Phase I

In stage I, a total of 56 volunteers aged 18–50 years were randomised with an allocation ratio of 3:3:1 into three arms to receive 3 µg of the vaccine (24 participants), 5 µg of the vaccine (24 participants) or placebo (8 participants) on days 0 and 14. Randomisation was conducted in two stages. Initially, 14 participants were randomised to receive the 3 µg dosage of the vaccine or placebo (12 vs 2). Participants were monitored for 7 days after injection, followed by a DSMB meeting that approved the vaccine safety and authorised further proceeding. The remaining 42 individuals were randomised to the 3 µg, 5 µg, and placebo arms. The randomisation sequence was generated by a computer in a block size of 7. Two types of randomisation blocks were used, corresponding to the two randomisation steps. The first two blocks allocated six participants to the 3 µg vaccine group and one to the placebo group. The remaining six blocks were randomised with an allocation ratio of 2:4:1, in which participants were assigned to three study groups: 3 µg of vaccine, 5 µg of vaccine or placebo, respectively (figure 2).

Diagram of screening, enrolment, randomisation and follow-up in stage I of phase I. RT-PCR, reverse transcription PCR.

In stage II of phase I, after a review of the safety and immunogenicity data of this age group by the DSMB, 32 volunteers aged 51–75 years were enrolled to randomly receive 5 µg of the vaccine (24 participants) or placebo (eight participants) on days 0 and 14. The 5 µg dose was favoured over 3 µg due to better immunogenicity based on the interim analysis of stage I. The randomisation sequence was computer generated in permuted blocks of size 4 with an allocation ratio of 3:1. All random allocation processes were performed by an interactive web response system (figure 3).

Diagram of screening, enrolment, randomisation and follow-up in stage II of phase I. RT-PCR, reverse transcription PCR.