Nonavalent Prophylactic HPV Vaccine (GARDASIL9) After Local Conservative The NOVEL Trial

Study Overview
=================
Brief Summary
-----------------
The researchers involved in this new study are interested in whether giving a HPV vaccine to women at the same time as conisation can lead to a greater rate of HPV clearance compared to conisation on its own, and a result reduce the occurrence of further infection and high grade CIN. The study will do this by using a specific HPV vaccine called Gardasil 9™ which protects against 9 types of HPV infection (types 6, 11, 16, 18, 31, 33, 45, 52 and 58).

Detailed Description
-----------------
The human papilloma virus (HPV) can cause high grade intra-epithelial neoplasia (CIN) in women, a condition where there are abnormal cells on the surface of the cervix (the opening to the vagina from the womb). High grade CIN can develop into cervical cancer, and standard treatment is a surgical procedure called conisation, where a scalpel or laser is used to remove a cone-shaped piece of the cervix containing the abnormal cells. HPV vaccines are routinely used in adolescent girls as part screening programmes to prevent cervical cancer (12-18 years of age in the UK). The NOVEL study will compare the vaccine approach with standard treatment in a randomised controlled trial, where eligible women will be randomly allocated to one of the following: Arm 1: Local Cervical treatment and vaccination with Gardasil 9, followed by additional vaccinations 2 and 6 months after conisation Arm 2: Local Cervical Treatment and Observation This study is for women aged 18-55 years of age with biopsy confirmed high-grade CIN. 1000 women will be recruited at colposcopy clinics in the UK, Finland and Sweden. Women will be followed up for a maximum of two and a half years.

Official Title
-----------------
Nonavalent Prophylactic HPV Vaccine (GARDASIL9) After Local Conservative Treatment for Cervical Intra-epithelial Neoplasia: a Randomised Controlled Trial - The NOVEL Trial

Conditions
-----------------
Neoplasia

Intervention / Treatment
-----------------
* Biological: Gardasill 9™ vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Patients who meet all of the following inclusion criteria will be considered eligible for this study: Female (18-55y) attending for local treatment for presumed CIN2 (cytological and colposcopy impression) OR presumed CIN3 (cytological and colposcopy impression) OR presumed cGIN/AIS (cytological and colposcopy impression) OR biopsy-confirmed CIN2 OR biopsy-confirmed CIN3 OR biopsy-confirmed CGIN/AIS Written informed consent obtained from the subject prior to enrolment Free of other relevant health problems as established by medical history and clinical examination, e.g. immunosuppression Patients who the investigator believes can and will comply with the protocol requirements (e.g. attendance at clinic appointments and return for follow-up visits) Exclusion criteria Patients who meet any of the following exclusion criteria will not be eligible for this study: Use of other investigational/non-registered product within 30 days preceding the 1st vaccine dose Continuous administration of immunosuppressants Previous vaccination against HPV Cancer or autoimmune disease under treatment. Patients who have a history of cancer or autoimmune disease but are not currently being treated for the condition will be included Any confirmed or suspected immunosuppressive condition, including HIV infection History of allergic disease or any neurologic disorders likely to interact with study vaccination Acute febrile disease at enrolment (will be postponed) Pregnant women or women intending to get pregnant during the next 6 months (if pregnant during follow-up, remaining doses will be delayed until after delivery)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccinated Arm<br>Add vaccine | Biological: Gardasill 9™ vaccine<br>* 3 doses of Gardasill 9™ vaccine 0.5 ml administered 3 times at 0, 2 and 6 month<br>|
| No Intervention: Control<br>No intervention | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of HPV infection in women with high grade cervical intra-epithelial neoplasia after vaccine Gardasil 9™ assess by laboratory test | High grade CIN is a condition where there are abnormal cells on at least two-thirds of the surface of the cervix (the opening to the vagina from the womb). Gardasil 9™ will be given at the same time as localised cervical treatment, a procedure which uses a scalpel or laser to remove a cone-shaped piece of the cervix containing the area with abnormal cells. | 2 years after first dose of vaccine | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neoplasia, cervix cancer, vaccination