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Gene Therapy for WAS

Primary Purpose

Wiskott-Aldrich Syndrome

Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene
Sponsored by
Genethon
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Wiskott-Aldrich Syndrome focused on measuring Wiskott-Aldrich Syndrome, Primary immune deficiency, ex vivo gene therapy, hematopoietic stem cells

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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 after 3 month search
  • lack of a 10/10 or 9/10 antigen HLA-matched unrelated donor after 3 month search
  • lack of a HLA-matched 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 or 9/10 antigen HLA-matched unrelated donor or with HLA-matched cord blood
  • contraindication to leukapheresis
  • contraindication to bone marrow harvest
  • contraindication to administration of conditioning medication
  • HIV positive patient

Sites / Locations

  • Hôpital Necker-Enfants Malades

Outcomes

Primary Outcome Measures

Improvement in the eczema status
Improvement in eczema status as compared with the baseline status at study entry on clinical evaluation
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
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
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
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

Secondary Outcome Measures

Occurrence and type of adverse events
Occurrence and type of adverse events reported during the course of the study
Change in medical conditions
Assessment of weight, vital signs, ECG and laboratory exams during the course of the study
Safety of lentivirus gene transfer into Hematopoietic Stem Cells
Detection of replication competent lentivirus (RCL) and lentivirus integration sites analysis
Improvement of microthrombocytopenia
Improvement of microthrombocytopenia as compared with the baseline evaluation at study entry
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
Evidence of sustained engraftment of WASP-expressing transduced cells
Quantification of vector copy numbers and detection of vector-derived WASP expression
Reconstitution of humoral and cell mediated immunity
Reconstitution of humoral and cell mediated immunity as compared with the baseline evaluation at study entry

Full Information

First Posted
May 3, 2011
Last Updated
May 18, 2018
Sponsor
Genethon
Collaborators
Hôpital Necker-Enfants Malades
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1. Study Identification

Unique Protocol Identification Number
NCT01347346
Brief Title
Gene Therapy for WAS
Official Title
Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
May 2011 (undefined)
Primary Completion Date
January 13, 2016 (Actual)
Study Completion Date
January 9, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genethon
Collaborators
Hôpital Necker-Enfants Malades

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wiskott-Aldrich Syndrome
Keywords
Wiskott-Aldrich Syndrome, Primary immune deficiency, ex vivo gene therapy, hematopoietic stem cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Genetic
Intervention Name(s)
Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene
Intervention Description
transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WAS gene
Primary Outcome Measure Information:
Title
Improvement in the eczema status
Description
Improvement in eczema status as compared with the baseline status at study entry on clinical evaluation
Time Frame
2 years
Title
Reduction in the frequency and severity of infection episodes
Description
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
Time Frame
2 years
Title
Reduction in the frequency and severity of bruising and bleeding episodes
Description
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
Time Frame
2 years
Title
Reduction in the frequency and severity of autoimmune disorders
Description
Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry
Time Frame
2 years
Title
Reduction in the number of disease related days of hospitalization
Description
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
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Occurrence and type of adverse events
Description
Occurrence and type of adverse events reported during the course of the study
Time Frame
2 years
Title
Change in medical conditions
Description
Assessment of weight, vital signs, ECG and laboratory exams during the course of the study
Time Frame
2 years
Title
Safety of lentivirus gene transfer into Hematopoietic Stem Cells
Description
Detection of replication competent lentivirus (RCL) and lentivirus integration sites analysis
Time Frame
3, 6, 12, 24 months / 6, 12, 18, 24 months
Title
Improvement of microthrombocytopenia
Description
Improvement of microthrombocytopenia as compared with the baseline evaluation at study entry
Time Frame
3, 6, 12, 24 months
Title
Decrease in the number and volume of platelets transfusions
Description
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
Time Frame
2 years
Title
Evidence of sustained engraftment of WASP-expressing transduced cells
Description
Quantification of vector copy numbers and detection of vector-derived WASP expression
Time Frame
6 weeks, 1, 3, 6, 9, 12, 18 & 24 months
Title
Reconstitution of humoral and cell mediated immunity
Description
Reconstitution of humoral and cell mediated immunity as compared with the baseline evaluation at study entry
Time Frame
9, 12, 18 & 24 months

10. Eligibility

Sex
Male
Accepts Healthy Volunteers
No
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 after 3 month search lack of a 10/10 or 9/10 antigen HLA-matched unrelated donor after 3 month search lack of a HLA-matched 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 or 9/10 antigen HLA-matched unrelated donor or with HLA-matched cord blood contraindication to leukapheresis contraindication to bone marrow harvest contraindication to administration of conditioning medication HIV positive patient
Facility Information:
Facility Name
Hôpital Necker-Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
35075289
Citation
Magnani A, Semeraro M, Adam F, Booth C, Dupre L, Morris EC, Gabrion A, Roudaut C, Borgel D, Toubert A, Clave E, Abdo C, Gorochov G, Petermann R, Guiot M, Miyara M, Moshous D, Magrin E, Denis A, Suarez F, Lagresle C, Roche AM, Everett J, Trinquand A, Guisset M, Bayford JX, Hacein-Bey-Abina S, Kauskot A, Elfeky R, Rivat C, Abbas S, Gaspar HB, Macintyre E, Picard C, Bushman FD, Galy A, Fischer A, Six E, Thrasher AJ, Cavazzana M. Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome. Nat Med. 2022 Jan;28(1):71-80. doi: 10.1038/s41591-021-01641-x. Epub 2022 Jan 24. Erratum In: Nat Med. 2022 Oct;28(10):2217.
Results Reference
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Gene Therapy for WAS

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