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

Phase 2

Recruiting

• Conditions: Myelodysplastic Syndromes; Cytopenia
• Interventions: Drug: KER-050

• Registration Number: NCT04419649
• Lead Sponsor: Keros Therapeutics, Inc.

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 Timeline

• Study First Submitted: 2020-06-03
• Study First Submitted QC: 2020-06-03
• Study First Posted: 2020-06-05
• Study Start: 2020-08-19
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-24
• Last Update Posted: 2024-06-25
• Primary Completion: 2025-06-30
• Study Completion: 2025-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 140

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
KER-050 Cohort 3	KER-050	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 Cohort 5	KER-050	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 Cohort 1	KER-050	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 Cohort 2	KER-050	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 Cohort 4	KER-050	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 Dose Confirmation Cohort	KER-050	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.

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (AEs) and serious adverse events (SAEs).	From treatment initiation to end of study, approximately 2 years	Type, frequency, severity of AEs and relationship of AEs to KER-050

Secondary Outcome Measures

Name	Time	Method
Maximum concentrations of KER-050	Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years	Pharmacokinetics of KER-050
Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria	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
Time to erythroid response and modified 2006 IWG HI-E response	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
Change from Baseline in RBC counts and reticulocytes	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
Erythroid response in low-transfusion burden (LTB) and high-transfusion burden (HTB) participants.	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.
Modified 2006 International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response	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	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
Duration of erythroid response and modified 2006 IWG HI-E response	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	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

Trial Locations

Locations (43)

Box Hill Hospital; 🇦🇺 Box Hill, Victoria, Australia

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

University of Pittsburgh Medical Health Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Karmanos Cancer Institute at McLaren Greater Lansing; 🇺🇸 Lansing, Michigan, United States

University of Miami, Sylvester Comprehensive Cancer Center; 🇺🇸 Miami, Florida, United States

Border Medical Oncology Research Unit; 🇦🇺 Albury, New South Wales, Australia

The Tweed Hospital; 🇦🇺 Tweed Heads, New South Wales, Australia

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Townsville University Hospital; 🇦🇺 Douglas, Queensland, Australia

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

St Vincent's Hospital Melbourne; 🇦🇺 Melbourne, Victoria, Australia

CHU Angers - Hôpital Hôtel Dieu; 🇫🇷 Angers, France

Vseobecna Fakultni Nemocnice Praha; 🇨🇿 Praha, Czechia

Fakultni Nemocnice Brno; 🇨🇿 Brno, Czechia

Fakultni Nemocnice Kralovske Vinohrady; 🇨🇿 Praha, Czechia

CHU Nice - Hôpital de l'Archet; 🇫🇷 Nice, France

CHU de Nantes - Hotel Dieu; 🇫🇷 Nantes, France

CH René-Dubos; 🇫🇷 Pontoise, France

Hôpital Saint-Louis; 🇫🇷 Paris, France

CHU de Bordeaux - Hôpital Haut-Lévêque; 🇫🇷 Talence, France

Centre Hospitalier de la Région d'Annecy; 🇫🇷 Épagny, France

Klinikum Bayreuth GmbH; 🇩🇪 Bayreuth, Germany

Universitaetsklinikum Duesseldorf AoeR; 🇩🇪 Düsseldorf, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; 🇩🇪 Mainz, Germany

Marien Hospital Dusseldorf GMBH; 🇩🇪 Düsseldorf, Germany

Universitaetsklinikum Leipzig AoeR; 🇩🇪 Leipzig, Germany

Klinikum Esslingen GmbH; 🇩🇪 Esslingen, Germany

Universitaetsmedizin Rostock; 🇩🇪 Rostock, Germany

Middlemore Hospital; 🇳🇿 Auckland, New Zealand

Hospital Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario Central de Asturias; 🇪🇸 Barcelona, Spain

ICO l'Hospitalet - Hospital Duran i Reynals; 🇪🇸 Barcelona, Spain

Hospital Universitari i Politecnic La Fe; 🇪🇸 Valencia, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Tel-Aviv Sourasky Medical Center; 🇮🇱 Tel Aviv, Israel

Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel

Austin Health; 🇦🇺 Heidelberg, Victoria, Australia

Ballarat Oncology and Haematology Service; 🇦🇺 Wendouree, Victoria, Australia

University Hospital Geelong; 🇦🇺 Geelong, Victoria, Australia

H. Lee Moffitt Cancer Center and Research Center; 🇺🇸 Tampa, Florida, United States