Gene Therapy for WAS

NCT01347346 | Completed Phase 1 DMC

• 2 other identifiers: GTG003.082009-011152-22
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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 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

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

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genethon: lead
• Hôpital Necker-Enfants Malades: collaborator

Study Sites (1)

Hôpital Necker-Enfants Malades

Paris, 75015, France

Location

Related Publications (1)

• 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

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: NON RANDOMIZED
• 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: May 1, 2011
• Primary Completion: January 13, 2016
• Study Completion: January 9, 2017
• Last Updated: May 22, 2018

Record last verified: 2018-05

Locations

FR (1)