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

Phase 1

Recruiting

• Conditions: Treatment of X-linked Chronic Granulomatous Disease; MedDRA version: 20.0Level: PTClassification code: 10008906Term: Chronic granulomatous disease Class: 100000004850; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: CTIS2024-512790-27-00
• Lead Sponsor: Genethon

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-02
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Male
• Target Recruitment: 5

Inclusion Criteria

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., 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., c. At least one ongoing or resistant or at high risk of relapse severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy., 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., e. No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBs Ag positive) or hepatitis C virus (anti-HCV Ab positive)., f. written informed consent for adult patient., g. Parental/guardian and where appropriate child’s signed consent/assent.

Exclusion Criteria

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluation of safety and efficacy by biochemical and functional reconstitution in progeny of engrafted cells and stability at 12 months.;Secondary Objective: Clinical efficacy and longitudinal evaluation of clinical effect in terms of improved immunity against bacterial and fungal infection., Transduction of CD34+ haematopoietic stem cells from X-CGD patients by ex vivo lentivirus-mediated gene transfer., Evaluation of engraftment kinetics and stability of gene modified CD34+ cells.;Primary end point(s): Safety as measured by the incidence of adverse events due either to the conditioning regimen, the IMP or to the procedure itself., 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 Outcome Measures

Name	Time	Method
Secondary end point(s):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;Secondary end point(s):Percentage of transduced CD34+ haematopoietic stem cell at one year and percentage of transduced mature blood cells over time;Secondary end point(s):Immunological reconstitution as measured by evidence of restored neutrophil functionality and immunity against bacterial and fungal infections over time.