Amendment 1: At the request of HCB and transmitted by the ANSM during the clinical and pharmaceutical evaluation of the AEC file, it was asked to specify the procedures for the transfer of the material (catheters) under a PSMII for purging.

Amendment 2: In order to follow up on the 4 patients included in the clinical trial, the period of observation and follow-up of the safety of the test treatment is prolonged until 30 months post-surgery with the continuation of the treatment. immunosuppressive therapy (tacrolimus Modigraf®). This will track the progress of patients' health status and collect additional safety data and samples to meet protocol objectives.

Amendment 3: 1) Change of the Promoter of the study. The Institut Pasteur transfers the legal and operational responsibility of this trial to a Dutch biotech company, uniQure biopharma B.V. (Tafelbergweg 51, 1105 BD Amsterdam, the Netherlands). 2) Extension of follow-up of 4 patients included in the 36-month clinical trial. Version 5 of protocol consisted in extending the follow-up of the 4 patients to 18 months post-surgery. With this second phase of extension, the total follow-up of the children will be 5 years, in accordance with the recommendations of the European Medicines Agency on the follow-up of patients administered with a gene therapy (EMEA / CHMP / GTWP / 60436 / 2007). It should be noted that during this second phase of extension, the dose of tacrolimus will continue to be reduced and potentially stopped from month 48 post-surgery, depending on the results of available immunological data. 3) Addition of serologies to Cytomegalovirus (CMV) and Varicella-Zoster Virus (VZV) at visits V23-M12 and V41-M30 when previous serologies are negative (note that these serologies are performed by the center at the same time as the Epstein-Barr virus serology (EBV), the results will be retrospectively collected for the V23-M12 visit that has already been performed for the 4 patients included). 4) Addition of a blood sample (volume = 3 ml) at visit V41-M30 for the analysis of total and neutralizing antibodies against transgene 5) Clarification that any adverse event spontaneously reported by the patient / parents, observed by the investigator as well as any laboratory or radiological abnormalities that occurred during the extension phase should be documented in the CRF and added a section describing the monitoring and reporting of adverse events qualified for special notification (in agreement with EMEA / CHMP / GTWP / 60436/2007)

Amendment 4: The purpose of the amendment is to incorporate the tacrolimus tapering and discontinuation plan into the current protocol. This includes addition of a new Appendix which outlines the process, as well as adaptation of the protocol itself to include a new M51 (V48) sample and associated updates. In addition, administrative updates related to personnel and address changes were made, as well as correction of some typographical errors identified in the previous version.