A Phase 2, Open-Label, Ascending Dose Study of KER-050 for the Treatment of Anemia in Patients with Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS)
- Conditions
- Anemia in Patients with Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS).MedDRA version: 21.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10002272Term: AnemiaSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2021-001838-19-ES
- Lead Sponsor
- Keros Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 104
1. 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.
2. < 5% blasts in bone marrow.
3. Peripheral blood white blood cell (WBC) count < 13,000/µL.
4. Anemia defined as:
a. 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
b. In HTB participants (defined as requiring > or = 4 units of RBCs for hemoglobin < or = 9.0 g/dL within 8 weeks)
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia.
6. Females of child-bearing potential and sexually active males must agree to use effective methods of contraception.
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 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Part 1: Dose Escalation<br>• To evaluate the safety and tolerability of ascending doses of KER-050 in participants with very low, low, or intermediate risk MDS in order to determine the dose(s) that will be evaluated in Part 2 of the study.<br>Part 2: Dose Confirmation<br>• To confirm the safety and tolerability of the dose(s) selected in Part 1.;Secondary Objective: Secondary Objectives (Part 1 and Part 2)<br>• To evaluate the PD effects of KER-050 on erythropoiesis in participants with very low, low, or intermediate risk MDS, separately for ring sideroblast (RS) positive and non-RS populations.<br>• To evaluate the efficacy of KER-050 on anemia in participants with very low, low or intermediate risk MDS, separately for RS positive and non-RS populations.;Primary end point(s): Primary Endpoint:<br>Safety and tolerability as determined by the incidence of adverse events (AEs) and serious AEs (SAEs).;Timepoint(s) of evaluation of this end point: 105 Weeks
- Secondary Outcome Measures
Name Time Method