Effectiveness Study of Human Papilloma Virus (HPV) Vaccines to Prevent Recurrence of Genital Warts (TheraVACCS)

January 6, 2026 updated by: Professor Greta Dreyer, University of Pretoria

Prophylactic Vaccines as Therapy: Prevention of Recurrence of Extensive Genital Warts

Large genital warts are frequently diagnosed in general gynaecology and oncology clinics in South Africa. Medical and destructive therapy for small warts is generally very effective, however unique problems posed by large or extensive genital warts are not so easily solved and treatment of affected patients remains very challenging. Recurrences are common especially among immune-compromised women. This study will test whether giving the quadrivalent human papilloma virus (HPV) vaccine to women with extensive genital warts prior to surgical treatment will improve outcomes. Investigators hypothesize that pre-treatment with HPV vaccine can play a role in the control of both malignant and benign HPV disease in women with and without HIV infection through stimulation of the antibody response. In addition, HPV types and other associated diseases will be studied in women receiving HPV vaccine and placebo.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patient selection:

Female patients referred or presenting with genital warts at each site will be eligible and evaluated against the inclusion and exclusion criteria.

Women who are clinically or severely immune-compromised will not be included into the study, but both HIV negative and HIV infected women will be included. Seventy-five women with large or recurrent genital warts will be recruited for this study from 2 sites in South Africa.

Recruitment:

Women with genital warts will be evaluated for inclusion into the study. Those who fit the inclusion criteria and are without any of the exclusion criteria will be fully informed and invited to participate. The first target will be to recruit the first seventy-five consecutive eligible patients who have signed written consent; recruitment for the study will be done for at least 24 months.

First clinical visit:

  • Evaluation genital lesions:

On study entry tumour size and position will be documented graphically and photographically and viral typing from the vulva wart and cervix will be done using Roche Linear Array test.

  • Evaluation immune status:

HIV status and CD 4/CD 8 count will be recorded and tested and the serum will be collected for antibody testing. Cervical disease of clinical significance will be excluded or treatment offered if relevant.

  • Randomization:

Patients will be randomized to receive either quadrivalent HPV or Hepatitis B vaccine.

  • Vaccination:

The participants assigned to the test group will be administered quadrivalent HPV vaccine in three doses as recommended by the manufacturer. Participants assigned to the control group will receive Hepatitis B vaccine in three doses as recommended by the manufacturer.

Follow-up clinical visits: week 8, week 16 and week 24:

  • Evaluation genital lesions:

Three follow up visits will be scheduled two months apart at which time the lesion size will be recorded.

  • Evaluation immune status:

After month 6 or the third visit, the serum will again be collected for antibody level testing.

  • Treatment decision:

According to the clinical response as measured at month six and onwards, locally destructive or surgical treatment will be allowed according to the preference of the clinician and as determined by clinical factors.

Follow up after treatment:

  • Follow up will be done at six monthly intervals.
  • Evaluation genital lesions:

At these visits lesion size will be determined and documented. HPV typing on the cervical and vulval lesions will be repeated at least once.

  • Further treatment of warts:

If needed, repeat surgery and/or local destruction will be allowed and documented. These will be around week 48 and week 72, or study exit

Study exit:

  • Participants will exit the study in week 72.
  • In the absence of harm as determined at interim analysis or suggested by participant disease history, researchers will be unblinded for participant status at study exit and alternative vaccines will be offered to each of these women.

Study Type

Interventional

Enrollment (Actual)

52

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • Gauteng
      • Pretoria, Gauteng, South Africa
        • Steve Biko Academic Hospital
    • Western Cape
      • Cape Town, Western Cape, South Africa
        • Tygerberg hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female patient > 16 years
  • Presence of vulvo vaginal genital warts: largest tumour diameter > 3 cm OR Tumour on labia minora and labia majora OR bilateral > 1 cm each side OR Tumour in vagina/cervix as well as on vulva > 1 cm lesion each
  • HIV negative or HIV infected and CD4 ≥ 300 cells/mm3 OR viral load controlled OR anti retro-viral (ARV) compliant > 6 months

Exclusion Criteria:

  • Pregnant of planned pregnancy within 6 months
  • Not able to comprehend study method or not able to attend all study visits
  • Previous HPV vaccination
  • Active known opportunistic infection or malignancy including Pneumocystis pneumonia (PCP),Pulmonary tuberculosis (PTB), oesophageal Candida or Kaposi sarcoma or lymphoma
  • Known allergy to vaccines or content of vaccine
  • Previous radiation for genital warts

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Quadrivalent HPV vaccine
Three doses of 4 HPV vaccine is given at registered intervals.
Biological: Quadrivalent HPV vaccine
Quadrivalent HPV vaccine doses administered intramuscular as 3 separate 0.5 ml doses at month 0, month 2 and month 6.
Other Names:
  • Gardasil
  • 4 HPV vaccine
  • q HPV vaccine
Sham Comparator: Hepatitis B vaccine
Three doses of Hepatitis B vaccine is given at the same intervals as the quadrivalent HPV vaccine.
Biological: Hepatitis B vaccine
Hepatitis B vaccine doses administered intramuscular as 3 separate 0.5 ml doses at month 0, month 2 and month 6.
Other Names:
  • Hep B vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Maximum Size of the Genital Wart Lesion Over the Trial Period (as Measured in mm)
Time Frame: Baseline, week 8, 24, 60
The number of participants in whom the size of the genital wart lesion(s) measured smaller at Week8, Week24 and Week60 as compared to their baseline measurement (all measured in mm).
Baseline, week 8, 24, 60

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Acquire Measurable Levels of HPV Type Specific Antibodies During the First 18 Months of the Trail as Measured Using a Competitive Luminex Immuno-assay (cLIA; Reported in Milli-Merck Units [mMU]/ml)
Time Frame: Week 36+
Week 36+
Number of Participants Who Change From HPV 6 DNA Positive in Warts to Negative at Week 72
Time Frame: Baseline, week 72
The number of participants who change from HPV 6 DNA positive in warts to HPV 6 DNA negative at week 72
Baseline, week 72
Number of Participants Who Change From HPV 11 DNA Positive in Warts to Negative at Week 72
Time Frame: Baseline, week 72
The number of participants who change from HPV 11 DNA positive in warts to negative at week 72
Baseline, week 72
Number of Participants Who Change From HPV 16 DNA Positive at Baseline to Negative at Week 60
Time Frame: Baseline, week 60
The number of participants who change from HPV 16 DNA positive at baseline to negative at week 60
Baseline, week 60
Number of Participants Who Change From HPV 18 DNA Positive at Baseline to Negative at Week 60
Time Frame: Baseline, week 60
The number of participants who change from HPV 18 DNA positive at baseline to negative at week 60
Baseline, week 60

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Change From HIV Negative at Baseline to Positive at Week 48
Time Frame: Baseline, week 48
The number of participants who change from HIV negative at baseline to positive at week 48
Baseline, week 48
Number of Participants Who Require Surgical Treatment of Warts at Any of the Clinical Assessments During the Trial, as Judged by the Attending Clinician.
Time Frame: Week 24, 72
The number of participants who require surgical treatment of warts at any of the clinical assessments during the trial, as judged by the attending clinician.
Week 24, 72
Number of Participants Who Require Surgical Treatment of Cervical Disease at Any of the Clinical Assessments During the Trial, as Judged by the Attending Clinician.
Time Frame: Week 24, 72
The number of participants who require surgical treatment of cervical disease at any of the clinical assessments during the trial, as judged by the attending clinician.
Week 24, 72

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pretoria

Collaborators

University of Stellenbosch

Investigators

  • Principal Investigator: Greta G Dreyer, MMed(O&G)PhD, University of Pretoria

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2018

Primary Completion (Actual)

July 31, 2025

Study Completion (Actual)

July 31, 2025

Study Registration Dates

First Submitted

April 12, 2016

First Submitted That Met QC Criteria

April 22, 2016

First Posted (Estimated)

April 25, 2016

Study Record Updates

Last Update Posted (Actual)

January 23, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Merck-MISP-53183

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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