A Phase 3 Study to Evaluate the Safety and Efficacy of a Single Dose of CTX001 in Pediatric Subjects With Severe Sickle Cell Disease

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

20 Jul 2022 → ongoing

Decision date (initial)

2024-11-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-513978-22-00

EudraCT number

2021-002173-26

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 severe sickle cell disease (SCD)

Secondary objectives 3

1. Evaluate the safety and tolerability of a single dose of CTX001
2. Assess the effects of infusion of CTX001 on disease-specific events and clinical status
3. Quantify gene editing efficiency

Conditions and MedDRA coding

Severe sickle cell disease (SCD)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002730-PIP02-19

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 4

1. Diagnosis of severe SCD as defined by: Documented SCD genotypes
2. History of at least two severe VOCs events per year for the previous two years prior to enrollment
3. Hydroxyurea (HU) failure unless HU intolerant
4. Eligible for autologous stem cell transplant as per investigators judgment

Exclusion criteria 4

1. A willing and healthy 10/10 human leukocyte antigen (HLA)-matched related donor
2. Prior hematopoietic stem cell transplant (HSCT)
3. Clinically significant and active bacterial, viral, fungal, or parasitic infection
4. Other protocol defined Inclusion/Exclusion criteria may apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects who do not have any severe vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12) after CTX001 infusion. The evaluation of VF12 starts 60 days after the last red blood cell (RBC) transfusion for post- transplant support or SCD disease management.

Secondary endpoints 21

1. 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.
2. Proportion of subjects free from inpatient hospitalization for severe VOCs for at least 12 months (HF12) after CTX001 infusion. The evaluation of HF12 starts 60 days after last RBC transfusion for post-transplant support or SCD disease management.
3. Relative reduction from baseline in annualized rate of severe VOCs up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
4. Duration of severe VOC free in subjects who have achieved VF12.
5. Relative reduction from baseline in annualized rate of inpatient hospitalizations for severe VOCs up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management.
6. Relative reduction from baseline in annualized duration of hospitalization for severe VOCs up to 24 months after CTX001 infusion. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management.
7. Proportion of subjects with sustained fetal hemoglobin (HbF) ≥20% at the time of analysis for at least 3 months, 6 months, or 12 months. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
8. Proportion of subjects with sustained HbF ≥30% at the time of analysis for at least 3 months, 6 months, or 12 months. The evaluation starts 60 days after last RBC transfusion for post-transplant support or SCD disease management
9. Time for subjects to reach HbF ≥20%
10. Time for subjects to reach HbF ≥30%
11. Relative reduction from baseline in annualized volume of RBC transfusions
12. HbF concentrations over time
13. Hemoglobin (Hb) concentrations over time
14. Change from baseline in reticulocyte count (percent reticulocytes and absolute reticulocyte count) over time
15. Change from baseline in indirect bilirubin over time
16. Change from baseline in haptoglobin over time
17. Time to first detectable haptoglobin post CTX001 infusion
18. Change from baseline in lactate dehydrogenase (LDH) over time
19. Time to first normalized LDH (defined as within normal limits per local laboratory) post CTX001 infusion.
20. Proportion of alleles with intended genetic modification present in peripheral blood over time
21. Proportion of alleles with intended genetic modification present in CD34+ cells of the bone marrow over time

Investigational products

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

Test 1

Auxiliary 2

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 23 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