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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

30 Apr 2022 → ongoing

Decision date (initial)

2024-09-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas Inc.

External identifiers

EU CT number

2023-507469-24-00

EudraCT number

2021-001838-19

WHO UTN

U1111-1294-3762

ClinicalTrials.gov

NCT04419649

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Efficacy, Others, Safety

Part 1: Dose Escalation
• To evaluate the safety and tolerability of ascending doses of elritercept in participants with very low, low, or intermediate risk MDS in order to determine the dose(s) that will be evaluated in Part 2 of the study.
Part 2: Dose Confirmation
• To confirm the safety and tolerability of the dose(s) selected in Part 1. Long-Term Extension
•To evaluate the long-term safety and tolerability of elritercept in participants with very low, low, or intermediate risk MDS in the Long term Extension (LTE).

Secondary objectives 3

1. Safety Objective: • To evaluate the progression to higher risk MDS or acute myeloid leukemia (AML)
2. Efficacy Objective: •To evaluate the efficacy of elritercept on anemia in participants with very low, low, or intermediate risk MDS, separately for ring sideroblast (RS)- positive and non-RS populations
3. Pharmacodynamic Objective: •To evaluate the pharmacodynamic (PD) effects of elritercept on erythropoiesis in participants with very low, low, or intermediate risk MDS, separately for RS-positive and non-RS populations.

Conditions and MedDRA coding

Anemia in Patients with Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS).

Study design 2 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003239-PIP01-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Diagnosis of MDS (Parts 1 and 2) according to WHO classification that meets International Prognostic Scoring System-Revised (IPSS-R) classification of very low, low, or intermediate risk disease.
2. < 5% blasts in bone marrow during the Pretreatment Period.
3. Peripheral blood white blood cell (WBC) count < 13,000/μL during the Pretreatment Period.
4. Anemia defined as: A). In non-transfused participants, having received no RBC transfusions within 8 weeks, Hgb concentration ≤ 10.0 g/dL during the Pretreatment Period OR B).a. In LTB participants, having received 1 to 3 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks of the Pretreatment Period OR C). In HTB participants, having received ≥ 4 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks of the Pretreatment Period.
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 highly effective methods of contraception.

Exclusion criteria 20

1. Active infection requiring parenteral antibiotic therapy within 28 days prior to C1D1 or oral antibiotics within 14 days of C1D1. Prophylactic antibiotics and/or antifungals for neutropenia are allowed.
2. Pregnant or lactating females.
3. Medical history: Diagnosis of MDS with deletion of chromosome 5q (Del5q).
4. Medical history: Presence of uncontrolled heart disease or New York Heart Association Class III or IV heart failure.
5. Medical history: Presence of uncontrolled hypertension (Grade >/= 2 high blood pressure).
6. Diagnosis of secondary MDS (ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases).
7. Medical history: Any malignancy other than MDS that has not been in remission and/or has required systemictherapy 1 year prior to C1D1 (or C5D1 for the Part 1 Extension).
8. Medical history: History of solid organ or hematological transplantation
9. Medical history: Body mass index >/= 40 kg/m2 during the pretreatment period.
10. Treatment history: Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept.
11. Treatment history: Treatment with ESA within 8 weeks prior to C1D1 (or C5D1 for the Part 1 Extension).
12. Treatment history for part 2: Prior treatment with luspatercept (Cohorts A, B, C, D, E, and F only)
13. Treatment history: Prior or concurrent chronic treatment with granulocyte colony stimulating factor (G-CSF) orgranulocyte-macrophage colony stimulating factor (GM-CSF), for reasons other than the treatment of MDS.
14. Platelet count > 450 x 10*9/L or < 30 x 10*9/L.
15. Transferrin saturation < 15%.
16. Ferritin < 50 μg/L.
17. Folate < 4.5 nmol/L (< 2.0 ng/mL).
18. Vitamin B12 < 148 pmol/L (< 200 pg/mL).
19. Estimated glomerular filtration rate (GFR) < 30 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI].
20. For Cohort G ONLY (for part 2): 1. Any luspatercept related AE Grade ≥ 3 that has not resolved to baseline or Grade ≤1 2. No history of allergy/anaphylaxis/hypersensitivity to luspatercept. 3. No prior treatment with imetelstat.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1 and Part 2: • Safety and tolerability as determined by the incidence of treatment emergent adverse events(TEAEs) and serious adverse events (SAEs).
2. Long-term Extension: •Safety and tolerability as determined by the incidence of TEAEs and SAEs over time

Secondary endpoints 13

1. Incidence of progression to higher risk MDS or AML per World Health Organization (WHO) 2016 criteria.
2. Proportion of low transfusion burden (LTB) and high transfusion burden (HTB) participants who achieve red blood cell (RBC) transfusion independence (TI) ≥ 8 weeks, overall and by RS status.
3. Proportion of participants who achieve modified 2006 International Working Group (IWG) Hematologic Improvement-Erythroid (HI E) response overall and by RS status (See Table 3 in Protocol KER050-MD-201 v 7.0).
4. Efficacy Endpoint: Proportion of participants who achieve overall erythroid response, defined as either HI-E or TI over any 8-week period, overall and by RS status
5. Efficacy Endpoint: Proportion of participants who achieve erythropoietic improvement overall and by RS status (See Table 3 in Protocol KER050-MD-201 v 7.0).
6. Efficacy Endpoint: Mean change from Baseline in Hgb by visit
7. Efficacy Endpoint: Time to HI-E response.
8. Efficacy Endpoint: Duration of HI-E response.
9. Efficacy Endpoint: Time to TI response.
10. Efficacy Endpoint: Time to TI response.
11. Efficacy Endpoint: Proportion of LTB and HTB participants who achieve TI ≥ 12 weeks, 16 weeks, 24 weeks, 48 weeks.
12. Proportion of LTB and HTB participants who achieve TI ≥ 12 weeks, 16 weeks, 24 weeks, 48 weeks.
13. Pharmacodynamic Endpoint: Change from baseline of red cell parameters, including reticulocyte count, mean corpuscular volume, mean corpuscular hemoglobin, and reticulocyte cell Hgb by visit.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

500 Kendall Street

City

Cambridge

Postcode

02142-1108

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 12

Locations

4 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 53 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications