period within 24 weeks versus epoetin alfa.
3. Key Secondary Objective: To compare the effect of elritercept on RBC-TI for a minimum 24-week period within 24 weeks versus epoetin alfa.
4. For further information please refer to the Protocol

Conditions and MedDRA coding

Myelodysplastic neoplasms/syndromes (MDS)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male or female participants aged ≥18 years or older at time of signing the informed consent form (ICF).
2. Able to understand the purpose and risks of the trial and voluntarily sign an ICF prior to any trial-related procedures being conducted and authorization to use protected health information and personal data in accordance to national and local privacy regulations.
3. Documented diagnosis of myelodysplastic syndrome(s) (MDS) according to WHO 2016 classification that meets International Prognostic Scoring System – Revised (IPSS-R) classification of very low-, low-, or intermediate-risk disease, confirmed by central laboratory independent reviewer prior to randomization. Hemoglobin (Hgb), platelet, and absolute neutrophil count (ANC) values should be collected >14 days after red blood cell (RBC) transfusion or >7 days after platelet transfusion, unless otherwise considered to be pretransfusion values.
4. Bone marrow <5% blasts in an evaluable bone marrow collected at screening and confirmed by central pathology independent reviewer.
5. Endogenous serum erythropoietin s (EPO) level of <500 U/L. Should be results from blood samples collected >14 days following an RBC transfusion to evaluate for eligibility unless considered pretransfusion values.
6. Participant requires RBC transfusion, as documented by the following criteria (Section 8.1.1.3). A transfusion requirement of 2 to 6 packed red blood cells (pRBCs) units/8 weeks confirmed for a minimum of 8 weeks immediately preceding randomization. • Hgb levels at the time of or within 3 days prior to administration of a RBC transfusion must have been ≤9.0 g/dL (5.6 mmol/L) with symptoms of anemia (or ≤7 g/dL [4.3 mmol/L] in the absence of symptoms) in order for the transfusion to be counted towards meeting eligibility criteria. • RBC transfusions administered when Hgb levels were >9.0 g/dL (or >7 g/dL in the absence of symptoms) and/or RBC transfusions administered for elective surgery, infections or bleeding events will not qualify as a required transfusion for the purpose of meeting eligibility criteria or stratification.
7. Hgb <11.0 g/dL (6.8 mmol/L) after last RBC transfusion preceding randomization. Local laboratory is acceptable to facilitate randomization.
8. Eastern Cooperative Oncology Group score of 0, 1, or 2.

Exclusion criteria 24

1. Prior therapy with any of the following: a) Epoetin alfa • At the investigator’s discretion in consultation with the medical monitor, may be allowed if received no more than 2 doses of only epoetin alfa ≥8 weeks prior to randomization. No other erythropoiesis-stimulating agent (ESA) agent is allowed. b) Darbepoetin. c) Granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor administered ≤8 weeks (56 days) prior to randomization unless given for treatment of febrile neutropenia. d) Immunomodulatory drug (IMiDs) including lenalidomide. • At the investigator’s discretion in consultation with the medical monitor may be allowed if received ≤1 week of an IMiD ≥8 weeks prior to randomization. e) Hypomethylating agent. • At the investigator’s discretion, in consultation with the medical monitor may be allowed if received no more than 2 doses ≥8 weeks prior to randomization. f) Luspatercept, sotatercept, imetelstat, or elritercept. g) Immunosuppressive therapy. h) Hematopoeitic cell transplant. i) Iron chelation if administered ≤8 weeks prior to randomization. Participants on stable doses of iron chelation therapy for ≥8 weeks are allowed Vitamin B12 or folate therapy initiated within 4 weeks prior to randomization. Participants on stable replacement doses for ≥4 weeks and without ongoing concurrent vitamin B12 or folate deficiency are allowed. j) Androgen use within 8 weeks before randomization. Participants on stable androgen dosing for hypogonadism for ≥8 weeks are allowed. k) High-dose corticosteroid use within 4 weeks before randomization. Participants on stable chronic steroid doses of prednisone ≤10 mg/day or corticosteroid equivalent for ≥4 weeks are allowed. Other disease modifying treatments for autoimmune diseases may be allowed upon medical monitor review. l) Investigational agent or any other agent intended for treatment MDS treatment.
2. Diagnosed to have MDS associated with del(5q) cytogenetic abnormality or MDS unclassifiable according to WHO 2016 classification or secondary MDS.
3. Known history of diagnosis of acute myeloid leukemia (AML).
4. Anemia due to any other known cause including but not limited to thalassemia; hypothyroidism; due to iron, vitamin B12, vitamin B6, zinc, or folate deficiencies; autoimmune or hereditary hemolytic anemia; any type of known clinically significant bleeding or sequestration or drug induced anemia, hemolytic anemia, or bleeding events.
5. Clinically significant cardiovascular disease defined as: a) New York Heart Association heart disease class III or IV. b) Fridericia corrected QT (QTcF) interval >500 milliseconds during screening. c) Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before screening.
6. Known ejection fraction <35%, confirmed by a local echocardiogram performed during screening, or a previously performed echocardiogram if collected within 6 months before screening.
7. Medical history of thromboembolic events within 6 months before screening, including history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (DVT; including proximal and distal), pulmonary or arterial embolism, arterial thrombosis or other venous thrombosis. Participants with prior superficial thrombophlebitis are allowed.
8. Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure of ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg despite adequate treatment.
9. Prior history of malignancies, other than MDS. Participants who are free of other malignant disease for ≥3 years and have completed treatment, including maintenance are allowed. Participants with a history or concurrent diagnosis of the following conditions are allowed if not requiring systemic therapy: a) Basal or squamous cell carcinoma of the skin; b) Carcinoma in situ of the cervix; c) Carcinoma in situ of the breast; and/or d) Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system).
10. History of solid organ or bone marrow transplantation.
11. Active infection requiring intravenous antibiotics within 28 days or oral antibiotics within 14 days before randomization.
12. 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.
13. Body mass index ≥40 kg/m2.
14. Major surgery within 28 days before randomization.
15. New-onset seizures or poorly controlled seizures within 12 weeks prior to randomization are excluded from trial participation.
16. History of allergy/anaphylaxis to investigational product (including epoetin alfa) excipients (refer to the current elritercept investigator’s brochure for a list of excipients) or recombination proteins.
17. History of pure red cell aplasia and/or antibody against erythropoietin (EPO).
18. Any of the following laboratory abnormalities: a) ANC <500/μL (0.5×109/L). b) Platelet count <50,000/μL (50×109/L) or ≥450,000/μL (450×109/L). c) Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3× upper limit of the normal (ULN). d) Total bilirubin ≥2×ULN. Participants with known history of Gilbert syndrome with unconjugated bilirubin <3×ULN are allowed. Higher levels if attributed to active RBC precursor destruction within the bone marrow (ineffective erythropoiesis) may be allowed upon medical monitor review. e) Estimated glomerular filtration rate <30 mL/min/1.73 m2 as determined by the Chronic Kidney Disease Epidemiology (CKD-EPI) collaboration equation (Delgado et al. 2021; Kramer et al. 2022). f) Ferritin ≤50 μg/L. g) Folate ≤2.0 ng/mL. h) Vitamin B12 ≤200 pg/mL.
19. Ongoing participation in another interventional clinical trial or use of any other investigational medicinal product within five times the half-life.
20. Participant is unwilling or in the opinion of the investigator the participant is unable to comply with the requirements of the protocol.
21. Is a participant of childbearing potential (POCBP) but does not agree to use at least 1 form of highly effective contraception from the time of signing the ICF until at least 60 days after the last dose of trial intervention (see Section 13.1 for details).
22. Participants of male birth who are fertile and who have partners of childbearing potential, who do not agree to use acceptable barrier contraception, that is, a male condom during the entire trial intervention period until at least 60 days after the last dose of trial intervention (see Section 13.1 for details).
23. If applicable, participant with a positive serum pregnancy test during the screening period or known to be pregnant or a lactating participant who does not agree to forego breastfeeding during the entire trial intervention period until at least 60 days after the last dose of trial intervention.
24. For Participants in France: Persons under court protection, persons not affiliated with a social security system, and protected adults (per applicable French law [Art. L. 1121-6, Art. L. 1121-8, Art. L. 1121-8-1]).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who are RBC-TI for any consecutive ≥12-week period from Cycle 1 Day 1 (C1D1) through Week 24 with concurrent mean Hgb increase ≥1.5 g/dL from baseline

Secondary endpoints 4

1. Key Secondary Endpoint: Proportion of participants who are RBC-TI for any consecutive ≥16-week period from C1D1 through Week 24.
2. Key Secondary Endpoint: Proportion of participants who are RBC-TI for any consecutive ≥12-week period from C1D1 through Week 24.
3. Key Secondary Endpoint: Proportion of participants who are RBC-TI for a consecutive 24-week period from C1D1.
4. For further details please refer to the Protocol

Investigational products

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

Test 1

Comparator 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

Alexander Vorog

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 14

Locations

14 EU/EEA countries · 57 investigational sites

By country

Investigational sites

Results and documents

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

Documents 96 files

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

Application history

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