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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: KER-050 monotherapy; Drug: KER-050 in combination with ruxolitinib

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 Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rachael Ryzman; Phone Number: 603-548-3907; Email: KER050-MF-301@kerostx.com

Study Locations

• Australia
  • New South Wales
    • Tweed Heads, New South Wales, Australia, 2485
      • Recruiting
      • The Tweed Hospital
  • South Australia
    • Woodville South, South Australia, Australia, 5042
      • Recruiting
      • Flinders Medical Centre
  • Victoria
    • Fitzroy, Victoria, Australia, 3355
      • Recruiting
      • St. Vincent's Hospital Melbourne
    • Melbourne, Victoria, Australia, 3050
      • Recruiting
      • Royal Melbourne Hospital
    • Wendouree, Victoria, Australia, 3355
      • Recruiting
      • Ballarat Oncology & Hematology Service

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm 1a; Dose Escalation KER-050 (SC, solution for injection, every 4 weeks) monotherapy	Drug: KER-050 monotherapy; KER-050 administered (SC) for up to 13 cycles
EXPERIMENTAL: Arm 1b; 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; KER-050 administered (SC) for up to 13 cycles in combination with standard of care ruxolitinib
EXPERIMENTAL: Arm 2a; Dose Expansion KER-050 (SC, solution for injection, every 4 weeks) monotherapy	Drug: KER-050 monotherapy; KER-050 administered (SC) for up to 13 cycles
EXPERIMENTAL: Arm 2b; 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; KER-050 administered (SC) for up to 13 cycles in combination with standard of care ruxolitinib

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Keros Therapeutics, Inc.
• Collaborators: IQVIA Biotech

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 16, 2021
• Primary Completion (ANTICIPATED): April 1, 2025
• Study Completion (ANTICIPATED): June 1, 2025

Study Registration Dates

• First Submitted: August 23, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (ACTUAL): September 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 17, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Anemia; Bone marrow; Thrombocytopenia; Red blood cells
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: KER050-MF-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No