A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib

Official title

A Phase 3, Double-Blind, Randomized Trial Evaluating the Efficacy and Safety of Elritercept (TAK-226) Compared to Placebo in Participants With Myelofibrosis and Anemia on Concurrent Ruxolitinib Therapy

Overview

The main aim of this study is to find out how well elritercept works to improve anemia in participants with myelofibrosis (MF) who are taking ruxolitinib when compared to placebo. Other aims are to learn how elritercept improves anemia compared to placebo; to learn if elritercept reduces tiredness, improves symptoms related to MF, and helps participants do physical activities more easily. The study also aims to find out how elritercept affects the bone marrow, the spleen, and whether participants develop antibodies to the study drug. The study will also check how safe elritercept is compared to placebo, and if elritercept stays safe over a long period of time. Participants will receive study treatment for at least 9 months (36 weeks). After this period, participants who received placebo will have the option to switch to elritercept.

Interventions

• Drug Placebo
  Elritercept-matching placebo
• Drug Elritercept
  Elritercept, SC, injection

Primary outcome measures

• Proportion of Participants Who Are Red Blood Cell-Transfusion Independent (RBC-TI) for Any Consecutive Greater Than or Equal to (≥) 12-Week Period During the 36-Week Double-Blinded Treatment Period [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]

Secondary outcome measures (12)

• Proportion of Participants Who Achieve ≥50 Percent (%) Reduction in RBC Transfusion Burden From Baseline Over Any Consecutive 12-Week Period [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Proportion of Participants Who Are RBC-TI for Any Consecutive ≥16-Week Period [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Proportion of Participants Who Are RBC-TI for Any Consecutive ≥12-Week Period With Concurrent Mean Hemoglobin (Hgb) Increase ≥1.5 Grams per Deciliter (g/dL) From Baseline [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Proportion of Participants Who Are RBC-TI for Any Consecutive ≥24-Week Period [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Proportion of Participants Who Are RBC-TI for Any Consecutive ≥12-Week Period With Concurrent Mean Hgb Increase of ≥1.0 g/dL and ≥2.0 g/dL From Baseline [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Proportion of Participants Who Are RBC-TI for Any Consecutive 16- or 24-Week Period With a Concurrent Mean Hgb Increase of ≥1.0 g/dL, ≥1.5 g/dL, and ≥2.0 g/dL From Baseline [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Maximum Duration of RBC-TI for Participants Who Achieved RBC-TI for a Consecutive ≥12 Weeks [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Maximum Duration of RBC-TI With Concurrent Mean Hgb Increase of ≥1.5 g/dL for Participants Who Achieved Consecutive ≥12 Weeks RBC-TI With Concurrent Mean Hgb Increase of ≥1.5 g/dL [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Time to Onset of Anemia Response [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]
• Mean Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Fatigue 7a T-Score at Week 36 [Time frame: Baseline, Week 36]
• Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Fatigue Scale Score at Week 36 [Time frame: Baseline, Week 36]
• Proportion of Participants With Meaningful Improvement and Meaningful Deterioration in PROMIS Short Form v1.0 - Fatigue 7a T-score [Time frame: From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)]

Eligibility criteria

Inclusion criteria

• Aged ≥18 years at the time of signing the informed consent form (ICF).
• Able to understand the purpose and risks of the trial and voluntarily sign an ICF.
• Diagnosed with primary myelofibrosis (PMF), post-essential thrombocythemia (post-ET MF) or post-polycythemia vera (post-PV MF) according to the 2022 WHO criteria (WHO Classification of Tumours Editorial Board 2024), confirmed by local pathology report.
• Transfusion status as assessed in the 12 weeks immediately preceding randomization classified as Transfusion Dependent: 3 to 8 RBC units over 12 weeks.
• Receiving ruxolitinib (as approved in the country of the trial site) as the standard of care treatment for MF for at least 12 consecutive weeks, and on a stable daily dose for at least the 8 weeks immediately preceding the date of randomization.
• Eastern Cooperative Oncology Group score less than or equal to (≤) 2.

Exclusion criteria

• Prior treatment with luspatercept, sotatercept, or other transforming growth factor beta inhibitors or activin receptor ligand traps.
• Systemic treatment within 28 days before randomization with any of the following:

• Androgens (including danazol). Participants on stable androgen dosing for hypogonadism for ≥8 weeks are allowed.
• erythropoiesis-stimulating agents.
• granulocyte colony stimulating factor or granulocyte-macrophage colony stimulating factor.
• High dose corticosteroids. Participants on stable chronic steroid doses of prednisone ≤10 mg/day or corticosteroid equivalent for ≥4 weeks are allowed. Other treatments for autoimmune diseases may be allowed upon medical monitor review.
• Hydroxyurea.
• Immunomodulatory drugs (for example, thalidomide, pomalidomide, or lenalidomide).
• Interferon.
• Thrombopoietin receptor agonists.
• Any investigational drug, including antihemojuvelin antibody. If the half-life of the investigational product is known, the exclusionary period prior to randomization is equal to 5 half-lives of the investigational product or 28 days, whichever is longer.
• Initiation of new iron chelation therapy or dose adjustments to existing iron chelation therapy ≤8 weeks prior to randomization. Participants on stable doses of iron chelation therapy for ≥8 weeks are allowed.
• Clinically significant anemia that is due to causes other than MF or Janus kinase (JAK) inhibitor therapy (for example, thalassemia, iron deficiency, vitamin B12 and/or folate deficiencies, autoimmune or hemolytic anemia, infections, or any active clinically significant bleeding or sequestration).
• Receipt of RBC transfusion for any reason(s) other than underlying MF within 12 weeks before randomization.
• Life expectancy <12 months per investigator's judgment.
• Clinically significant cardiovascular disease, defined as:

• New York Heart Association heart disease Class III or IV;
• Fridericia corrected QT interval >500 millisecond (ms) during screening;
• Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before screening.
• Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure of ≥160 millimetres of mercury (mmHg) and/or diastolic blood pressure ≥100 mmHg despite adequate treatment.
• 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 (including proximal and distal), pulmonary or arterial embolism, arterial thrombosis, or other venous thrombosis. Participants with prior superficial thrombophlebitis are allowed.
• Prior history of malignancies, other than MF. Participants who are free of other malignant disease for ≥2 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:

• Basal or squamous cell carcinoma of the skin;
• Carcinoma in situ of the cervix;
• Carcinoma in situ of the breast; and/or
• Incidental histologic finding of prostate cancer (T1a or T1b using the Tumour, Node, and Metastasis (TNM) staging system);
• Early papillary thyroid cancer (stage I \[T1-T2, N0, M0\]).
• History of solid organ or bone marrow transplantation.
• Active infection requiring intravenous antibiotics within 28 days or oral antibiotics within 7 days before randomization. Prophylactic antibiotics and/or antifungals for neutropenia are allowed.
• Known positivity for Human Immunodeficiency Virus (HIV), active hepatitis B virus (HBV), or active hepatitis C virus (HCV). Participants without known history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
• Body mass index ≥40 kilograms per square meter (kg/m\^2).
• Major surgery within 28 days before randomization.
• History of allergy/anaphylaxis to recombinant proteins, investigational product, or excipients (refer to the current elritercept investigator's brochure for a list of excipients), or ruxolitinib.
• Any of the following local laboratory abnormalities:

• Absolute neutrophil count <500/microliter (μL) (0.5×109/ liter (L)).
• Platelet count <50,000/μL (50×109/L) or >1,000,000/μL (1000×109/L).
• Blasts >5% as assessed in peripheral blood at screening or ≥10% in any historical bone marrow assessments. Participants with isolated transient elevations of peripheral blood blasts may be eligible after discussion between the investigator and medical monitor to confirm the blast count is not indicative of disease progression.
• Serum aspartate aminotransferase or alanine aminotransferase ≥3× the upper limit of normal (ULN).
• Total bilirubin ≥2×ULN. Participants with known history of Gilbert syndrome with unconjugated bilirubin less than (<) 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.
• Estimated glomerular filtration rate <30 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) as determined by the Chronic Kidney Disease Epidemiology Collaboration equation.
• Ferritin ≤50 micrograms per liter (μg/L).
• Folate ≤2.0 nanograms per milliliter (ng/mL).
• Vitamin B12 ≤200 picograms per milliliter (pg/mL).
• Ongoing participation in another interventional clinical trial.
• Participant is unwilling or, in the opinion of the investigator, the participant is unable to comply with the requirements of the protocol.
• Is a person of childbearing potential 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 elritercept or placebo.
• 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 treatment period until at least 60 days after the last dose of elritercept or placebo.
• 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 treatment period until at least 60 days after the last dose of elritercept or placebo.
• For participants in France: Persons under court protection, persons not affiliated with a social security system, and protected adults.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 29 centers

• Los Angeles Cancer Network — Glendale
• Cancer and Blood Specialty Clinic — Whittier
• MedStar Georgetown University Hospital — Washington D.C.
• Advanced Research, LLC — Coral Springs
• Bioresearch Partners — Miami
• AdventHealth - Cancer Institute - Orlando — Orlando
• Florida Clinical Trials Group — Tamarac
• Moffit Cancer Center — Tampa
• … and 21 more centers

Italy · 12 centers

Center list to be confirmed — check the primary protocol.

India · 10 centers

Center list to be confirmed — check the primary protocol.

France · 9 centers

• CHU de Nice — Nice
• Centre Hospitalier Lyon Sud — Pierre-Bénite
• CHU de Strasbourg — Strasbourg
• … and 6 more centers

Germany · 9 centers

Center list to be confirmed — check the primary protocol.

Brazil · 8 centers

• Centro de Ensino, Pesquisa e Inovacao do Hospital Sao Lucas (CEPIN HSL RJ / Rede Americas) — Rio de Janeiro
• Porto Alegre Clinical Hospital (HCPA) — Porto Alegre
• Hospital Mae De Deus - Integrated Oncology Center — Porto Alegre
• Hospital Sao Lucas da PUCRS — Porto Alegre
• Grupo Elora Pesquisa Clinica — Florianópolis
• Centro de Hematologia e Oncologia (CHO) — Joinville
• Hospital Amaral Carvalho (HAC) — Jaú
• Portuguese Charity of Sao Paulo — São Paulo

Japan · 8 centers

Center list to be confirmed — check the primary protocol.

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

South Korea · 7 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 7 centers

Center list to be confirmed — check the primary protocol.

Argentina · 6 centers

• Hospital Universitario Austral — Pilar
• Swiss Medical Center Barrio Parque — Buenos Aires
• Instituto Medico de la Fundacion Estudios Clinicos — Rosario
• Hospital Privado de Rosario — Rosario
• Hospital Aleman (HA) Deutsches Hospital — Buenos Aires
• BRCR Global — Córdoba

Greece · 6 centers

Center list to be confirmed — check the primary protocol.

Poland · 6 centers

Center list to be confirmed — check the primary protocol.

Belgium · 5 centers

• Centre Hospitalier Jolimont-Lobbes — La Louvière
• UZ Leuven — Leuven
• AZ Delta — Roeselare
• Ziekenhuis aan de Stroom-Cadix — Antwerp
• CHU Namur Site Mont Godinne — Yvoir

Chile · 5 centers

• Hospital Cliniico Regional de Concepcion Dr — Concepción
• IC La Serena Research — La Serena
• Icegclinic — Santiago
• Immunocel — Las Condes
• Centro de Oncologia de Precision — Santiago

Israel · 5 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

Australia · 4 centers

• Flinders Medical Centre — Bedford Park
• Mid North Coast Cancer Institute (MNCCI) — Coffs Harbour
• Tweed Valley Hospital — Cudgen
• South Eastern Sydney Local Health District — Kogarah

Austria · 4 centers

• Medizinische Universitat Wien (Medical University of Vienna - Austria) — Vienna
• Medizinische Universitat Innsbruck — Innsbruck
• Klinikum Wels-Grieskirchen — Wels
• Ordensklinikum Linz Elisabethinen — Linz

Bulgaria · 4 centers

• UMHAT 'Dr. Georgi Stranski', EAD — Pleven
• Dr. Pencho Georgiev - Outpatient Center — Plovdiv
• UMHAT Sv. Ivan Rilski — Sofia
• Specialized Hospital for Active Treatment of Haematological Diseases - Sofia — Sofia

Canada · 4 centers

• Juravinski Cancer Centre — Hamilton
• Princess Margaret Cancer Centre — Toronto
• Jewish General Hospital — Montreal
• McGill University Health Center — Montreal

Colombia · 4 centers

• Hospital Pablo Tobon Uribe — Medellín
• Clinica General del Norte De Barranquilla — Barranquilla
• Los Cobos Medical Center — Bogotá
• Funcacion santa Fe De Bogota — Bogota

Czechia · 4 centers

• Masaryk University Hospital Brno, Department of Internal Medicine, Hematology and Oncology — Brno
• Fakultni nemocnice Hradec Kralove — Hradec Králové
• Vseobecna fakultni nemocnice Praha — Prague
• Fakultni nemocnice Kralovske Vinohrady — Prague

Ireland · 4 centers

Center list to be confirmed — check the primary protocol.

Malaysia · 4 centers

Center list to be confirmed — check the primary protocol.

Romania · 4 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 4 centers

Center list to be confirmed — check the primary protocol.

Mexico · 3 centers

Center list to be confirmed — check the primary protocol.

Hungary · 2 centers

Center list to be confirmed — check the primary protocol.

Saudi Arabia · 2 centers

Center list to be confirmed — check the primary protocol.

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07623161 · TAK-226-3002 · 2026-525660-17-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗