Phase 2 Study of Luspatercept in Adults and Adolescents with Alpha (α)-thalassemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celgene Corp.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

30 Jan 2023 → ongoing

Decision date (initial)

2023-07-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Celgene Corporation

External identifiers

EU CT number

2022-502328-35-00

EudraCT number

2021-004928-15

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

Adult cohorts: To compare the erythroid response of luspatercept plus BSC vs placebo plus BSC on anemia in participants with A-THAL HbH disease.
Adolescent cohorts: To confirm the recommended safe and tolerable dose of luspatercept in adolescent participants with A-THAL

Secondary objectives 1

1. Adult cohorts: To compare the effect of Luspatercept plus BSC vs placebo plus BSC on RBC transfusion burden and anemia in participants with A-THAL. Adolescent cohorts: To evaluate the safety and pharmacokinetics of luspatercept in adolescent TD and NTD participants with A-THAL .

Conditions and MedDRA coding

Alpha (α)-thalassemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001521-PIP03-22

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Adult participant ≥ 18 years with documented diagnosis of α-thalassemia HbH disease with Transfusion dependence defined as: - TD participant: ≥ 6 RBC units during the 24 weeks prior to randomization and no transfusion-free period for > 56 days during the 24 weeks prior to randomization - NTD participant: < 6 RBC units during the 24 weeks prior to randomization and, RBC transfusion-free during at least 8 weeks prior to randomization and, mean baseline Hb ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to randomization; hemoglobin values within 21 days post-transfusion will be excluded. Adolescent participant 12 years to < 18 years with documented diagnosis of α- thalassemia HbH disease with transfusion dependence defined as: - TD participant: ≥ 4 RBC events during the 24 weeks prior to enrollment and, no transfusion-free period for > 56 days during the 24 weeks prior to enrollment. Participants must have a history of regular transfusions for at least 2 years - NTD participant: < 4 RBC events during the 24 weeks prior to enrollment and RBC transfusion-free during at least 8 weeks prior to enrollment and, mean baseline Hb ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to enrollment, hemoglobin values within 21 days post-transfusion will be excluded. - Participant has Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening.

Exclusion criteria 1

1. Key Exclusion Criteria - Adult and Adolescent participants: - Medical Conditions: Diagnosis of α-thalassemia Trait, Hb Bart hydrops, ATRx α-thalassemia, hemoglobin S/β-thalassemia, myelodysplasia subtype anemia, or with HbE homozygous beta gene mutation. Anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia, or any other hemolytic anemias. Bleeding disorders manifested by frequent bleeding episodes. Undergone episodes of hemolysis not related to α-thalassemia within the 8 weeks prior to randomization. - Reproductive Status: Women who are pregnant, plan to get pregnant during the study, or who are breastfeeding. - Prior/Concomitant Therapy: Prior exposure to gene therapy to treat α-thalassemia. Undergone hematopoietic stem cell transplantation (HSCT)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Adult cohorts, Primary endpoints: - TD: Achievement of ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 12 weeks during Weeks 13-48 compared to the 12-week interval immediately prior to the date of first dose.
2. Adult cohorts, Primary endpoints: - NTD: Achievement of an increase from baseline of ≥ 1.0 g/dL in mean hemoglobin values over the continuous 12-week interval from Week 13 to Week 24 in the absence of RBC transfusion.
3. Adolescent cohorts, Primary endpoints: - Dose-limiting toxicities (DLTs) defined as observance of ≥ Grade 3-related hemolytic crises or ≥ Grade 3-related event outside of the known safety profile occurring within the 21 days from their first dose of study therapy. - PK parameters - Frequency, severity, and seriousness of AEs

Investigational products

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

Test 2

Placebo 1

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 11

Locations

2 EU/EEA countries · 9 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 41 files

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

Application history

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