Clinical trial NCT04419649: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Cytopenia
Keywords: transfusion
Lead sponsor: Keros Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-05
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Ascending dose study
Primary purpose: TREATMENT

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).

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 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

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs).
timeFrame: From treatment initiation to end of study, approximately 2 years
Secondary outcomes:
measure: Maximum concentrations of KER-050
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Erythroid response in low-transfusion burden (LTB) and high-transfusion burden (HTB) participants.
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Incidence of progression to higher risk MDS or AML per World Health Organization 2016 criteria
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Modified 2006 International Working Group (IWG) Hematologic Improvement Erythroid (HI-E) response
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Mean change from baseline in hemoglobin
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Time to erythroid response and modified 2006 IWG HI-E response
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Duration of erythroid response and modified 2006 IWG HI-E response
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Frequency of red blood cell (RBC) transfusions and rate of RBC transfusion independence ≥ 8 weeks
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
measure: Change from Baseline in RBC counts and reticulocytes
timeFrame: Measured at multiple timepoints over the course of study from study day 1 to end of study, approximately 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Miami
country: United States
facility: University of Miami, Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Center
state: Florida
city: Lansing
country: United States
facility: Karmanos Cancer Institute at McLaren Greater Lansing
state: Michigan
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Health Center
state: Pennsylvania
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
state: New South Wales
city: Tweed Heads
country: Australia
facility: The Tweed Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Douglas
country: Australia
facility: Townsville University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Geelong
country: Australia
facility: University Hospital Geelong
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Wendouree
country: Australia
facility: Ballarat Oncology and Haematology Service
state: Victoria
city: Brno
country: Czechia
facility: Fakultni Nemocnice Brno
city: Praha
country: Czechia
facility: Fakultni Nemocnice Kralovske Vinohrady
city: Praha
country: Czechia
facility: Vseobecna Fakultni Nemocnice Praha
city: Angers
country: France
facility: CHU Angers - Hôpital Hôtel Dieu
city: Nantes
country: France
facility: CHU de Nantes - Hotel Dieu
city: Nice
country: France
facility: CHU Nice - Hôpital de l'Archet
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Pontoise
country: France
facility: CH René-Dubos
city: Talence
country: France
facility: CHU de Bordeaux - Hôpital Haut-Lévêque
city: Épagny
country: France
facility: Centre Hospitalier de la Région d'Annecy
city: Bayreuth
country: Germany
facility: Klinikum Bayreuth GmbH
city: Düsseldorf
country: Germany
facility: Marien Hospital Dusseldorf GMBH
city: Düsseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf AoeR
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
city: Rostock
country: Germany
facility: Universitaetsmedizin Rostock
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Auckland
country: New Zealand
facility: Middlemore Hospital
city: Barcelona
country: Spain
facility: Hospital Universitario Central de Asturias
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
Study officials:
References: