Gene Therapy for Wiskott-Aldrich Syndrome (WAS)

NCT01347242 | Completed Phase 1 DMC

• 1 other identifier: GTG002.07
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

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.

Conditions

Wiskott-Aldrich Syndrome

Keywords

Wiskott-Aldrich Syndrome; Primary immune deficiency; ex vivo gene therapy; hematopoietic stem cells

Outcome Measures

Primary Outcomes (5)

• Improvement in the eczema status

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

  2 years

• 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

• 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

• 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

• 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 Outcomes (7)

• Occurrence and type of adverse events

  2 years

• Change in medical conditions

  2 years

• Safety of lentivirus gene transfer into Hematopoietic Stem Cells

  3, 6, 12, 24 months / 6, 12, 18, 24 months

• Improvement of microthrombocytopenia

  3, 6, 12, 24 months

• Decrease in the number and volume of platelets transfusions

  2 years

Study Arms (1)

study treatment

EXPERIMENTAL

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

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

Interventions

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

transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WAS gene

study treatment

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genethon: lead
• Great Ormond Street Hospital for Children NHS Foundation Trust: collaborator
• Institute of Child Health: collaborator

Study Sites (2)

Great Ormond Street Hospital

London, WC1N 1EH, United Kingdom

Location

Royal Free Hospital

London, WC1N 1EH, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 35075289 DERIVED

• 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.

  PMID: 28716862 DERIVED

MeSH Terms

Conditions

Wiskott-Aldrich Syndrome; Primary Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphopenia; Leukopenia; Cytopenia; Hemorrhagic Disorders; Leukocyte Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2011
• First Posted: May 4, 2011
• Study Start: March 1, 2011
• Primary Completion: November 13, 2019
• Study Completion: November 13, 2019
• Last Updated: June 3, 2021

Record last verified: 2019-11

Locations

GB (2)