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Gene Therapy for Wiskott-Aldrich Syndrome (WAS)

Primary Purpose

Wiskott-Aldrich Syndrome

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene

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 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

Sites / Locations

Great Ormond Street Hospital
Royal Free Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

study treatment

Arm Description

autologous CD34 positive cells transduced with a lentiviral vector containing the human WAS gene

Outcomes

Primary Outcome Measures

Improvement in the eczema status

Improvement in the 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 engrafment 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

NCT ID

NCT01347242

First Posted

May 3, 2011

Last Updated

May 31, 2021

Sponsor

Genethon

Collaborators

Great Ormond Street Hospital for Children NHS Foundation Trust, Institute of Child Health

1. Study Identification

Unique Protocol Identification Number

NCT01347242

Brief Title

Gene Therapy for Wiskott-Aldrich Syndrome (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

November 2019

Overall Recruitment Status

Completed

Study Start Date

March 2011 (Actual)

Primary Completion Date

November 13, 2019 (Actual)

Study Completion Date

November 13, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genethon

Collaborators

Great Ormond Street Hospital for Children NHS Foundation Trust, Institute of Child Health

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

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

study treatment

Arm Type

Experimental

Arm Description

autologous CD34 positive cells transduced with a lentiviral vector containing the human WAS gene

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 the 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 engrafment 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

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

Facility Information:

Facility Name

Great Ormond Street Hospital

City

London

ZIP/Postal Code

WC1N 1EH

Country

United Kingdom

Facility Name

Royal Free Hospital

City

London

ZIP/Postal Code

WC1N 1EH

Country

United Kingdom

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

derived

PubMed Identifier

28716862

Citation

Morris EC, Fox T, Chakraverty R, Tendeiro R, Snell K, Rivat C, Grace S, Gilmour K, Workman S, Buckland K, Butler K, Chee R, Salama AD, Ibrahim H, Hara H, Duret C, Mavilio F, Male F, Bushman FD, Galy A, Burns SO, Gaspar HB, Thrasher AJ. Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult. Blood. 2017 Sep 14;130(11):1327-1335. doi: 10.1182/blood-2017-04-777136. Epub 2017 Jul 17.

Results Reference

derived

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Gene Therapy for Wiskott-Aldrich Syndrome (WAS)

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