Myelfibrosis (MF) MF- associated cytopenias MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10002272 Term: Anemia System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 21.0 Level: LLT Classification code 10074690 Term: Post essential thrombocythemia myelofibrosis System Organ Class:
Conditions
Interventions
Product Name: KER-050
Product Code: PRD8997233
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PRD8997233
Current Sponsor code: KER-050
Other descriptive name: KER-050
Concentration u
Sponsors
Keros Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female =18 years of age, at the time of signing informed consent. • Eastern Cooperative Oncology Group (ECOG) performance score =2. • Life expectancy =12 months per Investigator assessment • 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) and per the Investigator discontinued due to relapse, refractory, intolerance, or no longer met the benefit/risk ratio to continue on JAK inhibitor(s) treatment or ineligibility for JAK inhibitor(s) treatment or DIPSS intermediate 1 or higher disease and ineligible for JAK inhibitor in the opinion of investigator. • Anemia, defined as hemoglobin =10 g/dL during screening, or receiving RBC transfusions Arm 2A: • Previously treated with JAK inhibitor(s) • Anemia, defined as hemoglobin =10 g/dL during screening, or receiving RBC transfusions Arms 1B and 2B (note: sites in France will not participate in Arm 1B of the study): • 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: • Presence of the following cardiac conditions: a. New York Heart Association Class 3 or 4 heart failure b. QTcF >500 msec on the screening or C1D1 electrocardiogram (ECG) c. Uncontrolled clinically significant arrhythmia (participants with rate controlled atrial fibrillation are not excluded) d. Acute myocardial infarction or unstable angina pectoris 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: a. Erythropoiesis stimulating agent (ESA) b. Granulocyte colony-stimulating factor (G-CSF) c. Granulocyte-macrophage colony-stimulating factor (GM-CSF) d. Thrombopoietin agonists (TPO) e. Immunomodulator imide drugs (IMiDs; e.g., thalidomide, pomalidomide, lenalidomide) f. Interferon • Newly initiated iron chelation therapy within the 8 weeks prior to C1D1. • Treatment with another investigational drug or device or approved therapy for investigational use given for treatment of MF or anemia in MF =28 days prior to C1D1, or if the half-life of the previous product is known, within 5 times the half-life prior to C1D1, or whichever is longer. • Treatment with strong cytochrome P450 (CYP)3A4 inhibitors within 2 weeks prior to C1D1 (for Arms 1B and 2B) • Estimated glomerular filtration rate (eGFR) <40 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 Dose Escalation: •To evaluate the safety and tolerability of ascending doses of KER-050 monotherapy in participants with primary myelofibrosis (PMF), post-essential thrombocythemia myelofibrosis (post-ET MF), and post-polycythemia vera myelofibrosis (post-PV MF) who have anemia, and to determine the dose that will be evaluated in Part 2 of the study •To evaluate the safety and tolerability of ascending doses of KER-050 in combination with ruxolitinib in participants with PMF, post-ET MF, and post-PV MF who have anemia, and to determine the dose that will be evaluated in Part 2 of the study Part 2 Dose Expansion: •To evaluate the safety and tolerability of the dose(s) selected in Part 1 ;Secondary Objective: •To evaluate the PK of KER-050 administered with or without ruxolitinib in participants with PMF/post-ET MF/post-PV MF •To evaluate the PD effects related to erythropoiesis of KER-050 administered with or without ruxolitinib in participants with PMF/post-ET MF/post-PV MF •To evaluate the effect on anemia of KER-050 administered with or without ruxolitinib in participants with PMF/post-ET MF/post-PV MF •To evaluate the effect on MF disease manifestations and symptoms of KER-050 administered with or without ruxolitinib in participants with PMF/post-ET MF/post-PV MF •To evaluate the effect of KER-050 administered with or without ruxolitinib on progression to acute myeloid leukemia (AML) or accelerated MF Additional exploratory objective can be found in the Protocol. ;Primary end point(s): •Safety and tolerability as determined by the incidence of AEs, including severe AEs and SAEs;Timepoint(s) of evaluation of this end point: 64 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Proportion of participants with mean hemoglobin increase =1.5 g/dL or =2.0 g/dL from baseline over a period of >12 consecutive weeks within the first 24 weeks of study in subgroup of transfusion-independent participants • Proportion of participants with decrease in number of RBC transfusions from baseline over a period of >12 consecutive weeks within the first 24 weeks of study in subgroup of participants with anemia requiring RBC transfusions [Time Frame: Week 24] Evaluate PK • Plasma concentrations of KER-050 • AUClast • Accumulation rate (Rac) and assessment of steady-state as possible [Time Frame: 52 Weeks];Timepoint(s) of evaluation of this end point: Timepoints indicated above. | — |
Countries
Australia, Brazil, France, Italy, Korea, Republic of, Russian Federation, Spain, United Kingdom
Contacts
Public ContactCentral Contact Person
Keros Therapeutics, Inc.
Outcome results
None listed