Chronic Granulomatous Disease (CGD) is a rare inherited disorder (1/250,000) of the phagocytes characterized by the inability of phagocytes (monocytes and neutrophils) to produce reactive oxygen species (ROS) in response to a stimulus, due to the absence of NADPH oxidase activity. Affected patients present an elevated susceptibility to bacterial and fungal infections, as well as an excessive inflammatory response that leads to granuloma formation.
Conditions
Interventions
Product Name: Autologous CD34+ cells transduced with the G1XCGD lentiviral vector
Pharmaceutical Form: Suspension for injection
Other descriptive name: AUTOLOGOUS CD34+ CELLS TRANSDUCED EX-VIVO WITH T
Sponsors
Genethon
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: -Male X-CGD patients >23 months of age. Youngest patients (>1 month and = 23 months) may be enrolled at physician’s appreciation -Molecular diagnosis confirmed by DNA sequencing and supported by laboratory evidence for absent or reduction > 70% of the biochemical activity of the NAHPD-oxidase -At least one ongoing or resistant or at high risk of relapse severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy -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 -No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBs Ag positive) or hepatitis C virus (HCV RNA positive) -Written informed consent for adult patient -Parental/guardian and where appropriate child’s signed consent/assent Are the trial subjects under 18? yes Number of subjects for this age range: 4 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: -10/10 HLA identical (A, B, C, DR, DQ) family or unrelated or cord blood donor unless there is deemed to be an unacceptable risk associated with an allogeneic procedure -Contraindication for leukapheresis (anaemia Hb <8g/dl, cardiovascular instability, severe coagulopathy) -Contraindication for administration of conditioning medication and any component of the Investigational Medicinal Product (IMP) preparation -Administration of gamma interferon within 30 days before the infusion of transduced autologous CD34+ cells -Participation in another experimental therapeutic protocol within 6 months prior to baseline and during the study period -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 -Patient/Parent/Guardian unable or unwilling to comply with the protocol requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this phase I/II clinical trial is to assess the safety and the possible efficacy (by biochemical and functional reconstitution in progeny of engrafted cells and stability at 12 months) of autologous CD34+ cells transduced with the G1XCGD lentiviral vector, containing the human gp91phox (CYBB) gene, injected intravenously in patients adults or minors suffering from X-Linked Chronic Granulomatous Disease. ;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 ;Primary end point(s): Safety as measured by the incidence of adverse events due either to the conditioning regimen 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). ;Timepoint(s) of evaluation of this end point: For safety end point: throughout the study For efficacy: at 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 -Percentage of transduced CD34+ haematopoietic stem cell at one year and percentage of transduced mature blood cells over time (at month 1, 2,3, 6, 9, 12, 18 and 24 months) -Immunological reconstitution as measured by evidence of restored neutrophil functionality and immunity against bacterial and fungal infections over time. ;Timepoint(s) of evaluation of this end point: at month 1, 2,3, 6, 9, 12, 18 and 24 months | — |
Countries
France
Contacts
Public ContactGéraldine Honnet
Genethon
Outcome results
None listed