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

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Neoplasia
• Intervention / Treatment: Biological: Gardasill 9™ vaccine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mathew Furtado; Phone Number: +44 (0) 20 3311 7046; Email: m.furtado@imperial.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria

Patients who meet all of the following inclusion criteria will be considered eligible for this study:

1. 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
2. Written informed consent obtained from the subject prior to enrolment
3. Free of other relevant health problems as established by medical history and clinical examination, e.g. immunosuppression
4. 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:

1. Use of other investigational/non-registered product within 30 days preceding the 1st vaccine dose
2. Continuous administration of immunosuppressants
3. Previous vaccination against HPV
4. 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
5. Any confirmed or suspected immunosuppressive condition, including HIV infection
6. History of allergic disease or any neurologic disorders likely to interact with study vaccination
7. Acute febrile disease at enrolment (will be postponed)
8. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control; No intervention
EXPERIMENTAL: Vaccinated Arm; Add vaccine	Biological: Gardasill 9™ vaccine; 3 doses of Gardasill 9™ vaccine 0.5 ml administered 3 times at 0, 2 and 6 month

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

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Maria Kyrgiou, Imperial College London

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2019
• Primary Completion (ANTICIPATED): July 31, 2023
• Study Completion (ANTICIPATED): July 31, 2023

Study Registration Dates

• First Submitted: June 4, 2019
• First Submitted That Met QC Criteria: June 5, 2019
• First Posted (ACTUAL): June 7, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 27, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: vaccination; neoplasia; cervix cancer
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: C/39/2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No