None listed
Conditions
Brief summary
KER-050 is being developed by Keros Therapeutics Australia Pty Ltd as a potential treatment for anaemia in patients with very low, low or intermediate risk myelodysplastic syndromes (MDS). KER-050 is a therapeutic protein designed to increase red blood cell and platelet production by inhibiting the signaling of a subset of the TGF-ß family of proteins to promote hematopoiesis. The main purpose of this study is to test how safe the study drug is and how well the body can handle taking it (called tolerability). The study will also look at whether the study drug works (called efficacy), the amount of the study drug in the blood (called pharmacokinetics) and how the study drug affects the body (called pharmacodynamics).
Interventions
Participants in all cohorts will receive Investigational Medicinal Product (IMP) KER-050, administered subcutaneously (SC), every 4 weeks for up to 4 cycles, through Week 13.
The study contains two parts:
Part 1 Dose Escalation will consist of 4 cohorts ranging from a proposed dose level of .75 mg/kg to 3.75 mg/kg in approximately 6 participants per cohort.
Part 2 Dose Confirmation will consist of a single cohort at a dose level to be determined based on Part 1 in approximately 18-30 participan
Participants in all cohorts will receive Investigational Medicinal Product (IMP) KER-050, administered subcutaneously (SC), every 4 weeks for up to 4 cycles, through Week 13. The study contains two parts: Part 1 Dose Escalation will consist of 4 cohorts ranging from a proposed dose level of .75 mg/kg to 3.75 mg/kg in approximately 6 participants per cohort. Part 2 Dose Confirmation will consist of a single cohort at a dose level to be determined based on Part 1 in approximately 18-30 participants. The study is open label, sequentially assigning participants to cohorts.
Sponsors
Keros Therapeutics Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female > or = 18 years of age, at the time of signing informed consent. 2. Diagnosis of MDS according to World Health Organization (WHO)/French American British (FAB) classification that meets Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease. 3. < 5% blasts in bone marrow. 4. Peripheral blood white blood cell (WBC) count < 13,000/µL. 5. Anemia defined as: - In LTB participants (defined as having received < 4 units of RBCs within 8 weeks), mean hemoglobin concentration < 10.0 g/dL of two measurements (one performed within 1 day prior to Cycle 1 Day 1 and the other performed 7-28 days prior, not influenced by RBC transfusion within 7 days of measurement) OR - In HTB participants (defined as requiring > or = 4 units of RBCs for hemoglobin < or = 9.0 g/dL within 8 weeks) 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia). 7. Females of child-bearing potential and sexually active males must agree to use effective methods of contraception.
Exclusion criteria
1. Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1. 2. Diagnosis of secondary MDS (ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases). 3. Vitamin B12 deficiency. 4. Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept. 5. Treatment within 28 days prior to Cycle 1 Day 1 with: a. Erythropoiesis stimulating agent (ESA) OR b. Granulocyte colony-stimulating factor (G-CSF) OR c. Granulocyte-macrophage colony-stimulating factor (GM-CSF) 6. Iron chelation therapy if initiated within 8 weeks prior to Cycle 1 Day 1. 7. Vitamin B12 therapy within 8 weeks prior to Cycle 1 Day 1. 8. Treatment with another investigational drug or device or approved therapy for investigational use < or = 28 days prior to Cycle 1 Day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer. 9. Platelet count > 450 x 10*9/L or < 30 x 10*9/L. 10. Transferrin saturation < 15%. 11. Ferritin < 50 µg/L. 12. Folate < 4.5 nmol/L (< 2.0 ng/mL). 13. Vitamin B12 < 148 pmol/L (< 200 pg/mL). 14. Estimated glomerular filtration rate (GFR) < 40 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]. 15. Pregnant or lactating females.
Outcome results
None listed