Gene Therapy for Wiskott-Aldrich Syndrome (WAS)

Study Overview
=================
Brief Summary
-----------------
This is a phase I/II study to evaluate the safety and efficacy of Hematopoietic Stem Cell genetherapy for the Wiskott-Aldrich Syndrome.

Detailed Description
-----------------
This clinical trial is an ex vivo gene therapy trial. The investigational product corresponds to autologous CD34+ cells transduced with a lentiviral vector harboring the human WASP gene.

Official Title
-----------------
Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome

Conditions
-----------------
Wiskott-Aldrich Syndrome

Intervention / Treatment
-----------------
* Genetic: Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: males of all ages severe WAS (clinical score 3-5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry molecular confirmation by WAS gene DNA sequencing lack of HLA-genotypically identical bone marrow or of a 10/10 antigen HLA-matched unrelated donor or cord blood after 3 month search parental, guardian, patient signed informed consent/assent willing to return for follow-up only for patients who have received previous allogenic hematopoietic stem cell transplant: failed allogenic hematopoietic stem cell transplant contraindication to repeat transplantation Exclusion Criteria: patient with HLA-genotypically identical bone marrow patient with 10/10 antigen HLA-matched unrelated donor or cord blood contraindication to leukapheresis contraindication to bone marrow harvest contraindication to administration of conditioning medication HIV positive patient
Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: study treatment<br>autologous CD34 positive cells transduced with a lentiviral vector containing the human WAS gene | Genetic: Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene<br>* transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WAS gene<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in the eczema status | Improvement in the eczema status as compared with the baseline status at study entry on clinical evaluation | 2 years | 
| Reduction in the frequency and severity of infection episodes | Reduction in the frequency and severity of infection episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry | 2 years | 
| Reduction in the frequency and severity of bruising and bleeding episodes | Reduction in the frequency and severity of bruising and bleeding episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry | 2 years | 
| Reduction in the frequency and severity of autoimmune disorders | Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry | 2 years | 
| Reduction in the number of disease related days of hospitalization | Reduction in the number of disease related days of hospitalization as compared with the patient's historical data collected over the 2 years prior to study entry | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence and type of adverse events | Occurrence and type of adverse events reported during the course of the study | 2 years | 
| Change in medical conditions | Assessment of weight, vital signs, ECG and laboratory exams during the course of the study | 2 years | 
| Safety of lentivirus gene transfer into Hematopoietic Stem Cells | Detection of replication competent lentivirus (RCL) and lentivirus integration sites analysis | 3, 6, 12, 24 months / 6, 12, 18, 24 months | 
| Improvement of microthrombocytopenia | Improvement of microthrombocytopenia as compared with the baseline evaluation at study entry | 3, 6, 12, 24 months | 
| Decrease in the number and volume of platelets transfusions | Decrease in the number and volume of platelets transfusions as compared with patient's historical data collected over the 2 years prior to study entry | 2 years | 
| Evidence of sustained engrafment of WASP-expressing transduced cells | Quantification of vector copy numbers and detection of vector-derived WASP expression | 6 weeks, 1, 3, 6, 9, 12, 18 & 24 months | 
| Reconstitution of humoral and cell mediated immunity | Reconstitution of humoral and cell mediated immunity as compared with the baseline evaluation at study entry | 9, 12, 18 & 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Wiskott-Aldrich Syndrome, Primary immune deficiency, ex vivo gene therapy, hematopoietic stem cells