A Phase 3b Study of BMS-986346 in Lower-risk Myelodysplastic Syndrome Participants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

6 Mar 2024 → ongoing

Decision date (initial)

2024-02-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Celgene Corporation

External identifiers

EU CT number

2023-504541-31-00

WHO UTN

U1111-1289-6529

ClinicalTrials.gov

NCT06045689

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

The primary objective: to evaluate red blood cell transfusion independence (RBC-TI) with an associated concurrent mean hemoglobin (Hb) increase of ≥ 1 g/dL after luspatercept initiated at the maximum approved dose for the treatment of anemia due to IPSS-R very low-, low, or intermediate- risk who require RBC transfusions.

Secondary objectives 1

1. Main secondary efficacy objective: evaluate the effect of luspatercept on reduction in RBC transfusions and increase in Hb, duration of RBC-TI, and time to RBC TI in MDS participants. Main secondary safety objective: to assess the safety and tolerability of luspatercept in MDS participants using a dosing regimen starting at the highest approved dose of 1.75 mg/kg.

Conditions and MedDRA coding

Myelodysplastic syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Participants are eligible to be included in the study if all following criteria apply: A) Participant must be 18 years or older, have documented diagnosis of MDS, have an Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2. For Cohort 1 only: participant must have an endogenous serum erythropoietin (EPO) level of < 500 U/L and no prior ESA treatment. For Cohort 2 only: participant must be refractory or intolerant to prior ESA treatment as defined by any of the following: i) Refractory to prior ESA treatment: Documentation of nonresponse or response that was no longer maintained to prior ESA-containing regimen, either as a single agent or in combination (eg, with G-CSF). The ESA regimen must have been either: (1) Recombinant human erythropoietin ≥ 40,000 IU/week for at least 8 doses or equivalent; or 1050 mg/kg/week for at least 8 doses or equivalent OR (2) Darbepoetin- darbepoetin alpha ≥ 240 μg every week for at least 12-weeks or equivalent ii) Intolerant to prior ESA treatment: Documentation of discontinuation of prior ESA-containing regimen, either as a single agent or in combination (eg, with G-CSF), at any time after introduction due to intolerance or an AE. B) And must require RBC transfusion documented by the following criteria: i) Average transfusion requirement of ≥ 1 units of packed RBCs (pRBCs) confirmed for a minimum of 8-weeks immediately prior to first treatment of luspatercept ii) Hb levels at the time of or within 7 days prior to administration of an RBC transfusion must be ≤ 10.0 g/dL in order for the transfusion to be counted towards meeting eligibility criteria. RBC transfusions administered when Hb levels are > 10 g/dL and/or RBC transfusions administered for elective surgery do not qualify as a required transfusion for the purpose of meeting eligibility criteria

Exclusion criteria 1

1. A participant will be excluded from the study if they have a secondary MDS, known history of diagnosis of AML, prior allogenic or autologous stem cell transplant, history of allergy or hypersensitivity to study drug components, pregnant, plan to get pregnant or breastfeeding, prior history of malignancies, known significant anemia due to iron, vitamin B12 or folate deficiencies.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint: composite of achievement of RBC-TI for 8-weeks with a concurrent mean Hb increase of ≥ 1 g/dL from Week 1 to Week 24.

Secondary endpoints 2

1. Main secondary efficacy endpoints: mean change in total RBC units transfused over a fixed 16 week period from Week 9 to Week 24 and from Week 33 to Week 48. Time from first dose to first onset of RBC TI ≥ 8, 12, and 16 weeks, Maximum duration of RBC-TI for participants who achieve RBC TI ≥ 8- and 16-week period
2. Main secondary safety endpoint is the type, frequency, severity of AEs, and relationship of adverse events (AEs) to luspatercept from screening to 6 weeks (42-days) post last dose and from Week 1 to Week 48

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celgene Corp.

Sponsor organisation

Celgene Corp.

Address

Route 206 And Province Line Road

City

Princeton

Postcode

08543-4000

Country

United States

Scientific contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Public contact point

Organisation

Celgene Corp.

Contact name

GSM-CT

Third parties 10

Locations

7 EU/EEA countries · 37 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

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