ETUVETIDIGENE AUTOTEMCEL for Wiskott-Aldrich syndrome

Inclusion criteria

• {"criterion_text":"- Patients enrolled in the phase I/II studies and treated by a single infusion of autologous CD34+ cells transduced with the w1.6_hWASP_WPRE (VSVg) lentiviral vector for WAS conducted in France and United Kingdom (GTG002.07 and GTG003. 08)\n- Parents, guardians or patient signed informed consent."}

Exclusion criteria

• {"criterion_text":"- Parents, guardians, patients unwilling to return for the follow up study period."}

Primary endpoints

• {"endpoint_text":"- To evaluate the incidence and type of SAEs and more specifically the incidence and nature of delayed events such as malignancies, hematologic, autoimmune events, mortality continuously over the 13 years duration of the post gene therapy follow up study.","definition_or_measurement_approach":"Continuous monitoring of Serious Adverse Events (SAEs) over a 13-year post-gene-therapy follow-up period; assessment of incidence and types of delayed events including malignancies, hematologic and autoimmune events, and mortality."}
• {"endpoint_text":"- To evaluate the safety of the gene therapy procedure for gene transfer analysis at yearly post gene therapy visits: lentiviral integration sites in different cell subpopulation, quantification of VCN (vector copy numbers) on sorted cell population by real time by q-PCR. At 11, 12, 13, 14 and 15 years post gene therapy time points, lentiviral integration sites will be assessed only in case of AESI occurrence.","definition_or_measurement_approach":"Yearly assessment of lentiviral integration sites in different cell subpopulations and quantification of Vector Copy Number (VCN) on sorted cell populations by real-time qPCR; integration site analysis at years 11-15 only if an Adverse Event of Special Interest (AESI) occurs."}
• {"endpoint_text":"- To evaluate the safety of the gene therapy procedure for replication competent lentivirus (RCL) at yearly post gene therapy visits. At 11, 12, 13, 14 and 15 years post gene therapy time points, RCL will be assessed only in case of AESI occurrence.","definition_or_measurement_approach":"Yearly testing for replication competent lentivirus (RCL) during post-gene-therapy visits; RCL testing at years 11-15 only if AESI occurs."}
• {"endpoint_text":"- To evaluate the clinical status of patients at 3, 4, 5, 6, 7, 8, 9 and 10 years post gene therapy visits: weight, and complete clinical exam .","definition_or_measurement_approach":"Clinical assessments at years 3-10 post-gene-therapy including weight measurement and complete clinical examination."}
• {"endpoint_text":"- To evaluate the evolution of the key medical events related to the WAS at 3, 4, 5, 6, 7, 8, 9 and 10 years post gene therapy visits: eczema status, infections, bleeding symptoms, autoimmune manifestations.","definition_or_measurement_approach":"Annual assessment (years 3-10) of WAS-related medical events: eczema status, infections, bleeding symptoms, and autoimmune manifestations."}
• {"endpoint_text":"- To evaluate the haematological reconstitution of the patient at 3, 4, 5, 6, 7, 8, 9 and 10 years post gene therapy visits: CBC including platelet count and size.","definition_or_measurement_approach":"Complete blood count (CBC) including platelet count and size at years 3-10 post-gene-therapy to assess hematological reconstitution."}
• {"endpoint_text":"- To evaluate the reconstitution of cell mediated and humoral immunity of the patient: o at 3, 4, 5, 6, 7, 8, 9 and 10 years post gene therapy visits: immunophenotyping panel (Lymphocytes subset including Wasp protein expression), restoration of antibody production (IgA, IgM, IgG, IgE), whole blood lymphocytes proliferation assays, humoral response to antigen (CD3 stimulation). o at 3, 4 and 5 years post gene therapy visits: humoral response to antigen (PHA, candida).","definition_or_measurement_approach":"Immunological assessments including immunophenotyping (lymphocyte subsets including Wasp protein expression), antibody quantification (IgA, IgM, IgG, IgE), lymphocyte proliferation assays, and humoral responses to antigens (CD3 stimulation); additional humoral response testing (PHA, Candida) at years 3-5."}

Secondary endpoints

• {"endpoint_text":"- To evaluate the evolution of the need for associated treatments at yearly post gene therapy visits (Immunoglobulins, antibacterial, antifungal and antiviral drugs, transfusions).","definition_or_measurement_approach":"Annual assessment of requirement for concomitant/associated treatments such as immunoglobulins, antibacterial, antifungal and antiviral drugs, and transfusions."}
• {"endpoint_text":"- To evaluate the representation of TCR families by PCR, TREC (TCR excision circle) and TCR V beta panel at 3, 4 and 5 years post gene therapy.","definition_or_measurement_approach":"Assessment at years 3, 4 and 5 of T-cell receptor (TCR) family representation by PCR, measurement of TREC (TCR excision circles), and TCR V-beta panel analysis."}
• {"endpoint_text":"- To evaluate the bone marrow integrity at 3, 4 and 5 years post gene therapy by performing a bone marrow aspiration (optional).","definition_or_measurement_approach":"Optional bone marrow aspiration performed at years 3, 4 and 5 to evaluate bone marrow integrity."}

France

Earliest CTIS Part Ii Submission Date

10-07-2024

Latest Decision Or Authorization Date

25-07-2024

Processing Time Days

15

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Genethon

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Ax-Pharma","duties_or_roles":"sponsorDuties code 8","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Eurofins Biomnis","duties_or_roles":"sponsorDuties code 4","organisation_type":"Laboratory/Research/Testing facility"}