Study to Evaluate KER-050 as a Monotherapy or in Combination With Ruxolitinib in Myelofibrosis

Study Overview
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Brief Summary
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This is a Phase 2, multicenter, open-label study to evaluate the safety and efficacy of KER-050 as monotherapy or in combination with ruxolitinib in participants with Myelofibrosis.

Detailed Description
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KER-050 is an investigational 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 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of KER-050 as Monotherapy or in Combination With Ruxolitinib in Participants With Myelofibrosis

Conditions
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Myelofibrosis

Intervention / Treatment
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* Drug: KER-050 monotherapy
* Drug: KER-050 in combination with ruxolitinib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female ≥18 years of age, at the time of signing informed consent. Diagnosis of PMF, post-PV MF, or post-ET MF according to the 2017 World Health Organization criteria. Arm-specific criteria: Arm 1A: Previously treated with JAK inhibitor(s) or Participant is ineligible for JAK inhibitor(s) Anemia, defined as hemoglobin ≤10 g/dL during screening, or receiving RBC transfusions Arm 2A: Previously treated with JAK inhibitor(s) or Participant is ineligible for JAK inhibitor(s) Anemia, defined as hemoglobin ≤10 g/dL during screening, or receiving RBC transfusions Arm-specific criteria for 1B and 2B: Has been receiving ruxolitinib for ≥8 weeks prior to C1D1 and on a stable dose for ≥4 weeks prior to C1D1. Anemia, defined as hemoglobin ≤10 g/dL during screening, or receiving RBC transfusions Key Exclusion Criteria: Presence of the following cardiac conditions: New York Heart Association Class 3 or 4 heart failure QTcF >500 msec on the screening or C1D1 electrocardiogram (ECG) Uncontrolled clinically significant arrhythmia (participants with rate-controlled atrial fibrillation are not excluded) Acute myocardial infarction or unstable angina pectoris <6 months prior to C1D1 History of stroke, deep venous thrombosis, or arterial embolism within 6 months prior to C1D1. Any malignancy other than PMF, post-ET MF, or post-PV MF that has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy, or surgery, within 1 year prior to C1D1. In-situ cancers, squamous cell, and basal cell carcinomas which have been fully excised, and monoclonal gammopathy of unclear significance are allowed at the discretion of the Investigator. History of solid organ or hematological transplantation. Presence of uncontrolled hypertension, defined as systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg despite adequate treatment. Diagnosis of hemolytic anemia, active bleeding, hemoglobinopathies, or congenital disorders as a cause of the participant's anemia. CTCAE Grade ≥2 bleeding events within the 3 months prior to C1D1. Bone marrow blast percentage >2%. Participants with blast % between 2-5% are allowed if at least 2 bone marrows >6 months apart demonstrate stability of blast percentage, these participants must be reviewed with the Medical Monitor prior to study entry. Prior treatment with luspatercept, sotatercept, or other commercially available or investigational TGF-β inhibitors (all Arms) Treatment within 28 days prior to C1D1 with: Erythropoiesis stimulating agent (ESA) Granulocyte colony-stimulating factor (G-CSF) Granulocyte-macrophage colony-stimulating factor (GM-CSF) Thrombopoietin agonists (TPO) Immunomodulator imide drugs (IMiDs; e.g., thalidomide, pomalidomide, lenalidomide) Interferon

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1a<br>Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) monotherapy | Drug: KER-050 monotherapy<br>* KER-050 administered (SC) for up to 13 cycles<br>|
| Experimental: Arm 1b<br>Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily) | Drug: KER-050 in combination with ruxolitinib<br>* KER-050 administered (SC) for up to 13 cycles in combination with standard of care ruxolitinib<br>|
| Experimental: Arm 2a<br>Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) monotherapy | Drug: KER-050 monotherapy<br>* KER-050 administered (SC) for up to 13 cycles<br>|
| Experimental: Arm 2b<br>Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily) | Drug: KER-050 in combination with ruxolitinib<br>* KER-050 administered (SC) for up to 13 cycles in combination with standard of care ruxolitinib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (Safety and Tolerability) | Safety and tolerability as determined by the incidence of adverse events (AEs), including severe AEs and serious AEs (SAEs) | 64 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subgroup of transfusion-independent participants | Proportion of participants with mean hemoglobin increase ≥1.5 g/dL from baseline over a period of >12 consecutive weeks Proportion of participants with mean hemoglobin increase ≥2.0 g/dL from baseline over a period of >12 consecutive weeks Proportion of participants with a decrease of ≥1 in Brief Fatigue Inventory (BFI) score from baseline | 24 weeks | 
| Subgroup of participants with anemia requiring red blood cell (RBC) transfusions | Proportion of participants with RBC transfusion independence over a period of >12 consecutive weeks Proportion of participants with decrease in number of RBC transfusions from baseline over a period of >12 consecutive weeks | 24 weeks | 
| Proportion of participants with decrease in spleen volume of ≥35% from baseline as measured by computed tomography (CT) (excluding participants status post splenectomy or splenic irradiation) |  | At Week 24 and at Week 52 | 
| Proportion of participants with improvement in the Myelofibrosis Symptom Assessment Form Total Symptom Score (MF-SAF-TSS) of ≥50% from baseline |  | At Week 24 and at Week 52 | 
| Proportion of participants with progression to AML (bone marrow blasts >20%) |  | At Week 24 and at Week 52 | 
| Proportion of participants with progression to accelerated MF (bone marrow blasts ≥10%) |  | At Week 24 and at Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thrombocytopenia, Anemia, Red blood cells, Bone marrow