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

NCT ID: NCT03979014

Last Updated: 2026-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1099 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-01
• Study Completion Date: 2025-09-05

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.

Conditions

Neoplasia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Vaccinated Arm

Add Vaccine

Group Type: EXPERIMENTAL

Gardasill 9™ vaccine

Intervention Type: BIOLOGICAL

3 doses of Gardasill 9™ vaccine 0.5 ml administered 3 times at 0, 2 and 6 month

Control

No intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Gardasill 9™ vaccine

3 doses of Gardasill 9™ vaccine 0.5 ml administered 3 times at 0, 2 and 6 month

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

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

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Imperial College London

OTHER

Sponsor Role: lead

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria Kyrgiou, MBBS, FRCP

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Helsinki University Hospital

Helsinki, , Finland

Tampere University Hospital

Tampere, , Finland

Regionhälsan Masthugget Clinic of Obstetrics and Gynecology

Gothenburg, , Sweden

Sahlgrenska University Hospital

Gothenburg, , Sweden

Frölunda Specialist Hospital Gynecology Clinic

Västra Frölunda, , Sweden

St James's University Hospital, Leeds

Leeds, England, United Kingdom

Guy's and St Thomas' NHS Foundation Trust

London, England, United Kingdom

West Middlesex University Hospital

London, England, United Kingdom

St. Mary's Hospital - Manchester University NHS Foundation Trust

Manchester, England, United Kingdom

Whittington Health NHS Trust

Middlesex, England, United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, England, United Kingdom

Royal Preston Hospital - Lancashire Teaching Hospitals NHS Trust

Fulwood, Preston, United Kingdom

St Mary's Hospital - Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

Finland; Sweden; United Kingdom

References

Joura E, Kjaer SK, Bautista O, Luxembourg A, Saah A, Giuliano A. Effect of Prior 9-Valent Human Papillomavirus Vaccination on Subsequent Lower Genital Tract Dysplasia After Cervical Excisional Surgery. Obstet Gynecol. 2026 Jan 1;147(1):73-82. doi: 10.1097/AOG.0000000000006113. Epub 2025 Oct 30.

Reference Type: DERIVED

PMID: 41166720 (View on PubMed)

Other Identifiers

C/39/2018

Identifier Type: -

Identifier Source: org_study_id