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

Keros Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Cytopenia; Myelodysplastic Syndromes

Treatments: Drug: KER-050

Study type: Interventional

Funder types: Industry

Identifiers

NCT04419649

KER050-MD-201

Details and patient eligibility

About

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.

Full 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).

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

140 participants in 6 patient groups

KER-050 Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: KER-050

KER-050 Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: KER-050

KER-050 Cohort 3

Experimental group

Description:

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.

Treatment:

Drug: KER-050

KER-050 Cohort 4

Experimental group

Description:

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.

Treatment:

Drug: KER-050

KER-050 Cohort 5

Experimental group

Description:

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.

Treatment:

Drug: KER-050

KER-050 Dose Confirmation Cohort

Experimental group

Description:

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.

Treatment:

Drug: KER-050