A phase I/II, non randomized, monocentric open-label study of autologous CD34+ cells transduced with the G1XCGD lentiviral vector in patients with X-Linked Chronic Granulomatous Disease

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] - Immune System Diseases [C20]

Trial duration

19 Apr 2016 → 17 Oct 2025

Decision date (initial)

2024-07-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-512790-27-00

EudraCT number

2014-002222-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic

Evaluation of safety and efficacy by biochemical and functional reconstitution in progeny of engrafted cells and stability at 12 months.

Secondary objectives 3

1. Clinical efficacy and longitudinal evaluation of clinical effect in terms of improved immunity against bacterial and fungal infection.
2. Transduction of CD34+ haematopoietic stem cells from X-CGD patients by ex vivo lentivirus-mediated gene transfer.
3. Evaluation of engraftment kinetics and stability of gene modified CD34+ cells.

Conditions and MedDRA coding

Treatment of X-linked Chronic Granulomatous Disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. a. Male X-CGD patients >23 months of age. Youngest patients (>1 month and ≤ 23 months) may be enrolled at physician’s appreciation; in this case mobilization of peripheral HSC may be replaced by two bone marrow harvests.
2. b. Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or reduction > 70% of the biochemical activity of the NAHPD-oxidase.
3. c. At least one ongoing or resistant or at high risk of relapse severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy.
4. d. No HLA-matched donor available after 3 months search, unless the risk of waiting for a potential match or for performing an allogeneic transplant is considered unacceptable.
5. e. No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBs Ag positive) or hepatitis C virus (anti-HCV Ab positive).
6. f. written informed consent for adult patient.
7. g. Parental/guardian and where appropriate child’s signed consent/assent.

Exclusion criteria 9

1. a. 10/10 HLA identical (A, B, C, DR, DQ) family or unrelated.
2. b. Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy).
3. c. Contraindication for administration of conditioning medication and any component of the Investigational Medicinal Product (IMP) preparation.
4. d. Administration of gamma interferon within 30 days before the infusion of transduced autologous CD34+ cells.
5. e. Tested positive (definitive) for the presence of multiple types (2 or more) of anti-platelet antibodies
6. f. Tested positive (definitive) for the presence of anti-HLA (Class I & II) antibodies.
7. g. Participation in another experimental therapeutic protocol within 6 months prior to baseline and during the study period.
8. h. Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful completion of the study.
9. i. Patient/Parent/Guardian unable or unwilling to comply with the protocol requirements

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Safety as measured by the incidence of adverse events due either to the conditioning regimen, the IMP or to the procedure itself.
2. Efficacy as measured by the restoration and stability over time of the NADPH functioning granulocytes assessed by a DHR test (≥ 5% of expressing cells at 12 months).

Secondary endpoints 3

1. Normalisation of nutritional status, growth, development (as measured by clinical evaluation), clearing of the pre-existing severe infection and/or chronic inflammatory lesions which recommended patient’s inclusion
2. Percentage of transduced CD34+ haematopoietic stem cell at one year and percentage of transduced mature blood cells over time
3. Immunological reconstitution as measured by evidence of restored neutrophil functionality and immunity against bacterial and fungal infections over time.

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 16 files

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

Application history

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