A total of 4,065 men were enrolled. Ten subjects who were randomized in error and did not receive vaccination were excluded from the safety analyses. In addition, six subjects (five subjects who were randomized to receive qHPV vaccine and 1 subject who was randomized to receive placebo) received protocol non-compliant vaccination regimens (mixed regimens of vaccine and placebo) and were also excluded from the current report. A total of 4,049 males who received at least one dose of qHPV vaccine or placebo were included in this report. The safety profile of the qHPV vaccine was generally comparable in MSM and HM subjects; safety data are therefore presented for the overall study population.
Compliance in returning diary cards was high for vaccine and placebo groups, n = 1,945 (96.3%) and n = 1,950 (96.1%), respectively. On days 1–15 following vaccination the proportion of subjects who reported at least one clinical AE or at least one injection-site AE was slightly higher in the qHPV vaccine group than in the placebo group (69.2% vs. 63.8% and 60.1% vs. 53.7%, respectively; p < 0.001) (). In addition, the proportion of subjects who reported at least one systemic AE was generally comparable between the vaccine and placebo groups (31.7% vs. 31.4%, respectively) (). As seen in , AEs reported at any time during the study were comparable to those observed on days 1–15 following vaccination. Few subjects who received qHPV vaccine or placebo discontinued the study due to an AE (0.3% vs. 0.7%, respectively) (). Five males in the vaccine group discontinued the trial or did not receive all three vaccinations; only two of the five men's reasons for discontinuation were deemed related to vaccination (malaise and headache). The other reasons included vertebral fracture, gun shot wound, traumatic brain injury and road traffic accident. Fourteen males in the placebo group discontinued the trial or did not receive all three vaccinations. There were no vaccine-related SAEs.
Summary of adverse experiences among all subjects during days 1–15 following vaccination
Summary of adverse experiences among all subjects during the entire study period
AE data following each injection of qHPV vaccine or placebo indicate that the occurrence of AEs did not increase with each successive injection (). After the first dose of qHPV vaccine 53.6% of subjects reported at least one AE. After doses 2 and 3 this number fell to 42.4% and 39.3%, respectively.
Clinical adverse experience summary for days 1–15 following each vaccination
A total of 13 subjects died during the study ( and
). Causes of death for the 10 participants in the placebo group included accidental illicit drug overdose,2
motor vehicle accident, gun shot wound,3
poisoning and ischemic heart disease. Causes of death for the three participants in the qHPV vaccine group included motor vehicle accident2
and gun shot wound. None of the deaths were vaccine-related.
A summary of the number and percentage of subjects with injection-site AEs and fever within five days following any vaccination visit can be seen in . Vaccine recipients (59.9%) were more likely than placebo recipients (53.6%) to report injection-site AEs, the most common of these being pain at the site (risk difference, 6.4%; 95% CI 3.3 to 9.5). Injection-site erythema, swelling and pruritus were less common and similar proportions of vaccine and placebo recipients reported them. Among trial participants who were seropositive for one or more of the four HPV types at day 1, the profile of adverse events was similar to that of the entire study cohort (data not shown).
Summary of specific injection-site adverse experiences (days 1–5 following any vaccination visit)
In , we provide a summary of the number and percentage of subjects who reported systemic clinical AEs by system organ class (incidence ≥1%) within 15 days following any vaccination visit. The percentage of subjects who reported one or more systemic AEs was comparable between the qHPV vaccine group (31.7%) and the placebo group (31.4%). The most common individual clinical AEs reported was headache (9.2% in the vaccine group and 10.6% in the placebo group), followed by pyrexia oral temperature ≥37.8°C (100°F). The number of subjects who reported an oral temperature ≥37.8°C (100°F) was similar in the qHPV vaccine and placebo groups (6.2% vs. 6.4%, respectively).
Summary of systemic clinical adverse experiences (≥1%) among participants with detailed safety data (days 1–15 following vaccination)
The majority of both injection-site and systemic AEs were mild or moderate in intensity (as judged by maximum intensity rating) from days 1–15 following injection of qHPV vaccine or placebo ( and B). Approximately 80% and 50% of the reported injection-site and systemic AEs among qHPV recipients were mild in intensity, respectively.
Summary of injection-site experiences by maximum intensity rating (days 1–15 following vaccination)
The most common new medical conditions reported during the vaccination period (day 1 to month 7) were nasopharyngitis and pharyngitis. The proportion of subjects reporting new medical conditions during the vaccination period remained generally comparable between the vaccination groups (24.7% vs. 22.8% in the qHPV vaccine and placebo groups respectively) (data not shown). The most commonly reported new medical conditions during the follow-up (post month 7) period were upper respiratory infections and pharyngitis. The proportion of subjects reporting new medical conditions during follow-up remained generally comparable between the vaccination groups (28.2% vs. 30.0% in the vaccine and placebo groups respectively) (data not shown).