Anemia in Patients with Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS). MedDRA version: 27.0 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10002272 Term: Anemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: elritercept
Product Code: PRD8997233
Pharmaceutical Form: Solution for injection
INN or Proposed INN: elritercept
CAS Number: 2727114-26-1
Current Sponsor code: KER-050
Other descriptive
Sponsors
Keros Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of MDS (Parts 1 and 2) according to WHO classification that meets International Prognostic Scoring System-Revised (IPSS-R) classification of very low, low, or intermediate risk disease. 2. or = 4 units of RBCs for hemoglobin =65 years) yes F.1.3.1 Number of subjects for this age range 76
Exclusion criteria
Exclusion criteria: 1. Active infection requiring parenteral antibiotic therapy within 28 days prior to C1D1 or oral antibiotics within 14 days of C1D1. Prophylactic antibiotics and/or antifungals for neutropenia are allowed. 2. Diagnosis of secondary MDS (ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases). 3. Vitamin B12 deficiency. 4. Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept. 5. Treatment with ESA within 56 days prior to C5D1. 6. Prior or concurrent chronic treatment with G-CSF or GM-CSF. 7. Iron chelation therapy if initiated within 8 weeks prior to Cycle 1 Day 1. 8. Vitamin B12 therapy within 8 weeks prior to Cycle 1 Day 1. 9. Treatment with another investigational drug or device or approved therapy for investigational use 450 x 10*9/L or < 30 x 10*9/L. 11. Transferrin saturation < 15%. 12. Ferritin < 50 µg/L. 13. Folate < 4.5 nmol/L (< 2.0 ng/mL). 14. Vitamin B12 < 148 pmol/L (< 200 pg/mL). 15. Estimated glomerular filtration rate (GFR) < 40 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]. 16. Pregnant or lactating females. Medical History •Diagnosis of MDS with deletion of chromosome 5q (Del5q). •Presence of uncontrolled heart disease or New York Heart Association Class III or IV heart failure. •Presence of uncontrolled hypertension (Grade = 2 high blood pressure). •History of stroke, deep venous thrombosis, or arterial embolism within 6 months prior to C1D1(or C5D1 for the Part 1 Extension). •Any malignancy other than MDS that has not been in remission and/or has required systemic therapy 1 year prior to C1D1 (or C5D1 for the Part 1 Extension). •Diagnosis of secondary MDS. •History of solid organ or hematological transplantation •Body mass index = 40 kg/m2. Treatment History •Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept. •Treatment with ESA within 8 weeks prior to C1D1 (or C5D1 for the Part 1 Extension). •Prior or concurrent chronic treatment with granulocyte colony stimulating factor (G-CSF) orgranulocyte-macrophage colony stimulating factor (GM-CSF), for reasons other than thetreatment of MDS.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: Dose Escalation • To evaluate the safety and tolerability of ascending doses of KER-050 in participants with very low, low, or intermediate risk MDS in order to determine the dose(s) that will be evaluated in Part 2 of the study. Part 2: Dose Confirmation • To confirm the safety and tolerability of the dose(s) selected in Part 1. Long-Term Extension •To evaluate the long-term safety and tolerability of KER-050 in participants with very low, low, or intermediate risk MDS in the Long Term Extension (LTE).;Secondary Objective: Secondary objectives (all parts) Safety Objective: •To evaluate the progression to higher risk MDS or acute myeloid leukemia (AML) Efficacy Objective: •To evaluate the efficacy of KER-050 on anemia in participants with very low, low, orintermediate risk MDS, separately for ring sideroblast (RS)-positive and non-RS populations Pharmacodynamic Objective: •To evaluate the pharmacodynamic (PD) effects of KER-050 on erythropoiesis in participants with very low, low, or intermediate risk MDS, separately for RS-positive and non-RS populations;Primary end point(s): Part 1 and Part 2: •Safety and tolerability as determined by the incidence of treatment emergent adverse events(TEAEs) and serious adverse events (SAEs). Long-term Extension: •Safety and tolerability as determined by the incidence of TEAEs and SAEs over time;Timepoint(s) of evaluation of this end point: 105 Weeks unless participants elect to continue in the Long-term Extension (LTE) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Incidence of progression to higher risk MDS or AML per World Health Organization (WHO) 2016 criteria. 2. Proportion of low transfusion burden (LTB) and high transfusion burden (HTB) participants who achieve red blood cell (RBC) transfusion independence (TI) = 8 weeks, overall and by RS status. 3. Proportion of participants who achieve modified 2006 International Working Group (IWG) Hematologic Improvement-Erythroid (HI E) response overall and by RS status, where: - In LTB participants and participants with non-transfused anemia, response is defined as a mean hemoglobin (Hgb) increase of = 1.5 g/dL from Baseline during any 8 week period during the treatment period. - In HTB participants, response is defined as a reduction by = 4 units of RBCs transfused during any 8-week period on study compared with the 8-week period prior to study Cycle 1 Day 1 (C1D1). 4. Proportion of participants who achieve overall erythroid response, defined as either HI-E or TI over any 8-week period, overall and by RS status. 5. Proportion of participants who achieve erythropoietic improvement overall and by RS status, where: - In low-transfusion burden (LTB) participants and participants with non-transfused anemia, improvement is defined as a mean hemoglobin (Hgb) increase of = 1.5 g/dL from Baseline for = 14 days (in the absence of red blood cell [RBC] transfusions). - In high transfusion burden (HTB) participants, improvement is defined as a reduction of = 50% or = 4 RBC units transfused compared to pretreatment over an 8-week period. 6. Mean change from baseline in hemoglobin [Time Frame: Measured over the course of study, up to approximately 25 weeks from study day 1 unless participants elect to continue on in the LTE]. 7. Time to HI-E response [Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks unless participants elect to continue on in the LTE)]. 8. Duration of HI-E response [Time Frame: From treatment initiation to End of St | — |
Countries
Australia, Czechia, Czech Republic, France, Germany, Israel, New Zealand, Spain, United States
Contacts
Public ContactCentral Contact Person
Keros Therapeutics, Inc.
Outcome results
None listed