Health Condition 1: D464- Refractory anemia, unspecified
Conditions
Interventions
Intervention1: Elritercept, 100mg per ml solution for injection: Dose: Liquid solution for subcutaneous (SC) injection
Frequency:13 doses per year
Route of administration: subcutaneous (SC) injection
Sponsors
Takeda Development Center Americas Inc
IQVIA RDS INDIA PRIVATELIMITED
Eligibility
Inclusion criteria
Inclusion criteria: 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. Male or female greater than or equal to 18 years of age at the time of signing informed consent. 3. Diagnosis of MDS with or without RS according to WHO 2016 classification that meets the IPSS-R classification of very low-, low-, or intermediate-risk MDS. 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 b. HTB, defined as greater than or equal to 8 RBC units per 16 weeks c. For all participants i. Only transfusion events for a pretransfusion Hgb less than 10 g per dL are counted toward eligibility ii. At least 1 transfusion event in each 8-week period and a minimum of 2 transfusion events separated by greater than or equal to 7 days within the 16-week period immediately preceding randomization iii. No consecutive 56-day period can be RBC transfusion-free during the 16-week period immediately preceding randomization. 5. Refractory or intolerant to prior ESA treatment (discontinued greater than or equal to 4 weeks before randomization), or unlikely to respond to ESA treatment, defined as follows a. Refractory to prior ESA treatment documentation of nonresponse or a response that was no longer maintained with a prior ESA-containing regimen, either as a single agent or combination (e.g., with granulocyte colony-stimulating factor (G CSF)) ESA regimen must have been either i. Recombinant human EPO greater than or equal to 40,000 IU per week for greater than or equal to 8 doses or equivalent ii. Darbepoetin alpha greater than or equal to 500 mcg every 3 weeks for greater than or equal to 4 doses or equivalent. b. Intolerant to prior ESA treatment documentation of discontinuation of a prior ESA-containing regimen, either as a single agent or combination (e.g., with G-CSF), at any time after introduction due to intolerance or an AE. c. Unlikely to respond to ESA treatment low chance of response to ESA based on an endogenous serum EPO level greater than 200 U per L. 6. Less than 5 percent blasts in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader. 7. ECOG performance status of 0 to 2 8. Females of childbearing potential and sexually active males must agree to use adequate contraception methods 9. In the opinion of the Investigator, the participant is able and willing to comply with the requirements of the protocol (e.g., all study procedures, return for follow-up visits).
Exclusion criteria
Exclusion criteria: 1. Del(5q) MDS or therapy-related (secondary) MDS. 2. Anemia due to any other known cause (e.g., thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate). 3. Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks before randomization. 4. Clinically significant cardiovascular disease defined as a. New York Heart Association heart disease class III or IV b. Fridericia corrected QT (QTcF) interval greater than 500 milliseconds during Screening c. Presence of uncontrolled hypertension defined as mean systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 100 mm Hg during Screening d. Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before Screening. 5. Known ejection fraction less than 35 percent, confirmed by a local echocardiogram performed during Screening, or a previously performed echocardiogram if collected within 6 months before Screening. 6. Child-Pugh class C hepatic impairment. 7. Stroke, deep vein thrombosis, or pulmonary embolism within 6 months before Screening. 8. Any known history of AML. 9. Prior history of malignancies, other than MDS, unless the participant has been free of the disease (including completion of any treatment, including maintenance, for prior malignancy) for greater than or equal 5 years. However, 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 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 treatment (e.g. antibiotics, antifungals, or antivirals) within 28 days, or oral treatment within 14 days before randomization. 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. 13. Body mass index greater than or equal 40 kg per m2. 14. Major surgery within 28 days before randomization. 15. History of allergy or anaphylaxis to investigational medicinal product (IMP) excipients (refer to the current elritercept IB for a list of excipients) or recombinant proteins. Treatment History 16. Prior use of elritercept, luspatercept, or sotatercept. 17. Prior use of hypomethylating agents (HMAs), isocitrate dehydrogenase inhibitor, lenalidomide, imetelstat, or immunosuppressive therapy given for treatment of MDS. 18. Iron chelation therapy initiated within 8 weeks before randomization. Participants on stable doses of iron chelation therapy for greater than or equal 8 weeks are allowed. 19. Vitamin B12 or folate therapy initiated within 4 weeks before randomization. Participants on stable replacement doses for greater than or equal 4 weeks and without ongoing concurrent vitamin B12 or folate deficiency are allowed. 20. Androgen use within 8 weeks before randomization. Participants on
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of elritercept in reducing red blood cell (RBC) transfusions EndpointsTimepoint: To evaluate the efficacy of elritercept in reducing red blood cell (RBC) transfusions Endpoints | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of elritercept in reducing RBC transfusions over longer intervals & or in participants with high-transfusion burden (HTB) To assess the safety & tolerability of elritercepTimepoint: Proportion of participants achieving TI for greater than or equal to 24 weeks from baseline through week 48 Proportion of participants with HTB achieving TI for greater than or equal to 8 weeks from baseline through week 24 Incidence of treatment-emergent adverse events & serious adverse events Change from baseline in clinical laboratory values, vital signs, & electrocardiograms | — |
Countries
Australia, Brazil, Bulgaria, Canada, Chile, Czech Republic, France, Germany, Hungary, India, Ireland, Israel, Italy, Lithuania, Peru, Poland, Republic of Korea, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States of America
Contacts
Public ContactShweta Pradhan
IQVIA RDS (India) Private Limited
Outcome results
None listed