Long-term follow-up of the WAS gene therapy study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genethon

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male

Therapeutic area

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

Trial duration

29 Oct 2014 → ongoing

Decision date (initial)

2024-07-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-512680-31-00

EudraCT number

2014-000274-20

ClinicalTrials.gov

NCT02333760

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety

Long term follow up of WAS patients who received an autologous transplantation with CD34+ cells transduced with the w1.6_hWASP_WPRE (VSVg) lentiviral vector.

Conditions and MedDRA coding

Treatment of Wiskott-Aldrich Syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Patients enrolled in the phase I/II studies and treated by a single infusion of autologous CD34+ cells transduced with the w1.6_hWASP_WPRE (VSVg) lentiviral vector for WAS conducted in France and United Kingdom (GTG002.07 and GTG003. 08)
2. Parents, guardians or patient signed informed consent.

Exclusion criteria 1

1. Parents, guardians, patients unwilling to return for the follow up study period.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. To evaluate the incidence and type of SAEs and more specifically the incidence and nature of delayed events such as malignancies, hematologic, autoimmune events, mortality continuously over the 13 years duration of the post gene therapy follow up study.
2. To evaluate the safety of the gene therapy procedure for gene transfer analysis at yearly post gene therapy visits: lentiviral integration sites in different cell subpopulation, quantification of VCN (vector copy numbers) on sorted cell population by real time by q-PCR. At 11, 12, 13, 14 and 15 years post gene therapy time points, lentiviral integration sites will be assessed only in case of AESI occurrence.
3. To evaluate the safety of the gene therapy procedure for replication competent lentivirus (RCL) at yearly post gene therapy visits. At 11, 12, 13, 14 and 15 years post gene therapy time points, RCL will be assessed only in case of AESI occurrence.
4. To evaluate the clinical status of patients at 3, 4, 5, 6, 7, 8, 9 and 10 years post gene therapy visits: weight, and complete clinical exam .
5. To evaluate the evolution of the key medical events related to the WAS at 3, 4, 5, 6, 7, 8, 9 and 10 years post gene therapy visits: eczema status, infections, bleeding symptoms, autoimmune manifestations.
6. To evaluate the haematological reconstitution of the patient at 3, 4, 5, 6, 7, 8, 9 and 10 years post gene therapy visits: CBC including platelet count and size.
7. To evaluate the reconstitution of cell mediated and humoral immunity of the patient: o at 3, 4, 5, 6, 7, 8, 9 and 10 years post gene therapy visits: immunophenotyping panel (Lymphocytes subset including Wasp protein expression), restoration of antibody production (IgA, IgM, IgG, IgE), whole blood lymphocytes proliferation assays, humoral response to antigen (CD3 stimulation). o at 3, 4 and 5 years post gene therapy visits: humoral response to antigen (PHA, candida).

Secondary endpoints 3

1. To evaluate the evolution of the need for associated treatments at yearly post gene therapy visits (Immunoglobulins, antibacterial, antifungal and antiviral drugs, transfusions).
2. To evaluate the representation of TCR families by PCR, TREC (TCR excision circle) and TCR V beta panel at 3, 4 and 5 years post gene therapy.
3. To evaluate the bone marrow integrity at 3, 4 and 5 years post gene therapy by performing a bone marrow aspiration (optional).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genethon

Sponsor organisation

Genethon

Address

1 Rue De L Internationale

City

Evry-Courcouronnes

Postcode

91000

Country

France

Scientific contact point

Organisation

Genethon

Contact name

Clinical Development Department

Public contact point

Organisation

Genethon

Contact name

Clinical Development Department

Third parties 2

Locations

1 EU/EEA country · 1 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 7 files

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

Application history

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