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

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ClinicalTrials.gov Identifier: NCT04419649
Recruitment Status : Recruiting
First Posted : June 5, 2020
Last Update Posted : March 12, 2024
Sponsor:
Information provided by (Responsible Party):
Keros Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE June 3, 2020
First Posted Date  ICMJE June 5, 2020
Last Update Posted Date March 12, 2024
Actual Study Start Date  ICMJE August 19, 2020
Estimated Primary Completion Date June 30, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2023)
Incidence of adverse events (AEs) and serious adverse events (SAEs). [ Time Frame: From treatment initiation to end of study, approximately 2 years ]
Type, frequency, severity of AEs and relationship of AEs to KER-050
Original Primary Outcome Measures  ICMJE
 (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
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2023)
  • Maximum concentrations of KER-050 [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years ]
    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, approximately 2 years ]
    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.
  • Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years ]
    Change in baseline laboratory assessments prior to treatment with KER-050 and after treatment with KER-050
  • Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria [ Time Frame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years ]
    Change in baseline bone marrow assessments prior to treatment with KER-050 and after treatment with KER-050
  • 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, approximately 2 years ]
    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, approximately 2 years ]
    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, approximately 2 years ]
    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, approximately 2 years ]
    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, approximately 2 years ]
    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, approximately 2 years ]
    Change in baseline RBC counts and reticulocytes prior to treatment with KER-050 and after treatment with KER-050
Original Secondary Outcome Measures  ICMJE
 (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  ICMJE A Study of KER-050 to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Ascending dose study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelodysplastic Syndromes
  • Cytopenia
Intervention  ICMJE Drug: KER-050
KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles in a Long-Term Extension.
Study Arms  ICMJE
  • Experimental: KER-050 Cohort 1
    Escalating doses of KER-050 administered subcutaneously 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. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.
    Intervention: Drug: KER-050
  • Experimental: KER-050 Cohort 2
    Escalating doses of KER-050 administered subcutaneously 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. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.
    Intervention: Drug: KER-050
  • Experimental: KER-050 Cohort 3
    Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.
    Intervention: Drug: KER-050
  • Experimental: KER-050 Cohort 4
    Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.
    Intervention: Drug: KER-050
  • Experimental: KER-050 Cohort 5
    Escalating doses of KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.
    Intervention: Drug: KER-050
  • Experimental: KER-050 Dose Confirmation Cohort
    Participants to receive KER-050 administered subcutaneously every 4 weeks for up to 24 cycles. Eligible participants may be able to continue to receive subcutaneously administered KER-050 after completing 24 cycles.
    Intervention: Drug: KER-050
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 13, 2023)
140
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2020)
54
Estimated Study Completion Date  ICMJE November 30, 2025
Estimated Primary Completion Date June 30, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 count <13,000/µL.
  4. Anemia defined as:

    1. In non-transfused participants, having received no red blood cell (RBC) transfusions within 8 weeks Hgb concentration ≤ 10.0 g/dL OR
    2. In LTB participants, having received 1 to 3 units RBCs for Hgb ≤ 9.0 g/dL within 8 weeks OR
    3. 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Study Team +1 (617) 314-6297 ker050-md-201@kerostx.com
Listed Location Countries  ICMJE Australia,   Czechia,   France,   Germany,   Israel,   New Zealand,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04419649
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Current Responsible Party Keros Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Keros Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Keros Therapeutics, Inc.
Verification Date March 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP