Clinical trial NCT01347242: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Wiskott-Aldrich Syndrome
Keywords: Wiskott-Aldrich Syndrome
Primary immune deficiency
ex vivo gene therapy
hematopoietic stem cells
Lead sponsor: Genethon
Sponsor class: OTHER
Collaborators: name: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Institute of Child Health
First posted: 2011-05-04
Enrollment: 6
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Improvement in the eczema status
timeFrame: 2 years
measure: Reduction in the frequency and severity of infection episodes
timeFrame: 2 years
measure: Reduction in the frequency and severity of bruising and bleeding episodes
timeFrame: 2 years
measure: Reduction in the frequency and severity of autoimmune disorders
timeFrame: 2 years
measure: Reduction in the number of disease related days of hospitalization
timeFrame: 2 years
Secondary outcomes:
measure: Occurrence and type of adverse events
timeFrame: 2 years
measure: Change in medical conditions
timeFrame: 2 years
measure: Safety of lentivirus gene transfer into Hematopoietic Stem Cells
timeFrame: 3, 6, 12, 24 months / 6, 12, 18, 24 months
measure: Improvement of microthrombocytopenia
timeFrame: 3, 6, 12, 24 months
measure: Decrease in the number and volume of platelets transfusions
timeFrame: 2 years
measure: Evidence of sustained engrafment of WASP-expressing transduced cells
timeFrame: 6 weeks, 1, 3, 6, 9, 12, 18 & 24 months
measure: Reconstitution of humoral and cell mediated immunity
timeFrame: 9, 12, 18 & 24 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
References:
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.
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.