A Study of KER-050 to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of KER-050 on anemia in patients with very low, low or intermediate risk MDS.

Detailed Description
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KER-050 is a therapeutic protein designed to increase red blood cell and platelet production by inhibiting the signaling of a subset of the transforming growth factor beta (TGF-ß) family of proteins to promote hematopoiesis. It is being developed for the treatment of low blood cell counts, or cytopenias including anemia and thrombocytopenia in patients with Myelodysplastic Syndrome (MDS) and Myelofibrosis (MF).

Official Title
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A Phase 2, Open-Label, Ascending Dose Study of KER-050 for the Treatment of Anemia in Patients With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS)

Conditions
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Myelodysplastic Syndromes, Cytopenia

Intervention / Treatment
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* Drug: KER-050


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of MDS according to World Health Organization (WHO)/French American British (FAB) classification that meets Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease. < 5% blasts in bone marrow. Peripheral blood white blood cell count <13,000/µL. Anemia defined as: In non-transfused participants, having received no red blood cell (RBC) transfusions within 8 weeks Hgb concentration ≤ 10.0 g/dL OR In LTB participants, having received 1 to 3 units RBCs for Hgb ≤ 9.0 g/dL within 8 weeks OR In HTB participants, having received ≥ 4 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia. Females of child-bearing potential and sexually active males must agree to use effective methods of contraception. Key Exclusion Criteria: Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1. Diagnosis of secondary MDS (i.e., MDS known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases). Vitamin B12 deficiency. Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept. Treatment within 28 days prior to Cycle 1 Day 1 with: Erythropoiesis stimulating agent (ESA) OR Granulocyte colony-stimulating factor (G-CSF) OR Granulocyte-macrophage colony-stimulating factor (GM-CSF) Iron chelation therapy if initiated within 8 weeks prior to Cycle 1 Day 1. Vitamin B12 therapy within 8 weeks prior to Cycle 1 Day 1. Treatment with another investigational drug or device or approved therapy for investigational use < or = 28 days prior to Cycle 1 Day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer. Platelet count > 450 x 10*9/L or < 30 x 10*9/L. Transferrin saturation < 15%. Ferritin < 50 µg/L. Folate < 4.5 nmol/L (< 2.0 ng/mL). Vitamin B12 < 148 pmol/L (< 200 pg/mL). Estimated glomerular filtration rate (GFR) < 40 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]. Pregnant or lactating females

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Ascending dose study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KER-050 Cohort 1<br>Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 4 cycles. Participants have the option to continue to receive KER-050 once 4 cycles have been completed for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles. | Drug: KER-050<br>* KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles in a Long-Term Extension.<br>|
| Experimental: KER-050 Cohort 2<br>Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 4 cycles. Participants have the option to continue to receive KER-050 once 4 cycles have been completed for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles. | Drug: KER-050<br>* KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles in a Long-Term Extension.<br>|
| Experimental: KER-050 Cohort 3<br>Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles. | Drug: KER-050<br>* KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles in a Long-Term Extension.<br>|
| Experimental: KER-050 Cohort 4<br>Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles. | Drug: KER-050<br>* KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles in a Long-Term Extension.<br>|
| Experimental: KER-050 Cohort 5<br>Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles. | Drug: KER-050<br>* KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles in a Long-Term Extension.<br>|
| Experimental: KER-050 Dose Confirmation Cohort<br>Participants to receive KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles. | Drug: KER-050<br>* KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles in a Long-Term Extension.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) and serious adverse events (SAEs). | Type, frequency, severity of AEs and relationship of AEs to KER-050 | From treatment initiation to end of study, approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentrations of KER-050 | Pharmacokinetics of KER-050 | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Erythroid response in low-transfusion burden (LTB) and high-transfusion burden (HTB) participants. | In LTB participants, the proportion of participants who have a hemoglobin increase of ≥ 1.5 g/dL from Baseline for ≥ 14 days (in the absence of RBC transfusions). In HTB participants, the proportion of participants having a reduction of ≥ 50% or ≥ 4 RBC units transfused compared to pretreatment over an 8-week period. | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria | Change in baseline laboratory assessments prior to treatment with KER-050 and after treatment with KER-050 | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria | Change in baseline bone marrow assessments prior to treatment with KER-050 and after treatment with KER-050 | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Modified 2006 International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response | In LTB participants, the proportion of participants with an increase of ≥ 1.5 g/dL from pretreatment hemoglobin during any 8-week period on study compared to Baseline. In HTB participants, the proportion of participants having a reduction by ≥ 4 units of RBCs transfused (for a hemoglobin ≤ 9.0 g/dL) during any 8-week period on study, compared with the 8-week period prior to study Cycle 1 Day 1. | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Mean change from baseline in hemoglobin | Change in baseline hemoglobin prior to treatment with KER-050 and after treatment with KER-050 | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Time to erythroid response and modified 2006 IWG HI-E response | Time to erythroid response prior to treatment with KER-050 and after treatment with KER-050 | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Duration of erythroid response and modified 2006 IWG HI-E response | Duration of erythroid response prior to treatment with KER-050 and after treatment with KER-050 | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Frequency of red blood cell (RBC) transfusions and rate of RBC transfusion independence ≥ 8 weeks | Frequency and rate of RBC transfusions prior to treatment with KER-050 and after treatment with KER-050 | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 
| Change from Baseline in RBC counts and reticulocytes | Change in baseline RBC counts and reticulocytes prior to treatment with KER-050 and after treatment with KER-050 | Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transfusion