A Phase 1/2 Open Label non randomized Study, multicentric, single arm evaluating the Safety and Efficacy of Gene Therapy of the severe combined immunodeficiency (SCID) caused by mutations in the human DCLRE1C gene (Artemis) by transplantation of a single dose of autologous CD34+ cells transduced ex vivo with the G2ARTE lentiviral vector expressing the DCLRE1C cDNA

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

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

Trial duration

19 Jul 2023 → ongoing

Decision date (initial)

2024-09-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

European Research Council

External identifiers

EU CT number

2024-513652-15-00

EudraCT number

2019-003555-11

ClinicalTrials.gov

NCT05071222

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

The primary objective of the study consists in assessing the initial safety and efficacy of treatment with ARTEGENE drug product, including the mobilization procedure, conditioning regimen and transplantation with ARTEGENE lentiviral vector gene modified autologous hematopoietic stem cells in in up to 5 Artemis deficient patients.

Secondary objectives 3

1. Study the clearing of ongoing infections present before the transplantation.
2. Study the evaluation of the functional performance of this novel lentiviral vector
3. Study the assessment of the long-term safety and efficacy of treatment with the ARTEGENE drug product

Conditions and MedDRA coding

Severe Combined Immuno-Deficiency (SCID) caused by biallelic mutations in the Artemis gene (DCLRE1C)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patient up to 47 months of age
2. SCID patients with confirmed biallelic mutations in the Artemis (DCLRE1C) gene even in the case of leaky forms characterised by a residual activity
3. Absence of an HLA genoidentical donor or without rapidly available HLA-compatible unrelated donor (within six weeks of diagnosis)
4. The patient can be treated by gene therapy without delay in case of life threatening infections compromising the short-term prognosis and for which the delay in finding a phenoidentical donor is incompatible with the patient's condition of health. Active life threatening infections are defined as: viral respiratory infection, CMV infection, adenovirus infection, disseminated BCGitis or other infections grade ≥ 4 according to CTCAE scale
5. Beneficiary of a social security scheme
6. Parental, guardian’s patient signed informed consent

Exclusion criteria 4

1. Unwillingness to return for follow-up during the first 2 years study and the long term follow-up
2. HIV-1 or 2 or HTLV1 infections.
3. Hypersensitivity to G-CSF, busulfan or fludarabine
4. Unable to tolerate general anesthesia and/or marrow harvest or peripheral blood stem cell collection (apheresis) or insertion of central venous catheter

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and efficacy of ARTEGENE drug product

Secondary endpoints 3

1. End of ongoing infection before the transplantation
2. Kinetics of immune reconstitution
3. Adverse event will be measured using CTCAE

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Marina CAVAZZANA, MD, PhD

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Marina CAVAZZANA, MD, PhD

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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