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

Myelodysplastic Syndromes Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04419649
• Other study ID #: KER050-MD-201
• Status: Recruiting
• Phase: Phase 2
• Start date: August 19, 2020
• Est. completion date: November 30, 2025

Study information

• Verified date: March 2024
• Source: Keros Therapeutics, Inc.
• Contact: Clinical Study Team
• Phone: +1 (617) 314-6297
• Email: ker050-md-201[@]kerostx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: November 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cytopenia
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Border Medical Oncology Research Unit	Albury	New South Wales
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Townsville University Hospital	Douglas	Queensland
Australia	University Hospital Geelong	Geelong	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	St Vincent's Hospital Melbourne	Melbourne	Victoria
Australia	The Tweed Hospital	Tweed Heads	New South Wales
Australia	Ballarat Oncology and Haematology Service	Wendouree	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Czechia	Fakultni Nemocnice Brno	Brno
Czechia	Fakultni Nemocnice Kralovske Vinohrady	Praha
Czechia	Vseobecna Fakultni Nemocnice Praha	Praha
France	CHU Angers - Hôpital Hôtel Dieu	Angers
France	Centre Hospitalier de la Région d'Annecy	Épagny
France	CHU de Nantes - Hotel Dieu	Nantes
France	CHU Nice - Hôpital de l'Archet	Nice
France	Hôpital Saint-Louis	Paris
France	CH René-Dubos	Pontoise
France	CHU de Bordeaux - Hôpital Haut-Lévêque	Talence
Germany	Klinikum Bayreuth GmbH	Bayreuth
Germany	Marien Hospital Dusseldorf GMBH	Düsseldorf
Germany	Universitaetsklinikum Duesseldorf AoeR	Düsseldorf
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	Universitaetsklinikum Leipzig AoeR	Leipzig
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz
Germany	Universitaetsmedizin Rostock	Rostock
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
New Zealand	Middlemore Hospital	Auckland
Spain	Hospital Universitario Central de Asturias	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	Barcelona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitari i Politecnic La Fe	Valencia
United States	City of Hope National Medical Center	Duarte	California
United States	Karmanos Cancer Institute at McLaren Greater Lansing	Lansing	Michigan
United States	University of Miami, Sylvester Comprehensive Cancer Center	Miami	Florida
United States	University of Pittsburgh Medical Health Center	Pittsburgh	Pennsylvania
United States	H. Lee Moffitt Cancer Center and Research Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Keros Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  France,  Germany,  Israel,  New Zealand,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AEs) and serious adverse events (SAEs).	Type, frequency, severity of AEs and relationship of AEs to KER-050	From treatment initiation to end of study, approximately 2 years
Secondary	Maximum concentrations of KER-050	Pharmacokinetics of KER-050	Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
Secondary	Erythroid response in low-transfusion burden (LTB) and high-transfusion burden (HTB) participants.	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
Secondary	Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria	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
Secondary	Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria	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
Secondary	Modified 2006 International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response	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
Secondary	Mean change from baseline in hemoglobin	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
Secondary	Time to erythroid response and modified 2006 IWG HI-E response	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
Secondary	Duration of erythroid response and modified 2006 IWG HI-E response	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
Secondary	Frequency of red blood cell (RBC) transfusions and rate of RBC transfusion independence = 8 weeks	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
Secondary	Change from Baseline in RBC counts and reticulocytes	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