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

Phase 2

Recruiting

• Conditions: Myelofibrosis
• Interventions: Drug: KER-050 in combination with ruxolitinib; Drug: KER-050 monotherapy

• Registration Number: NCT05037760
• Lead Sponsor: Keros Therapeutics, Inc.

Brief Summary

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

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)

Study Timeline

• Status Verified: 2021-08
• Study First Submitted: 2021-08-23
• Study First Submitted QC: 2021-09-01
• Study First Posted: 2021-09-08
• Study Start: 2021-12-16
• Last Update Submitted: 2022-03-02
• Last Update Posted: 2022-03-17
• Primary Completion: 2025-04
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 110

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

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Exclusion Criteria

• Presence of the following cardiac conditions:

  1. New York Heart Association Class 3 or 4 heart failure
  2. QTcF >500 msec on the screening or C1D1 electrocardiogram (ECG)
  3. Uncontrolled clinically significant arrhythmia (participants with rate-controlled atrial fibrillation are not excluded)
  4. 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:

  1. Erythropoiesis stimulating agent (ESA)
  2. Granulocyte colony-stimulating factor (G-CSF)
  3. Granulocyte-macrophage colony-stimulating factor (GM-CSF)
  4. Thrombopoietin agonists (TPO)
  5. Immunomodulator imide drugs (IMiDs; e.g., thalidomide, pomalidomide, lenalidomide)
  6. Interferon

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Arm 1b	KER-050 in combination with ruxolitinib	Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily)
Arm 1a	KER-050 monotherapy	Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) monotherapy
Arm 2a	KER-050 monotherapy	Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) monotherapy
Arm 2b	KER-050 in combination with ruxolitinib	Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) in combination with standard of care ruxolitinib (oral, tablet, twice daily)

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (Safety and Tolerability)	64 Weeks	Safety and tolerability as determined by the incidence of adverse events (AEs), including severe AEs and serious AEs (SAEs)

Secondary Outcome Measures

Name	Time	Method
Subgroup of participants with anemia requiring red blood cell (RBC) transfusions	24 weeks	* 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
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 accelerated MF (bone marrow blasts ≥10%)	At Week 24 and at Week 52
Subgroup of transfusion-independent participants	24 weeks	* 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
Proportion of participants with progression to AML (bone marrow blasts >20%)	At Week 24 and at Week 52

Trial Locations

Locations (5)

The Tweed Hospital; 🇦🇺 Tweed Heads, New South Wales, Australia

Flinders Medical Centre; 🇦🇺 Woodville South, South Australia, Australia

Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

Ballarat Oncology & Hematology Service; 🇦🇺 Wendouree, Victoria, Australia

St. Vincent's Hospital Melbourne; 🇦🇺 Fitzroy, Victoria, Australia