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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05037760
Recruitment Status : Recruiting
First Posted : September 8, 2021
Last Update Posted : March 17, 2022
Sponsor:
Collaborator:
IQVIA Biotech
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Myelofibrosis Drug: KER-050 monotherapy Drug: KER-050 in combination with ruxolitinib Phase 2

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 16, 2021
Estimated Primary Completion Date : April 2025
Estimated Study Completion Date : June 2025


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




Primary Outcome Measures :
  1. Incidence of adverse events (Safety and Tolerability) [ Time Frame: 64 Weeks ]
    Safety and tolerability as determined by the incidence of adverse events (AEs), including severe AEs and serious AEs (SAEs)


Secondary Outcome Measures :
  1. Subgroup of transfusion-independent participants [ Time Frame: 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

  2. Subgroup of participants with anemia requiring red blood cell (RBC) transfusions [ Time Frame: 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

  3. 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) [ Time Frame: At Week 24 and at Week 52 ]
  4. Proportion of participants with improvement in the Myelofibrosis Symptom Assessment Form Total Symptom Score (MF-SAF-TSS) of ≥50% from baseline [ Time Frame: At Week 24 and at Week 52 ]
  5. Proportion of participants with progression to AML (bone marrow blasts >20%) [ Time Frame: At Week 24 and at Week 52 ]
  6. Proportion of participants with progression to accelerated MF (bone marrow blasts ≥10%) [ Time Frame: At Week 24 and at Week 52 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05037760


Contacts
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Contact: Rachael Ryzman 603-548-3907 KER050-MF-301@kerostx.com

Locations
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Australia, New South Wales
The Tweed Hospital Recruiting
Tweed Heads, New South Wales, Australia, 2485
Australia, South Australia
Flinders Medical Centre Recruiting
Woodville South, South Australia, Australia, 5042
Australia, Victoria
St. Vincent's Hospital Melbourne Recruiting
Fitzroy, Victoria, Australia, 3355
Royal Melbourne Hospital Recruiting
Melbourne, Victoria, Australia, 3050
Ballarat Oncology & Hematology Service Recruiting
Wendouree, Victoria, Australia, 3355
Sponsors and Collaborators
Keros Therapeutics, Inc.
IQVIA Biotech
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Responsible Party: Keros Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05037760    
Other Study ID Numbers: KER050-MF-301
First Posted: September 8, 2021    Key Record Dates
Last Update Posted: March 17, 2022
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Keros Therapeutics, Inc.:
Thrombocytopenia
Anemia
Red blood cells
Bone marrow
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases