Gene Therapy for Wiskott-Aldrich Syndrome (WAS)

Wiskott-Aldrich Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01347242
• Other study ID #: GTG002.07
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2011
• Est. completion date: November 13, 2019

Study information

• Verified date: November 2019
• Source: Genethon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: November 13, 2019
• Est. primary completion date: November 13, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Syndrome
• Wiskott-Aldrich Syndrome

Intervention

Genetic:
• Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene
transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WAS gene

Locations

Country	Name	City	State
United Kingdom	Great Ormond Street Hospital	London
United Kingdom	Royal Free Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
Genethon	Great Ormond Street Hospital for Children NHS Foundation Trust, Institute of Child Health

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in the eczema status	Improvement in the eczema status as compared with the baseline status at study entry on clinical evaluation	2 years
Primary	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
Primary	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
Primary	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
Primary	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	Occurrence and type of adverse events	Occurrence and type of adverse events reported during the course of the study	2 years
Secondary	Change in medical conditions	Assessment of weight, vital signs, ECG and laboratory exams during the course of the study	2 years
Secondary	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
Secondary	Improvement of microthrombocytopenia	Improvement of microthrombocytopenia as compared with the baseline evaluation at study entry	3, 6, 12, 24 months
Secondary	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
Secondary	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
Secondary	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