Gene Therapy for Wiskott-Aldrich Syndrome

Safety of Reduced Conditioning Regimen

The absence of prolonged aplasia (defined as ANC \<0.5×10\^9/L \[\<500/μL\] at Day +60, with no evidence of BM recovery and requiring backup administration) was assumed as demonstrating the safety of the RIC regimen.

Time frame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)

Safety of Lentivirus Gene Transfer Into HSC

Safety and tolerability of lentiviral-transduced cell infusion. This will be evaluated on the basis of adverse events reporting and monitoring of the systemic reactions to cell infusion.

Time frame: after 48 hours after Telethon003 infusion

Sustained Engraftment of Genetically Corrected Haematopoietic Stem Cells in Peripheral Blood and/or in Bone Marrow

Engraftment is characterized by the presence of gene modified cells in the BM or PB compartments. The main indicator of gene correction is detection of the WAS LVV sequences in the HSPCs and their progeny. The VCN, which is the mean number of integrated copies of the vector sequences per cell genome, was measured using PCR-based methods in DNA samples extracted from BM and PB cell populations at various timepoints post-treatment. Adequate engraftment was defined as either ≥0.04 VCN/cell in BM CD34+ cells or ≥0.01 VCN/cell in PB CD3+ cells.

Time frame: at 1 year after Telethon003 infusion

Presence of Detectable Vector-derived WASP

The percentage of subjects who present the proportion of PB cells expressing WASP was assessed by flow cytometry analysis.

Time frame: Median duration: 11.1 years (range: 8.01 -13.3 years)

Improved T-cell Functions

Improvement in in vitro T-cell proliferation was assessed upon stimulation with 3 doses of anti-immobilized CD3 (CD3i) monoclonal antibodies ≥1 year after Telethon003 infusion (as compared with pre-GT values) in PBMC and/or T-cell lines. The degree of correction was evaluated with respect to healthy controls.