Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03675256 |
| Other study ID # |
2022P001178 |
| Secondary ID |
OPP1188693 |
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
December 19, 2018 |
| Est. completion date |
February 15, 2024 |
Study information
| Verified date |
December 2023 |
| Source |
Massachusetts General Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The KEN SHE Study aims to identify effective cervical cancer prevention strategies. Cervical
cancer is caused by an infection with Human Papillomavirus, also called HPV. In Kenya, about
2,500 women die from this condition each year. The study is conducted by Kenya Medical
Research Institute (KEMRI) sites, based in Kisumu, Thika and Nairobi and the University of
Washington, Seattle, USA.
The purpose of this study is to learn whether a single dose of the HPV vaccine prevents HPV
infection among adolescents and young women. Using a single dose will lower the cost of
providing HPV vaccination (compared to two doses) and will make it possible for more women to
receive the vaccination and be protected from cervical cancer.
The study will involve approximately 21 clinic visits over a period of 55 months. All visits
will involve blood draws and many will involve pelvic swabs. Participants will receive an
FDA-approved HPV vaccine and a meningococcal vaccine.
Description:
Cervical cancer is the leading cause of new cancer cases among women in Africa. Preliminary
evidence suggested a single-dose of the HPV vaccine would be over 95% effective in preventing
vaccine type-specific HIV infection, supporting HPV vaccination as a scaleable intervention
for cervical cancer prevention. The overall aim of the study is to provide timely results of
both single-dose HPV vaccine efficacy and estimates of the cost, cost-effectiveness, and
budget impact for dissemination and translation to policy. Several HPV vaccines are
available. The KEN SHE Study will determine the efficacy of two HPV vaccines: bivalent and
nonavalent vaccines.
At the start of the study, young women were randomly sorted into three arms. In arm 1, the
women received the bivalent HPV vaccine. In arm 2, the women received the nonavalent HPV
vaccine. And in arm 3, the women received a meningococcal vaccine. The three-arm study
structure makes it possible to compare the women who received an HPV vaccine to those who did
not receive an HPV vaccine during the study. A formal primary analysis was planned to be
conducted after 18 months of follow-up to provide early evidence on single-dose HPV vaccine
efficacy.
The principal results of the primary analysis conducted 18 months after enrollment were to
demonstrate whether the single-dose HPV vaccine strategy prevents incident persistent HPV
vaccine type specific infection among young women, by comparing the rate of new HPV
infections among women who receive the vaccine immediately to those receiving delayed
vaccination. Single dose HPV vaccination was highly effective at the month 18 primary
analysis timepoint. Thus, as recommended by the Data Saftey Monitoring Board, participants
should receive a blinded crossover vaccination. Participants who received the HPV vaccine at
enrollment will receive the meningococcal vaccine and participants who received the
meningococcal vaccine at enrollment, will receive the HPV vaccine (i.e. crossover
vaccination). Questions remain regarding the durability of single-dose HPV vaccine efficacy
which may limit the uptake of single-dose HPV vaccination. To ensure that vaccine efficacy is
durable, crossover vaccination and follow-up will be conducted using a blinded crossover
study design. This design will allow comparison of the early and late vaccine efficacy to
ensure that single-dose HPV vaccine clinical efficacy does not wane over time. Thus, the
study will contribute data on both single-dose HPV vaccine efficacy and durability of the
effect. A final analysis will be conducted with the conclusion of up to 55 months of
follow-up; if waning protection is detected, participants will receive the World Health
Organization recommended course of HPV vaccination.
With the introduction of the crossover vaccination, the primary study endpoint is now
persistent vaccine type specific HPV infection at months 18 and 18 months after blinded
crossover vaccination. The quantitative antibody response will be documented at months 1 and
24 to support immunobridging analyses to girls and adolescents for the single-dose bivalent
and nonavalent vaccines. Using the data on persistent infections and health economic models,
we will assess the impact on cervical cancer incidence. Specifically, investigators will
compare the incidence of high-risk vaccine HPV types overall and the distribution of HPV
types by study arm. Investigators will assess the immunologic response to single-dose HPV
vaccination, specifically regarding long lasting B cell responses to support the durability
of the single-dose vaccination approach. Data on the magnitude of the antibody response at
months 1 and 24 will support immunobridging analyses to young girls and adolescents. The 24
month antibody result will be used to assess durability of the response and will be directly
comparable to other studies of the single-dose HPV vaccine which are uniformly using the
month 24 antibody result as the primary outcome. Further, among the women who received
immediate HPV vaccine, investigators will estimated the durability of the bivalent and
nonavalent HPV vaccines by measuring the antibody response and cumulative incidence of
persistent cervical HPV over the duration of follow-up. Costing analyses will assess the
resources required for scale-up of single-dose HPV vaccination.
Enrollment took 12 months and there are 55 months of follow-up for each participant. The
endpoint-driven trial design among women at risk of HPV acquisition will provide primary
results after 18 months of follow-up, and, with the extended follow-up, evidence on
durability over three years. The study duration is 78 months.
