Recruiting
Phase 3
A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib
Condition(s) studied
MyelofibrosisAnemia
Investigational drug(s) / intervention(s)
PlaceboElritercept
Placebo: Elritercept-matching placebo
Elritercept: Elritercept, SC, injection
Study summary
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.
Eligibility
Inclusion Criteria:
1. Aged ≥18 years at the time of signing the informed consent form (ICF).
2. Able to understand the purpose and risks of the trial and voluntarily sign an ICF.
3. 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.
4. Transfusion status as assessed in the 12 weeks immediately preceding randomization classified as Transfusion Dependent: 3 to 8 RBC units over 12 weeks.
5. 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.
6. Eastern Cooperative Oncology Group score less than or equal to (≤) 2.
Exclusion Criteria:
1. Prior treatment with luspatercept, sotatercept, or other transforming growth factor beta inhibitors or activin receptor ligand traps.
2. Systemic treatment within 28 days before randomization with any of the following:
1. Androgens (including danazol). Participants on stable androgen dosing for hypogonadism for ≥8 weeks are allowed.
2. erythropoiesis-stimulating agents.
3. granulocyte colony stimulating factor or granulocyte-macrophage colony stimulating factor.
4. 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.
5. Hydroxyurea.
6. Immunomodulatory drugs (for example, thalidomide, pomalidomide, or lenalidomide).
7. Interferon.
8. Thrombopoietin receptor agonists.
9. 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.
3. 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.
4. 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).
5. Receipt of RBC transfusion for any reason(s) other than underlying MF within 12 weeks before randomization.
6. Life expectancy \<12 months per investigator's judgment.
7. Clinically significant cardiovascular disease, defined as:
1. New York Heart Association heart disease Class III or IV;
2. Fridericia corrected QT interval \>500 millisecond (ms) during screening;
3. Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before screening.
8. 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.
9. 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.
10. 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:
1. Basal or squamous cell carcinoma of the skin;
2. Carcinoma in situ of the cervix;
3. Carcinoma in situ of the breast; and/or
4. Incidental histologic finding of prostate cancer (T1a or T1b using the Tumour, Node, and Metastasis (TNM) staging system);
5. Early papillary thyroid cancer (stage I \[T1-T2, N0, M0\]).
11. History of solid organ or bone marrow transplantation.
12. 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.
13. 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.
14. Body mass index ≥40 kilograms per square meter (kg/m\^2).
15. Major surgery within 28 days before randomization.
16. 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.
17. Any of the following local laboratory abnormalities:
1. Absolute neutrophil count \<500/microliter (μL) (0.5×109/ liter (L)).
2. Platelet count \<50,000/μL (50×109/L) or \>1,000,000/μL (1000×109/L).
3. 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.
4. Serum aspartate aminotransferase or alanine aminotransferase ≥3× the upper limit of normal (ULN).
5. 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.
6. 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.
7. Ferritin ≤50 micrograms per liter (μg/L).
8. Folate ≤2.0 nanograms per milliliter (ng/mL).
9. Vitamin B12 ≤200 picograms per milliliter (pg/mL).
18. Ongoing participation in another interventional clinical trial.
19. Participant is unwilling or, in the opinion of the investigator, the participant is unable to comply with the requirements of the protocol.
20. 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.
21. 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.
22. 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.
23. For participants in France: Persons under court protection, persons not affiliated with a social security system, and protected adults.
Primary outcome measure(s)
- 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 — From Cycle 1 Day 1 through Week 36 (each cycle is 28 days)
RBC-TI is defined as no RBC transfusions administered for the specified time period during study treatment.
Trial sites (195)
| Facility | City | Region | Status |
| Banner MD Anderson Cancer Center |
Gilbert |
Arizona |
Not Yet Recruiting |
| Los Angeles Cancer Network |
Glendale |
California |
Not Yet Recruiting |
| Cancer and Blood Specialty Clinic |
Whittier |
California |
Not Yet Recruiting |
| MedStar Georgetown University Hospital |
Washington D.C. |
District of Columbia |
Not Yet Recruiting |
| Advanced Research, LLC |
Coral Springs |
Florida |
Recruiting |
| Bioresearch Partners |
Miami |
Florida |
Not Yet Recruiting |
| AdventHealth - Cancer Institute - Orlando |
Orlando |
Florida |
Not Yet Recruiting |
| Florida Clinical Trials Group |
Tamarac |
Florida |
Not Yet Recruiting |
| Moffit Cancer Center |
Tampa |
Florida |
Not Yet Recruiting |
| Emory University |
Atlanta |
Georgia |
Not Yet Recruiting |
| Tufts Medical Center |
Boston |
Massachusetts |
Not Yet Recruiting |
| Washington University School of Medicine |
St Louis |
Missouri |
Not Yet Recruiting |
| St. Vincent Regional Hospital Cancer Centers |
Billings |
Montana |
Not Yet Recruiting |
| University of New Mexico Comprehensive Cancer Center |
Albuquerque |
New Mexico |
Not Yet Recruiting |
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
Not Yet Recruiting |
| Icahn School of Medicine at Mount Sinai |
New York |
New York |
Not Yet Recruiting |
| Duke Blood Cancer Center |
Durham |
North Carolina |
Not Yet Recruiting |
| Novant Health |
Winston-Salem |
North Carolina |
Not Yet Recruiting |
| Cleveland Clinic |
Cleveland |
Ohio |
Not Yet Recruiting |
| Oregon Health and Science University |
Portland |
Oregon |
Not Yet Recruiting |
| Thomas Jefferson University |
Philadelphia |
Pennsylvania |
Not Yet Recruiting |
| University of Pittsburgh Medical Center |
Pittsburgh |
Pennsylvania |
Not Yet Recruiting |
| Allegheny Health Network Cancer Institute - West Penn Hospital Location |
Pittsburgh |
Pennsylvania |
Not Yet Recruiting |
| Medical University of South Carolina |
Charleston |
South Carolina |
Not Yet Recruiting |
| Vanderbilt-Ingram Cancer Center (VICC)-Nashville |
Nashville |
Tennessee |
Not Yet Recruiting |
| Baylor University Medical Center |
Dallas |
Texas |
Not Yet Recruiting |
| MD Anderson Cancer Center |
Houston |
Texas |
Not Yet Recruiting |
| The University of Utah-Huntsman Cancer Institute |
Houston |
Texas |
Not Yet Recruiting |
| LUMI Research |
Houston |
Texas |
Recruiting |
| University of Washington |
Seattle |
Washington |
Not Yet Recruiting |
| Hospital Universitario Austral |
Pilar |
Buenos Aires |
Not Yet Recruiting |
| Swiss Medical Center Barrio Parque |
Buenos Aires |
Ciudad Autonoma de BuenosAires |
Not Yet Recruiting |
| Instituto Medico de la Fundacion Estudios Clinicos |
Rosario |
Santa Fe Province |
Not Yet Recruiting |
| Hospital Privado de Rosario |
Rosario |
Santa Fe Province |
Not Yet Recruiting |
| Hospital Aleman (HA) Deutsches Hospital |
Buenos Aires |
Argentina |
Not Yet Recruiting |
| BRCR Global |
Córdoba |
Argentina |
Not Yet Recruiting |
| Flinders Medical Centre |
Bedford Park |
Adelaide, SA |
Not Yet Recruiting |
| Mid North Coast Cancer Institute (MNCCI) |
Coffs Harbour |
New South Wales |
Not Yet Recruiting |
| Tweed Valley Hospital |
Cudgen |
New South Wales |
Not Yet Recruiting |
| South Eastern Sydney Local Health District |
Kogarah |
New South Wales |
Not Yet Recruiting |
+ 155 more sites — see the full list on the official registry below.