A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elritercept (KER-050) for the Treatment of Transfusion-Dependent Anemia in Adult Participants with Very Low-, Low-, or Intermediate-Risk Myelodysplastic Syndromes (MDS) (RENEW)
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Anemias Carenciales, Síndromes mielodisplásicos, Linfoma
CENTRO INVESTIGADOR
H. Fundación Jiménez Díaz
INVESTIGADOR PRINCIPAL
Teresa Arquero Portero
CENTRO INVESTIGADOR
H.U. Ramón y Cajal
INVESTIGADOR PRINCIPAL
Kyra Velázquez Kennedy
FECHA DE APERTURA
Marzo, 2025
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
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 18 years of age at the time of signing informed consent.
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. 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. Refractory or intolerant to prior ESA treatment (discontinued 4 weeks before randomization), or unlikely to respond to ESA treatment
6. Less than 5% blasts in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader
7. Eastern Cooperative Oncology Group performance status of 0 to 2
8. Females of childbearing potential and sexually active males must agree to use adequate methods
2. Male or female 18 years of age at the time of signing informed consent.
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. 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. Refractory or intolerant to prior ESA treatment (discontinued 4 weeks before randomization), or unlikely to respond to ESA treatment
6. Less than 5% blasts in an evaluable bone marrow aspirate collected at Screening, read by an independent central reader
7. Eastern Cooperative Oncology Group performance status of 0 to 2
8. Females of childbearing potential and sexually active males must agree to use adequate methods
CRITERIOS DE EXCLUSIÓN
1. Del(5q) MDS or therapy-related (secondary) MDS
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 40 kg/m2
14. Major surgery within 28 days before randomization
16. Prior use of elritercept, luspatercept, sotatercept.
17. Prior use of hypomethylating agents (HMA), isocitrate dehydrogenase inhibitor, lenalidomide, imetelstat, or immune-suppressive 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 8 weeks are allowed
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
24. Serum EPO level 500 U/L
25. Platelet count 450 × 109/L or 25 × 109/L
2. Anemia due to any other known cause (e.g., thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate).
26. Absolute neutrophil count 500/L
27. Serum aspartate aminotransferase or alanine aminotransferase 3 × the upper limit of normal
28. Total bilirubin 2 × ULN unless attributable to Gilbert's syndrome
29. Ferritin 50 g/L
30. Folate 2.0 ng/mL
31. Vitamin B12 200 pg/mL
32. Estimated glomerular filtration rate < 30 mL/min/1.73m2 as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
33. Pregnant or lactating female
3. Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks before randomization.
4. Clinically significant cardiovascular disease
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. 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 participant has been free of the disease (including completion of any treatment, including maintenance, for prior malignancy) for 5 years.
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 40 kg/m2
14. Major surgery within 28 days before randomization
16. Prior use of elritercept, luspatercept, sotatercept.
17. Prior use of hypomethylating agents (HMA), isocitrate dehydrogenase inhibitor, lenalidomide, imetelstat, or immune-suppressive 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 8 weeks are allowed
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
24. Serum EPO level 500 U/L
25. Platelet count 450 × 109/L or 25 × 109/L
2. Anemia due to any other known cause (e.g., thalassemia, hemolytic anemia, bleeding events, or deficiency of iron, B12, and/or folate).
26. Absolute neutrophil count 500/L
27. Serum aspartate aminotransferase or alanine aminotransferase 3 × the upper limit of normal
28. Total bilirubin 2 × ULN unless attributable to Gilbert's syndrome
29. Ferritin 50 g/L
30. Folate 2.0 ng/mL
31. Vitamin B12 200 pg/mL
32. Estimated glomerular filtration rate < 30 mL/min/1.73m2 as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
33. Pregnant or lactating female
3. Receipt of RBC transfusion for any reason(s) other than underlying MDS within 16 weeks before randomization.
4. Clinically significant cardiovascular disease
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. 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 participant has been free of the disease (including completion of any treatment, including maintenance, for prior malignancy) for 5 years.
DESCRIPCIÓN
To evaluate the efficacy of elritercept in reducing red blood cell (RBC) transfusions
PALABRAS CLAVE
anemia, mds, myelodysplastic syndrome
