-New primary and secondary packaging will be used: the new primary packaging is a sachet (also named stickpack) instead of a pillbox and the new secondary packaging is a cardboard box of 60 units instead of 30. - Operation of packaging of the sachets and pharmaceutical certification done by Ivers-Lee - Change of IMP denomination” according to the CHMP statement on the 4th Apr 2014: “mini-tablets” is replaced by “prolonged-release granules” and all documents are updated with this new denomination. - Homogenisation of the wording for the strength of the doses (use “8 mEq” and “24 mEq”, rather than the dose in mg of active principles or in mg of granules) - Change of the IMP labelling: the mention of trial reference code is not any more indicated in the label and the mentions on primary packaging do not include anymore the treatment number. - Modification of the number of subjects included: “Up to 32 subjects may be enrolled in order to have 24 subjects fully evaluable” - Modification of study duration: extension from 33 to 40 months with 16 months for inclusion part. - Modification of the compliance evaluation: “to allow the investigator evaluating the patient compliance according to several factors: number of unused monodoses, questioning of the patient and/or his parents, observation of the subject’s laboratory results, at each study visit”. - Centralisation of analysis for the 1α,25-dihydroxy-vitamin D, parathyroid hormone and bone alkaline phosphatases with delegation of this activity to a central lab. - Modification of the bone marker to be analysed: “TRAP-5b” is replaced by “a new bone marker “. - Analysis of calcitonine removed - Clarification of the ECG and vital signs exams schedule - Precision done on the definition of an SAE: “any inpatient hospitalisation planned before the study enrolment of the patient or required as part of the usual medical management of the patient’s disease will not be considered as a SAE”

- Modification in the IMP process: the primary packaging will be done packaged by Ivers-lee, the secondary packaging will be done by Ivers-lee or Amatsi, and released by IL-CSM, and they will be released and supplied to the centres by Amatsi, in accordance with the GMP.

- The study duration is extended up to marketing authorisation and provision of the ADV7103 product in France. - Addition of study visits after the initial end of study according to medical practice and on a regular basis at least every 12 months - Addition of exploratory objective: o To explore the ADV7103 treatment acceptability at long term. - Addition of exploratory endpoints: o Treatment acceptability that will be evaluated with Visual Analogue Scales (VAS), to be filled in by the patient or the caregiver (depending of the age), to be scored at M24 o Quality of life of the parents that will be evaluated with a VAS, to be filled in by one of the parents at M24 - Addition of new data to be collected “Disease history”: collection of biological parameters and demographic data in the 4 years prior to B21CS

A patient qualitative interview was conducted to explore the impact of dRTA and its treatments on the daily life of the patients and/or their parents. This evaluation will be done at least after 48 months of study participation. Collection of the dRTA genetic mutation.