A Study of KER-050 to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes

• ClinicalTrials.gov Identifier: NCT04419649
• Recruitment Status: Recruiting
• First Posted: June 5, 2020
• Last Update Posted: November 17, 2022
• Sponsor: Keros Therapeutics, Inc.
• Information provided by (Responsible Party): Keros Therapeutics, Inc.

Tracking Information

• First Submitted Date: June 3, 2020
• First Posted Date: June 5, 2020
• Last Update Posted Date: November 17, 2022
• Actual Study Start Date: August 19, 2020
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 13, 2022)

Incidence of adverse events (AEs) and serious adverse events (SAEs). [ Time Frame: From treatment initiation to End of Study visit (approximately 97 weeks) ]

Type, frequency, severity of AEs and relationship of AEs to KER-050

Original Primary Outcome Measures (submitted: June 3, 2020)

Incidence of adverse events (AEs) and serious adverse events (SAEs). [ Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks) ]

Type, frequency, severity of AEs and relationship of AEs to KER-050

Current Secondary Outcome Measures (submitted: April 13, 2022)

• Maximum concentrations of KER-050 [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to End of Study visit (approximately 97 weeks) ]
  Pharmacokinetics of KER-050
• Erythroid response in low-transfusion burden (LTB) and high-transfusion burden (HTB) participants. [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to End of Study visit (approximately 97 weeks) ]
  In LTB participants, the proportion of participants who have a hemoglobin increase of ≥ 1.5 g/dL from Baseline for ≥ 14 days (in the absence of RBC transfusions). In HTB participants, the proportion of participants having a reduction of ≥ 50% or ≥ 4 RBC units transfused compared to pretreatment over an 8-week period.
• Modified 2006 International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to End of Study visit (approximately 97 weeks) ]
  In LTB participants, the proportion of participants with an increase of ≥ 1.5 g/dL from pretreatment hemoglobin during any 8-week period on study compared to Baseline. In HTB participants, the proportion of participants having a reduction by ≥ 4 units of RBCs transfused (for a hemoglobin ≤ 9.0 g/dL) during any 8-week period on study, compared with the 8-week period prior to study Cycle 1 Day 1.
• Mean change from baseline in hemoglobin [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to End of Study visit (approximately 97 weeks) ]
  Change in baseline hemoglobin prior to treatment with KER-050 and after treatment with KER-050
• Time to erythroid response and modified 2006 IWG HI-E response [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to End of Study visit (approximately 97 weeks) ]
  Time to erythroid response prior to treatment with KER-050 and after treatment with KER-050
• Duration of erythroid response and modified 2006 IWG HI-E response [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to End of Study visit (approximately 97 weeks) ]
  Duration of erythroid response prior to treatment with KER-050 and after treatment with KER-050
• Frequency of red blood cell (RBC) transfusions and rate of RBC transfusion independence ≥ 8 weeks [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to End of Study visit (approximately 97 weeks) ]
  Frequency and rate of RBC transfusions prior to treatment with KER-050 and after treatment with KER-050
• Change from Baseline in RBC counts and reticulocytes [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to End of Study visit (approximately 97 weeks) ]
  Change in baseline RBC counts and reticulocytes prior to treatment with KER-050 and after treatment with KER-050

Original Secondary Outcome Measures (submitted: June 3, 2020)

• Maximum concentrations of KER-050 [ Time Frame: Measured at multiple timepoints over the course of treatment from study day 1 to approximately 15 weeks ]
  Pharmacokinetics of KER-050
• Erythroid response in low-transfusion burden (LTB) and high-transfusion burden (HTB) participants. [ Time Frame: Measured over the course of study, up to approximately 25 weeks from study day 1 ]
  In LTB participants, the proportion of participants who have a hemoglobin increase of ≥ 1.5 g/dL from Baseline for ≥ 14 days (in the absence of RBC transfusions). In HTB participants, the proportion of participants having a reduction of ≥ 50% or ≥ 4 RBC units transfused compared to pretreatment over an 8-week period.
• Modified 2006 International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response [ Time Frame: Measured over the course of study, up to approximately 25 weeks from study day 1 ]
  In LTB participants, the proportion of participants with an increase of ≥ 1.5 g/dL from pretreatment hemoglobin during any 8-week period on study compared to Baseline. In HTB participants, the proportion of participants having a reduction by ≥ 4 units of RBCs transfused (for a hemoglobin ≤ 9.0 g/dL) during any 8-week period on study, compared with the 8-week period prior to study Cycle 1 Day 1.
• Mean change in hemoglobin [ Time Frame: Measured over the course of study, up to approximately 25 weeks from study day 1 ]
• Time to erythroid response and modified 2006 IWG HI-E response [ Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks) ]
• Duration of erythroid response and modified 2006 IWG HI-E response [ Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks) ]
• Frequency of RBC transfusions and rate of RBC transfusion independence ≥ 8 weeks [ Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks) ]
• Change from Baseline in RBC counts and reticulocytes [ Time Frame: From treatment initiation to End of Study visit (approximately 25 weeks) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of KER-050 to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes
• Official Title: 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)
• Brief Summary: The purpose of this study is to evaluate the effects of KER-050 on anemia in patients with very low, low or intermediate risk MDS.
• Detailed Description: KER-050 is a 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).
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Ascending dose study

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Myelodysplastic Syndromes
• Cytopenia

Intervention

Drug: KER-050

KER-050 administered (SC) every 4 weeks for up to 24 cycles.

Study Arms

• Experimental: KER-050 Cohort 1
  Escalating doses of KER-050 administered subcutaneously (SC) every 4 weeks for up to 4 cycles. Participants have the option to continue to receive KER-050 once 4 cycles have been completed for up to 24 cycles.
  Intervention: Drug: KER-050
• Experimental: KER-050 Cohort 2
  Escalating doses of KER-050 administered subcutaneously (SC) every 4 weeks for up to 4 cycles. Participants have the option to continue to receive KER-050 once 4 cycles have been completed for up to 24 cycles.
  Intervention: Drug: KER-050
• Experimental: KER-050 Cohort 3
  Escalating doses of KER-050 administered subcutaneously (SC) every 4 weeks for up to 24 cycles.
  Intervention: Drug: KER-050
• Experimental: KER-050 Cohort 4
  Escalating doses of KER-050 administered subcutaneously (SC) every 4 weeks for up to 24 cycles.
  Intervention: Drug: KER-050
• Experimental: KER-050 Cohort 5
  Escalating doses of KER-050 administered subcutaneously (SC) every 4 weeks for up to 24 cycles.
  Intervention: Drug: KER-050
• Experimental: KER-050 Dose Confirmation Cohort
  Participants to receive KER-050 administered subcutaneously (SC) every 4 weeks for up to 24 cycles.
  Intervention: Drug: KER-050

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 13, 2022): 110
• Original Estimated Enrollment (submitted: June 3, 2020): 54
• Estimated Study Completion Date: November 30, 2025
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

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:

   • In non-transfused participants, having received no red blood cell (RBC) transfusions within 8 weeks Hgb concentration ≤ 10.0 g/dL OR
   • In LTB participants, having received 1 to 3 units RBCs for Hgb ≤ 9.0 g/dL within 8 weeks OR
   • In HTB participants, having received ≥ 4 units of RBCs for Hgb ≤ 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.

Key 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 (i.e., MDS 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:

   1. Erythropoiesis stimulating agent (ESA) OR
   2. Granulocyte colony-stimulating factor (G-CSF) OR
   3. 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Study Team; +1 (617) 314-6297; ker050-md-201@kerostx.com

• Listed Location Countries: Australia, Germany, Israel, New Zealand, Spain, United States

Administrative Information

• NCT Number: NCT04419649
• Other Study ID Numbers: KER050-MD-201
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Keros Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Keros Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Keros Therapeutics, Inc.
• Verification Date: November 2022