Randomization and masking
CHUV
Eligible participants were enrolled and randomly assigned to receive PepGNP-Dengue or vehicle-GNP on the day of the first vaccination (day 0). Vehicle-GNP was chosen as a control to better isolate the effect of the DENV peptides from that of the gold nanoparticles. Four computer-generated stratified randomization lists (LD and HD, pioneers and followers) were created by CHUV pharmacists. The protocol followed a risk-minimizing dose-escalation strategy, where enrolment and randomization were carried out sequentially, conditional on favourable interim safety analyses. Since this is a first-in-human trial, only one participant was vaccinated per day for the first three ‘pioneer’ participants in each dosage group (randomization by block of three, 2:1, vera, comparator). After a first safety review of the three LD ‘pioneers’ performed by a Pharmacovigilance clinical research organisation (CRO), ten LD ‘follower’ participants were randomized by block of five (8:2, vera, comparator) and vaccinated. An independent data and safety monitoring committee (DSMC), comprising one vaccinologist, two clinical pharmacologists, and one statistician, performed a planned safety analysis prior to dose escalation, reviewing the safety data of the thirteen LD participants before proceeding to LD group second vaccinations and HD group first vaccinations. Safety data of the three HD ‘pioneers’ were reviewed by the Pharmacovigilance CRO before randomizing (block of 5, 8:2, vera, comparator) and vaccinating the ten HD ‘followers’. In addition, specific safety holding rules were defined to trigger immediate suspension of the trial (where restart would have been subject to DSMC review and Ethics Committee approval). These rules are detailed in Only pharmacists responsible for vaccine product reconstitution (but not involved in collection or production of safety and immunological data) had access to the allocation list. The investigators, sponsor, and participants were masked to group assignment. PepGNP-Dengue and vehicle-GNP syringes were identical in volume and appearance. The clinical and immunological teams remained blinded until the respective databases were frozen.