X-linked Chronic Granulomatous Disease MedDRA version: 14.1 Level: PT Classification code 10008906 Term: Chronic granulomatous disease System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Suspension of autologous CD34+cells transduced with the G1XCGD viral vector
Product Code: G1XCGD transduced CD34+ cells
Pharmaceutical Form: Suspension for injection
Other descriptive na
Sponsors
GENETHON
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: -Male X-CGD patients > 23 months of age -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 severe infection and/or inflammatory complications requiring hospitalisation despite conventional therapy -No HLA-matched donor available after 3 months search -No co-infection with Human Immunodeficiency Virus (HIV) or hepatitis B virus (HBsAg 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: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
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 -Administration of gammainterferon 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: -Evaluation of safety -Evaluation of 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 augmented immunity against bacterial and fungal infection -Transduction of CD34+ haematopoietic cells from X-CGD patients by ex vivo lentivirus-mediated gene transfer -Evaluation of engraftment kinetics and stability ;Primary end point(s): -Safety of the procedure as measured by the incidence of adverse events -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: - The assessment of the safety of G1XCGD by the measurement of the safety parameters, e.g. adverse events. This will include clinical adverse events, as well as any clinically significant laboratory abnormality which will have to be reported as an AE. Overall incidence of adverse events will be evaluated for the study as a whole. Similarly the incidence of serious adverse events will be monitored. - The determination of the efficacy of G1XCGD. It will be evaluated by the measurementof the percentage of expression in granulocytes at month 12 by DHR test. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): As a secondary efficacy endpoint, the evolution of the nutritional status, the growth and the development will be evaluated by the regular clinical examination during the study visit. Similarly, the evolution of the severe infection and inflammation will be evaluated by the clinical exam but also by the imaging and the laboratory results. For the immmunological reconstitution, the restoration of the neutrophil functionality and immunity will be measured by the NADPH oxidase activity (NBC and DHR) and the percentage of transduced CD34+ haematopoietic cells infused and of blood cells at month 1, 2, 3, 6, 9, 12, 18 and 24). ;Timepoint(s) of evaluation of this end point: As a secondary efficacy endpoint, the evolution of the nutritional status, the growth and the development will be evaluated by the regular clinical examination during the study visit. Similarly, the evolution of the severe infection and inflammation will be evaluated by the clinical exam but also by the imaging and the laboratory results. For the immmunological reconstitution, the restoration of the neutrophil functionality and immunity will be measured by the NADPH oxidase activity (NBC and DHR) and the percentage of transduced CD34+ haematopoietic cells infused and of blood cells at month 1, 2, 3, 6, 9, 12, 18 and 24 to be validated with the Investigators). | — |
Countries
France, Germany, Switzerland, United Kingdom
Contacts
Public ContactMalika SOUQUIERES
GENETHON
Outcome results
None listed