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

March 11, 2024 updated by: Keros Therapeutics, Inc.

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)

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.

Study Overview

Status

Recruiting

Intervention / Treatment

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

Enrollment (Estimated)

140

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • New South Wales
      • Albury, New South Wales, Australia, 2640
        • Recruiting
        • Border Medical Oncology Research Unit
        • Contact:
          • Anish Puliyayil
      • Tweed Heads, New South Wales, Australia, 2485
        • Recruiting
        • The Tweed Hospital
        • Contact:
          • Alejandro Arbelaez
      • Westmead, New South Wales, Australia, 2145
        • Recruiting
        • Westmead Hospital
        • Contact:
          • John Kwan
    • Queensland
      • Douglas, Queensland, Australia, 4814
        • Recruiting
        • Townsville University Hospital
        • Contact:
          • Joel Wight
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Royal Adelaide Hospital
        • Contact:
          • Devendra Hiwase
      • Bedford Park, South Australia, Australia, 5042
        • Recruiting
        • Flinders Medical Centre
        • Contact:
          • David Ross, MD
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Recruiting
        • Box Hill Hospital
        • Contact:
          • Tse-Chieh Teh
      • Geelong, Victoria, Australia, 3220
        • Recruiting
        • University Hospital Geelong
        • Contact:
          • Hannah Rose
      • Heidelberg, Victoria, Australia, 3084
        • Recruiting
        • Austin Health
        • Contact:
          • Chun Fong
      • Melbourne, Victoria, Australia, 3050
        • Recruiting
        • Royal Melbourne Hospital
        • Contact:
          • Lynette Chee
      • Melbourne, Victoria, Australia, 3065
        • Recruiting
        • St Vincent's Hospital Melbourne
        • Contact:
          • Shuh Ying Tan
      • Wendouree, Victoria, Australia, 3355
        • Recruiting
        • Ballarat Oncology and Haematology Service
        • Contact:
          • George Kannourakis, MD
      • Brno, Czechia
        • Recruiting
        • Fakultní Nemocnice Brno
        • Contact:
          • Jiri Mayer
      • Praha, Czechia
        • Recruiting
        • Fakultni Nemocnice Kralovske Vinohrady
        • Contact:
          • Olga Cerna
      • Praha, Czechia
        • Recruiting
        • Vseobecna Fakultni Nemocnice Praha
        • Contact:
          • Anna Jonasova
      • Angers, France
        • Recruiting
        • CHU Angers - Hôpital Hôtel Dieu
        • Contact:
          • Sylvain Thepot
      • Nantes, France
        • Recruiting
        • CHU de Nantes - Hotel Dieu
        • Contact:
          • Alice Garnier
      • Nice, France
        • Recruiting
        • CHU Nice - Hôpital de l'Archet
        • Contact:
          • Thomas Cluzeau
      • Paris, France
        • Recruiting
        • Hopital Saint-Louis
        • Contact:
          • Lionel Ades
      • Pontoise, France
        • Recruiting
        • CH René-Dubos
        • Contact:
          • Riad Benramdane
      • Talence, France
        • Recruiting
        • CHU de Bordeaux - Hôpital Haut-Lévêque
        • Contact:
          • Sophie Dimicoli Salazar
      • Épagny, France
        • Recruiting
        • Centre Hospitalier de la Région d'Annecy
        • Contact:
          • Natacha Mauz
        • Contact:
          • Charlotte Doublet
      • Bayreuth, Germany
        • Recruiting
        • Klinikum Bayreuth GmbH
        • Contact:
          • Alexander Kiani
      • Düsseldorf, Germany
        • Recruiting
        • Marien Hospital Dusseldorf GMBH
        • Contact:
          • Aristoteles Giagounidis
      • Düsseldorf, Germany
        • Recruiting
        • Universitaetsklinikum Duesseldorf AoeR
        • Contact:
          • Ulrich Germing
      • Esslingen, Germany
        • Recruiting
        • Klinikum Esslingen GmbH
        • Contact:
          • Swen Wessendorf
      • Leipzig, Germany
        • Recruiting
        • Universitaetsklinikum Leipzig AoeR
        • Contact:
          • Anne Kubasch
      • Mainz, Germany
        • Recruiting
        • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
        • Contact:
          • Daniel Sasca
      • Rostock, Germany
        • Recruiting
        • Universitaetsmedizin Rostock
        • Contact:
          • Christoph Wittke
      • Ramat Gan, Israel, 52621
        • Recruiting
        • Sheba Medical Center
        • Contact:
          • Drorit Merkel
      • Tel Aviv, Israel, 6423906
        • Recruiting
        • Tel-Aviv Sourasky Medical Center
        • Contact:
          • Yakir Moshe
      • Auckland, New Zealand, 2025
        • Recruiting
        • Middlemore Hospital
        • Contact:
          • James Liang
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitario Vall d'Hebron
        • Contact:
          • David V Ferreiras
      • Barcelona, Spain
        • Recruiting
        • ICO l'Hospitalet - Hospital Duran i Reynals
        • Contact:
          • Montserrat Sangerman
      • Barcelona, Spain
        • Recruiting
        • Hospital Universitario Central de Asturias
        • Contact:
          • Teresa Bernal del Castillo
      • Salamanca, Spain
        • Recruiting
        • Hospital Universitario de Salamanca
        • Contact:
          • Maria Campelo
      • Sevilla, Spain
        • Recruiting
        • Hospital Universitario Virgen del Rocio
        • Contact:
          • Jose Gonzalez
      • Valencia, Spain
        • Recruiting
        • Hospital Universitari i Politecnic La Fe
        • Contact:
          • Guillermo Santillana
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope National Medical Center
        • Principal Investigator:
          • Andrew Artz
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami, Sylvester Comprehensive Cancer Center
        • Contact:
          • Mikkael A Sekeres, MD
        • Principal Investigator:
          • Mikkael A Sekeres, MD
      • Tampa, Florida, United States, 33612
        • Not yet recruiting
        • H. Lee Moffitt Cancer Center and Research Center
        • Contact:
          • Rami Komrokji
    • Michigan
      • Lansing, Michigan, United States, 48910
        • Not yet recruiting
        • Karmanos Cancer Institute at McLaren Greater Lansing
        • Principal Investigator:
          • Daniel Isaac
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Not yet recruiting
        • University of Pittsburgh Medical Health Center
        • Contact:
          • Robert Redner

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
From treatment initiation to end of study, approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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.

Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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
Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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
Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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.

Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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
Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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
Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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
Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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
Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
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
Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 19, 2020

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

November 30, 2025

Study Registration Dates

First Submitted

June 3, 2020

First Submitted That Met QC Criteria

June 3, 2020

First Posted (Actual)

June 5, 2020

Study Record Updates

Last Update Posted (Actual)

March 12, 2024

Last Update Submitted That Met QC Criteria

March 11, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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