A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Transfusion-Dependent β-Thalassemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vertex Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

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

Trial duration

16 May 2022 → ongoing

Decision date (initial)

2024-11-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-513349-35-00

EudraCT number

2021-002172-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Evaluate the efficacy of a single dose of autologous CRISPR-Cas9 modified
CD34+ human hematopoietic stem and progenitor cells (hHSPCs) (CTX001) in pediatric subjects with transfusion-dependent β-thalassemia (TDT)

Secondary objectives 4

1. Evaluate the safety and tolerability of a single dose of CTX001
2. Quantify percentage of edited alleles in peripheral blood and CD34+ cells of the bone marrow
3. Assess the production of fetal hemoglobin (HbF) post-CTX001 infusion
4. Assess the effects of infusion of CTX001 on disease-specific events and clinical status

Conditions and MedDRA coding

Transfusion-Dependent-Thalassemia

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002730-PIP01-19

Plan to share IPD

No

IPD plan description

Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Diagnosis of TDT as defined by: a. Documented homozygous or compound heterozygous β-thalassemia including β-thalassemia/hemoglobin E (HbE). Participants can be enrolled based on historical data, but a confirmation of the genotype using the study central laboratory will be required before busulfan conditioning. b. History of at least 100 mL/kilograms (kg)/year of packed RBC transfusions in the prior 24 months before signing of consent (or the last rescreening for patients going through repeat screening) or, for participants initiating transfusion therapy <24 months before signing of consent, requirement for packed RBC transfusion at least every 3 to 4 weeks for ≥6 months.
2. Eligible for autologous stem cell transplant as per investigator's judgment.

Exclusion criteria 6

1. A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor is available per investigator's judgement
2. Prior hematopoietic stem cell transplant (HSCT)
3. Participants with associated α-thalassemia and >1 alpha deletion, or alpha multiplications
4. Participants with sickle cell β-thalassemia variant
5. Clinically significant and active bacterial, viral, fungal, or parasitic infection as determined by the investigator
6. Other protocol defined Inclusion/Exclusion criteria may apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects who achieve TI12. A subject will be considered to have achieved TI12 if he/she has maintained weighted average Hb ≥9 g/dL without RBC transfusions for at least 12 consecutive months any time after CTX001 infusion. The evaluation of TI12 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management.

Secondary endpoints 9

1. Proportion of Participants Achieving at Least 95 Percent (%), 90%, 85%, 75% and 50% Reduction in Annualized Transfusions
2. Relative Reduction in Annualized Volume of RBC Transfusions
3. Transfusion Free Duration for Participants who Achieve TI12
4. Proportion of Alleles With Intended Genetic Modification Present in Peripheral Blood Over Time
5. Proportion of Alleles With Intended Genetic Modification Present in CD34+ Cells of the Bone Marrow Over Time
6. HbF concentration (pre-transfusion) over time
7. Total hemoglobin concentration (pre-transfusion) over time.
8. Safety and tolerability of CTX001 based on adverse events (AEs), clinical laboratory values, vital signs, neutrophil engraftment, platelet engraftment, transplant-related mortality (TRM), and all-cause mortality
9. Proportion of subjects who achieve TI6. A subject will be considered to have achieved TI6 if he/she has maintained weighted average Hb ≥9 g/dL without RBC transfusions for at least 6 consecutive months any time after CTX001 infusion. The evaluation of TI6 starts 60 days after last RBC transfusion for post-transplant support or TDT disease management.

Investigational products

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

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vertex Pharmaceuticals Inc.

Sponsor organisation

Vertex Pharmaceuticals Inc.

Address

50 Northern Avenue

City

Boston

Postcode

02210-1862

Country

United States

Scientific contact point

Organisation

Vertex Pharmaceuticals Inc.

Contact name

Clinical Trials and Medical Info

Public contact point

Organisation

Vertex Pharmaceuticals Inc.

Contact name

Clinical Trials and Medical Info

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 18 files

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

Application history

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