Study amendments
choroideremia, vision loss
ADVERSE EVENTS, SECONDARY, ADVERSE EVENT, CHOROIDEREMIA, ADVERSE REACTION
There were four protocol amendments. Amendment 1 occurred on 10 November 2015, and it removed treatment of timrepigene emparvovec of the fellow eye that was originally planned for 4–6 participants. Also, it removed the requirement for conducting the International Reading Speed Test in countries where validated translations were not available. Amendment 2 occurred on 26 February 2016 and led to the following changes:Changed volume of timrepigene emparvovec subretinal injection from 0.05 ml to 0.1 ml (containing 1 × 10Changed visual acuity inclusion criterion for the study eye from a BCVA of 34–78 letters to a BCVA of 34–73 lettersRemoved randomization method for selection of the ‘study eye’ and replaced with a requirement for the investigator to use clinical judgment (in collaboration with the participant) to select the study eye, which was generally the worse eyeClarification of management of screening identification and inclusion of screen failure dataRemoved reference to an Interactive Voice/Web Response System for purposes of treatment randomizationIncluded prednisone (in addition to prednisolone) as the corticosteroid of choice in the 21-d perioperative periodAdded requirement that participants must have had a genetically confirmed diagnosis of choroideremia before the screening visit (visit 1)Visit windows for visits 7, 8 and 9 decreased from ±21 d to ±14 dAmendment 3 occurred on 1 August 2017 and included an updated title to reflect changes in the study design; a change in choice in study control and randomization to a parallel, untreated control three-arm study design (high dose, low dose and untreated control); an increase in sample size from 100 to 140 participants; a change to the primary endpoint from improvement of 10 ETDRS BCVA letters to 15-letter improvement; and a change to the key secondary endpoint to use the NIGHT study as a historical control. Amendment 4 occurred on 15 March 2019 and included an increase of sample size to 160 participants; a change of the key secondary endpoint from a historical comparison to the NIGHT study to prospective within-study assessments; the addition of a risk–benefit assessment to clarify vision loss as a known possible adverse event (AE) (and definition of serious adverse events (SAEs) associated with vision loss), therefore precluding it from Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting; and the definition of day 0 for untreated participants to assure that the duration of follow-up was equal for both treated and untreated participants.