Using first-void urine to observe how HPV16 antibodies interact with the virus before and after HPV vaccination

Developing a First-void Urine-based Infection Model to Study HPV-specific Antibody-virion Interaction Before and After Vaccination With the Gardasil-9 HPV Vaccine - a Non-randomized Open-label Study.

This trial will test whether giving two doses of Gardasil 9 to HPV16-positive women aged 18–45 reduces infectious virus in first-void urine and increases HPV-specific antibodies detectable in that urine.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: Universiteit Antwerpen (other)
• Locations: 3 sites (Antwerp, Wilrijk and 2 other locations)
• Trial ID: NCT07407569 on ClinicalTrials.gov

What this trial studies

This open-label, non-randomized, longitudinal Phase 2 trial will enroll about 50 women aged 18–45 who are HPV16 DNA positive but have no visible anogenital lesions and have not previously received an HPV vaccine. Participants will receive two doses of the licensed Gardasil 9 vaccine in an off-label context and will provide serial first-void urine samples over time. The primary goal is to see if vaccination reduces the ability of shed HPV16 particles to infect, using urine-based infectivity measurements, while secondary objectives track HPV16-specific antibody levels in those urine samples. The protocol leverages self-sampling (first-void urine) to minimize invasiveness and to explore a non-blood biomarker approach for mucosal immune responses.

Who should consider this trial

Good fit: Women aged 18–45 who test positive for HPV16 DNA, have no apparent anogenital lesions, have not previously received an HPV vaccine, and can provide informed consent are ideal candidates.

Not a fit: People who are pregnant, already vaccinated against HPV, have current anogenital lesions requiring treatment, or fall outside the age range are not eligible and are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could show that vaccination lowers infectious HPV16 in the genital tract and offer a simple, non-invasive urine test to monitor local antibody responses.

How similar studies have performed: Previous work has detected HPV antibodies in first-void urine and shown prophylactic HPV vaccines prevent new infections, but using urine-based infectivity measures to track vaccine effects in already-infected women is novel and largely untested.

Eligibility criteria

Candidates are eligible for inclusion in the study if they:

* Are females between 18 and 45 years old (including both limits) at the time of signing the informed consent form.
* Have tested positive for HPV16 DNA (single or co-infection) but have no presence of apparent anogenital lesions and are thus not referred for treatment or intervention at the time of inclusion or within the last twelve months before inclusion.
* Did not receive prior vaccination with a prophylactic HPV vaccine.
* Are able to understand the information brochure and what the study is about.
* Are willing to give informed consent to the study team to access their medical records, including details on their HPV vaccination schedule and cervical cancer screening results (smears, HPV tests, colposcopy, biopsy).

Candidates must be excluded from the study if they:

* Are previously (completely or partially) vaccinated against HPV or have planned administration of another HPV vaccine during the study.
* Are pregnant at the time of signing informed consent or are planning to become pregnant within the full duration of the study. Participants must use an effective method of contraception throughout the entire study. Acceptable methods include combined hormonal contraception (oral, vaginal ring, transdermal patch), progestogen-only contraception (oral, injectable, implantable), intrauterine device (IUD)/intrauterine system (IUS), condom, vasectomized male partner, or (periodic) abstinence. Lactating women may be included.
* Have had full hysterectomy.
* Have had any anogenital lesion treated in the last twelve months before participating in the study.
* Have invasive cancer (except basocellular carcinoma) or other immunocompromising conditions as described as high-risk in the latest scientific guidelines from Sciensano.
* Use immunosuppressive therapy for inflammatory bowel disease, rheumatological disorders, neuromyelitis optica, sarcoidosis, adenocarcinoma in situ, or use of local anogenital corticosteroids.
* Have used any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planning to use during the study period.
* Have received immunoglobulin or blood-derived products in the three months prior to the first study vaccination (Month 0), or are expected to require immunoglobulin or blood-derived products from Month 1 until Month 7 of the study.
* Receive any vaccine not foreseen in the study protocol administered in the period beginning 30 days preceding each dose of the study vaccine and ending one month (minimum 30 days) after each dose of the study vaccine.
* Have known allergy or history of any reaction or hypersensitivity likely to be exacerbated by any component of the Gardasil 9 vaccine or known history of severe allergic reaction to other vaccines (e.g. anaphylaxis).
* Are concurrently enrolled in another clinical study of investigational agents.
* Have acute disease or contraindications for vaccination at the time of enrolment. Acute disease is defined as the presence of moderate or severe illness with or without fever. Enrolment will be deferred until the condition is resolved. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e. oral/axillary temperature \>37.5 °C.
* Have a history or current evidence of any condition or abnormality that might confound the results of the study or is not in the best interest of the individual to participate, in the opinion of the investigator.
* Are, as determined by the investigator, unlikely to adhere to the study procedures, keep appointments, or are planning to relocate from the area prior to completion of the study.

Where this trial is running

Antwerp, Wilrijk and 2 other locations

• Antwerp University Hospital — Antwerp, Wilrijk, Belgium (RECRUITING)
• University Hospital Ghent — Ghent, Belgium (RECRUITING)
• University Hospital Leuven — Leuven, Belgium (RECRUITING)

Study contacts

• Study coordinator: Margo Bell

Conditions: Human Papilloma Virus Infection Type 16, HPV-specific antibodies, Gardasil 9, Vaccination, Self-sampling, First-void urine