Pilot efficacy bridging study of two human papillomavirus vaccines administered intradermally and intramuscularly

INTERVENTION: A total of 40 female subjects aged 18‐26y at the start of the study will be enrolled. After consent, all subjects will have blood taken for serum antibody to HPV16 and HPV18. Those subjects who test negative for both HPV16 and HPV18 will be randomised, using simple randomisation. Subjects will be vaccinated on Day 1, Month 2 (+/‐ 2 weeks) and Month 6 (+/‐ 2 weeks). Five subjects for each vaccine type will receive full dose (0.5ml) intramuscularly, five will receive 20% (0.1ml) of the full dose intramuscularly, five will receive a 20% (0.1ml) of full dose intradermally via an intradermal injection device, and five will receive 20% (0.1ml) of full dose intradermally with a tuberculin syringe and needle for all three vaccine doses. An equal number of subjects will receive Gardasil and Cervarix. As this study involves three clearly identifiable routes of administration for the two vaccines, this will not be a double‐blind study. Prior to starting the main study a 20%‐dose of Cervavix vaccine (0.1‐ml) and a 20%‐dose of Gardasil vaccine (0.1‐ml) will each be given intradermally via syringe and needle to ten adult males with 5 subjects receiving each vaccine to ensure that no unexpectedly severe reactions occur with the Cervavix vaccine which contains a novel adjuvant (ASO4) that has not been administered intradermally before and could be more reactogenic than vaccines such as Gardasil containing traditional alum adjuvants. Subjects in this reactogenicity assessment will complete Diary Cards, undergo two blood tests and photographs of the skin reactions will be taken. CONDITION: Human papilloma virus (HPV) infection PRIMARY OUTCOME: Proportion of subjects receiving a reduced‐dose intradermal schedule, that have a type‐specific antibody response to the human papilloma virus vaccine 30 days after the third (month 6) vaccination, that is non‐inferior to the type‐specific antibody response of those subjects receiving a full‐dose intramuscular schedule of the vaccine. The antibody response will be defined by geometric mean titres and seroconversion rates. INCLUSION CRITERIA: Female subjects will be eligible to participate in the study if they: 1. Are 18‐26 years of age at the start of the study; 2. Participants have an understanding of the study, agree to its requirements, and give written informed consent prior to study entry; 3. Are generally healthy; 4. Agree to keep a record of symptoms for 14 days after each vaccination; 5. Are sexually naive. SECONDARY OUTCOME: Immunogenicity: Compare the levels of type‐specific antibody response developed following administration of the two different vaccines after the first, second and third vaccinations. Immunogenicity: Compare the levels of type‐specific antibody response developed following administration of the two different vaccines given by the two different intradermal methods (jet injector and 30 gauge needle/syringe) after the first, second and third vaccinations. Immunogenicity: Proportion of subjects receiving a reduced‐dose intradermal schedule, that have a type‐specific antibody response to the human papilloma virus vaccine 30 days after the first (day 1) vaccination, that is non‐inferior to the type‐specific antibody response of those subjects receiving a full‐dose intramuscular schedule of the vaccine. The antibody response will be defined by geometric mean titres and seroconversion rates. Immunogenicity: Proportion of subjects receiving a reduced‐dose intradermal schedule, that have a type‐specific antibody response to the human papilloma virus vaccine 30 days after the second (month 2) vaccination, that is non‐inferior to the type‐specific antibody response of those subjects receiving a full‐dose intramuscular schedule of the vaccine. The antibody response will be defined by geometric mean titres and seroconversion rates. Safety: Frequency and severity of occurrence of severe adverse events observed during the entire study period. Safety: Proportion of subjects with administration site reactions after the first, second and third vaccination Safety: Proportion of subjects with systemic reactions after the first, second and third vaccination