Gene Therapy for Wiskott-Aldrich Syndrome (WAS)

Phase 1

Completed

• Conditions: Wiskott-Aldrich Syndrome
• Interventions: Genetic: Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene

• Registration Number: NCT01347242
• Lead Sponsor: Genethon

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.

Study Timeline

• Study Start: 2011-03
• Study First Submitted: 2011-05-03
• Study First Submitted QC: 2011-05-03
• Study First Posted: 2011-05-04
• Status Verified: 2019-11
• Primary Completion: 2019-11-13
• Study Completion: 2019-11-13
• Last Update Submitted: 2021-05-31
• Last Update Posted: 2021-06-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 6

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
study treatment	Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene	autologous CD34 positive cells transduced with a lentiviral vector containing the human WAS gene

Primary Outcome Measures

Name	Time	Method
Reduction in the frequency and severity of bruising and bleeding episodes	2 years	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
Improvement in the eczema status	2 years	Improvement in the eczema status as compared with the baseline status at study entry on clinical evaluation
Reduction in the number of disease related days of hospitalization	2 years	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
Reduction in the frequency and severity of infection episodes	2 years	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
Reduction in the frequency and severity of autoimmune disorders	2 years	Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Royal Free Hospital; 🇬🇧 London, United Kingdom

Great Ormond Street Hospital; 🇬🇧 London, United Kingdom