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

Myelofibrosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05037760
• Other study ID #: KER050-MF-301
• Status: Recruiting
• Phase: Phase 2
• Start date: December 16, 2021
• Est. completion date: June 2025

Study information

• Verified date: August 2021
• Source: Keros Therapeutics
• Contact: Rachael Ryzman
• Phone: 603-548-3907
• Email: KER050-MF-301[@]kerostx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: June 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-ß 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

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• KER-050 monotherapy
KER-050 administered (SC) for up to 13 cycles
• KER-050 in combination with ruxolitinib
KER-050 administered (SC) for up to 13 cycles in combination with standard of care ruxolitinib

Locations

Country	Name	City	State
Australia	St. Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	The Tweed Hospital	Tweed Heads	New South Wales
Australia	Ballarat Oncology & Hematology Service	Wendouree	Victoria
Australia	Flinders Medical Centre	Woodville South	South Australia

Sponsors (2)

Lead Sponsor	Collaborator
Keros Therapeutics	IQVIA Biotech

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Proportion of participants with progression to AML (bone marrow blasts >20%)		At Week 24 and at Week 52
Secondary	Proportion of participants with progression to accelerated MF (bone marrow blasts =10%)		At Week 24 and at Week 52