Long Term Safety Follow up of Haematopoietic Stem Cell Gene Therapy for the Wiskott Aldrich Syndrome (WASFUP)

Long Term Safety Follow up of Patients Enrolled in the Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott Aldrich Syndrome (GTG002-07 and GTG003-08).

An open follow up study of patients enrolled in the Phase 1/2 clinical trial of haematopoietic stem cell gene therapy for the Wiskott-Aldrich Syndrome and treated with autologous CD34+ cells transduced with the w1.6_hWASP_WPRE (VSVg) lentiviral vector.

Study Overview

• Status: Active, not recruiting
• Conditions: Wiskott-Aldrich Syndrome
• Intervention / Treatment: Genetic: Autologous CD34+ cells transduced with WASP lentiviral vector

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France, 75743
    • Hopital Necker - Enfants Malades
• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • UCL Institute of Child Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Patients enrolled in the initial phase I/II WAS conducted in France and United Kingdom (GTG002.07 and GTG003.08).
• Parents, guardians or patient signed informed consent, guardians or patient signed informed consent

Exclusion Criteria:

• Parents, guardians, patients unwilling to return for the follow up study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and type of SAEs	Incidence and nature of delayed events such as malignancies, hematologic, autoimmune events, mortality	yearly from 3 years to 15 years
Lentiviral integration sites	Presence of lentiviral integration sites in different cells sub-populations	yearly from 3 years to 15 years (from 11 to 15 yearly time points, only in case of Advers Events of Special Interest)
Vector copy numbers	Quantification of vector copy numbers on sorted cells population by q-PCR	yearly from 3 years to 15 years (from 11 to 15 yearly time points, only in case of Advers Events of Special Interest)
Replication competent lentivirus (RCL)	Presence of RCL	yearly from 3 years to 15 years (from 11 to 15 yearly time points, only in case of Advers Events of Special Interest)
Change in medical conditions	Weight and complete clinical exam	yearly from 3 years to 10 years
Key medical events related to WAS	Eczema status, infections, bleeding symptoms, autoimmune manifestation	yearly from 3 years to 10 years
Hematological reconstitution	CBC including platelets count and size	yearly from 3 years to 10 years
Reconstitution of cell mediated and humoral immunity	Immunophenotyping panel, whole blood lymphocytes proliferation assays, restoration of antibody production, humoral response to antigene	yearly from 3 years to 10 years (from 3 years to 5 years for PHA and candida )

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for associated treatments	Immunoglobulins, antibacterial, antifungal, antiviral drugs, transfusions	yearly from 3 years to 15 years
Representation of TCR families	Representation of TCR families by PCR TREC (TCR excision circle) and TCR V beta panel	yearly from 3 years to 5 years
Bone marrow content	Numbers and type of cells in bone marrow	yearly from 3 years to 5 years (optional)

Collaborators and Investigators

• Sponsor: Genethon

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Anticipated): October 1, 2032
• Study Completion (Anticipated): October 1, 2032

Study Registration Dates

• First Submitted: October 28, 2014
• First Submitted That Met QC Criteria: January 5, 2015
• First Posted (Estimate): January 7, 2015

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 31, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immunologic Deficiency Syndromes; Immune System Diseases; Disease; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Leukopenia; Leukocyte Disorders; Primary Immunodeficiency Diseases; Lymphopenia; Syndrome; Wiskott-Aldrich Syndrome
• Other Study ID Numbers: GNT-WAS-03