Long Term Safety Follow up of Haematopoietic Stem Cell Gene Therapy for the Wiskott Aldrich Syndrome

Study Overview
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Brief Summary
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An open follow up study of patients enrolled in the Phase 1/2 clinical trial of haematopoietic stem cell gene therapy for the Wiskott-Aldrich Syndrome and treated with autologous CD34+ cells transduced with the w1.6_hWASP_WPRE (VSVg) lentiviral vector.

Official Title
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Long Term Safety Follow up of Patients Enrolled in the Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott Aldrich Syndrome (GTG002-07 and GTG003-08).

Conditions
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Wiskott-Aldrich Syndrome

Intervention / Treatment
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* Genetic: Autologous CD34+ cells transduced with WASP lentiviral vector


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients enrolled in the initial phase I/II WAS conducted in France and United Kingdom (GTG002.07 and GTG003.08). Parents, guardians or patient signed informed consent, guardians or patient signed informed consent Exclusion Criteria: • Parents, guardians, patients unwilling to return for the follow up study period.
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: Autologous CD34+ cells transduced with WASP lentiviral vector|Follow up of ex vivo gene therapy transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WASP gene|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and type of SAEs | Incidence and nature of delayed events such as malignancies, hematologic, autoimmune events, mortality | yearly from 3 years to 15 years | 
| Lentiviral integration sites | Presence of lentiviral integration sites in different cells sub-populations | yearly from 3 years to 15 years (from 11 to 15 yearly time points, only in case of Advers Events of Special Interest) | 
| Vector copy numbers | Quantification of vector copy numbers on sorted cells population by q-PCR | yearly from 3 years to 15 years (from 11 to 15 yearly time points, only in case of Advers Events of Special Interest) | 
| Replication competent lentivirus (RCL) | Presence of RCL | yearly from 3 years to 15 years (from 11 to 15 yearly time points, only in case of Advers Events of Special Interest) | 
| Change in medical conditions | Weight and complete clinical exam | yearly from 3 years to 10 years | 
| Key medical events related to WAS | Eczema status, infections, bleeding symptoms, autoimmune manifestation | yearly from 3 years to 10 years | 
| Hematological reconstitution | CBC including platelets count and size | yearly from 3 years to 10 years | 
| Reconstitution of cell mediated and humoral immunity | Immunophenotyping panel, whole blood lymphocytes proliferation assays, restoration of antibody production, humoral response to antigene | yearly from 3 years to 10 years (from 3 years to 5 years for PHA and candida ) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for associated treatments | Immunoglobulins, antibacterial, antifungal, antiviral drugs, transfusions | yearly from 3 years to 15 years | 
| Representation of TCR families | Representation of TCR families by PCR TREC (TCR excision circle) and TCR V beta panel | yearly from 3 years to 5 years | 
| Bone marrow content | Numbers and type of cells in bone marrow | yearly from 3 years to 5 years (optional) |