Clinical Trial: A Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls
Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional
Official Title: A Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls
Brief Summary: Cervical cancer is the most common cancer in women aged 15-44 years in East Africa, and mortality rates are very high. HPV vaccines are most effective if given to girls who have not yet acquired HPV infection. In Tanzania, HPV vaccine has been shown to be safe, acceptable and can be delivered with high coverage (around 80%). However, the cost of delivering HPV vaccine is considerably higher than costs for traditional infant/child vaccinations. This is primarily because of costs to establish outreach programmes and associated personnel costs including nurses who must spend significant time away from their posts to deliver vaccine, especially if multiple doses are needed. There is global interest in simplifying HPV vaccine delivery by reducing the number of doses. If a single dose could be given, this could halve the costs of delivery, making it more accessible to the populations that need it most. Recently, the WHO recommended that 2 doses of HPV vaccine could be given to young girls, based on studies in high and upper middle income countries. However in Africa high rates of infections like malaria and worms can affect immune responses to vaccines. It is essential to know that reducing the number of doses does not reduce the protective immune response of these vaccines. The investigators are conducting a trial in Tanzanian girls aged 9-14 years to establish whether a single dose of HPV vaccine produces immune responses that are likely to be effective in preventing cervical cancer. Two different HPV vaccines, the bivalent (2-v) vaccine that protects against HPV 16/18 (the cause of 70% of cancers) and a new 9-valent (9-v) vaccine that protects against 9 HPV types, will be compared. The trial will randomise 900 girls to 6 groups and follow them for 36 months. Girls will receive the 2-v or the 9-v HPV vaccine, as 1, 2 or 3 doses. Girls receiving 1 or 2 doses will be compared with those receiving 3 doses of the same vaccine, to ensure that the reduced dose regimen produce
Detailed Summary:
Human papillomavirus (HPV) infection is the primary cause of cervical cancer, a major public health problem in Africa. Currently there are three vaccines (Cervarix, Gardasil® and Gardasil-9®) that offer excellent protection against HPV infection with vaccine-related HPV genotypes. The objective of this trial is to demonstrate non-inferiority of immune responses with 1 dose of HPV vaccine compared with the recommended 2 or 3 doses of the same vaccine by evaluating HPV 16/18-specific seropositivity, antibody avidity and memory B cell responses at M36. Specifically, the investigators will determine whether a single dose of the 2-valent HPV vaccine (Cervarix, that protects against HPV 16/18 genotypes) or of a new 9-valent HPV vaccine (Gardasil-9,that protects against HPV 6/11/16/18/31/33/45/52/58) produces immune responses that are non-inferior to those observed with 3 doses of vaccine when given to HIV-negative 9-14 years old girls in a malaria-endemic region of Tanzania.
The trial will also determine whether the World Health Organization's (WHO) recently recommended 2 dose strategy for girls aged under 15 years produces similar immune responses in Sub-Saharan Africa (SSA) compared to the previously recommended 3 dose schedule. In addition, the cost-effectiveness of alternative dosing schedules and of the two vaccines will be explored.
The trial will enrol 900 girls who are resident in Mwanza into an un-blinded, individually-randomised trial with 6 arms. Arm A will comprise participants randomised to receive 3 doses of the 2-valent vaccine, Arm B those randomised to receive 2 doses of the 2-valent vaccine and Arm C those randomised to receive 1 dose of the 2-valent vaccine. Arms D, E and F will be those participants randomised to receive 3, 2 or 1 dose of the 9-valent vaccine, respectively.
Original Primary Outcome: Same as current
Current Secondary Outcome:
- non-inferiority of HPV 16/18 seropositivity after 1 dose compared with 3 doses of the same vaccine [ Time Frame: Month 12 and Month 24 ]Proportion with HPV 16/18-specific seropositivity
- non-inferiority of HPV 16/18 seropositivity at all time points when comparing 2 doses with 3 doses of the same vaccine. [ Time Frame: Month 12, Month 24 and Month 36 ]HPV 16/18-specific seropositivity
- non-inferiority of HPV 16/18 antibody titre at all time points when comparing 2 doses with 3 doses of the same vaccine. [ Time Frame: Month 12, Month 24 and Month 36 ]HPV 16/18-specific antibody geometric mean titre (GMT)
- equivalence of HPV 16/18 seropositivity when comparing the same dose regimen between the two vaccines [ Time Frame: Month 12, Month 24 and Month 36 ]HPV 16/18-specific seropositivity
- equivalence of HPV 16/18 antibody GMT when comparing the same dose regimen between the two vaccines [ Time Frame: Month 12, Month 24 and Month 36 ]HPV 16/18-specific geometric mean antibody titre
- non-inferiority of HPV 16/18 antibody avidity when comparing 2 doses with 3 doses of the same vaccine type [ Time Frame: Month 36 ]HPV 16/18-specific antibody avidity
- non-inferiority of HPV 16/18 memory B cell responses when comparing 2 doses with 3 doses of the same vaccine type [ Time Frame: Month 36 ]HPV 16/18-specific memory B cell responses
- stability of antibody responses when comparing within the same arm. [ Time Frame: Month 24 and Month 36 ]HPV 16/18-specific antibody titre
- non-inferiority of immune responses when comparing the 1 dose regimen of either vaccine in our 9‒14 year old population with historical data from women aged 18‒25 years who received 3 doses [ Time Frame: M36 ]HPV 16/18-specific seropositivity
- non-inferiority of antibody seropositivity when comparing the 2 dose regimen of either vaccine in our 9‒14 year old population with historical data from women aged 18‒25 years who received 3 doses [ Time Frame: Month 36 ]HPV 16/18-specific seropositivity
- non-inferiority of antibody GMT when comparing the 2 dose regimen of either vaccine in our 9‒14 year old population with historical data from women aged 18‒25 years who received 3 doses [ Time Frame: Month 36 ]HPV 16/18-specific geometric mean antibody titre
- evaluate HPV 6/11/31/33/45/52/58 antibody response with the 1 and 2 dose regimens of the 9-valent vaccine compared with the 3-dose regimen [ Time Frame: Month 12, Month 24 and Month 36 ]HPV 6/11/31/33/45/52/58-specific antibody seropositivity
- unit cost of 1 dose regimens compared with 2 and 3 dose regimens [ Time Frame: up to Month 6 ]incremental financial and economic costs of vaccination, using WHO costing tool
- cost-effectiveness of 1 dose regimens compared with 2 and 3 dose regimens, and of the 9-valent vaccine compared with the 2-valent vaccine [ Time Frame: up to Month 36 ]estimates of costs and effects of vaccination will be integrated into an existing HPV cost-effectiveness model (WHO CHOICE)
- number of participants with treatment related solicited adverse events [ Time Frame: within 30 days after each dose ]solicited adverse events considered to have a reasonable possibility of having been contributed to by the vaccine
- number of participants with treatment related unsolicited adverse events [ Time Frame: up to Month 36 ]unsolicited adverse events considered to have a reasonable possibility of having been contributed to by the vaccine
Original Secondary Outcome: Same as current
Information By: London School of Hygiene and Tropical Medicine
Dates:
Date Received: June 29, 2016
Date Started: August 2016
Date Completion: August 2020
Last Updated: August 1, 2016
Last Verified: August 2016
