Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT01824537
Other study ID # CIHR-MOP-125949
Secondary ID IIS #38265MOP-12
Status Active, not recruiting
Phase Phase 4
First received
Last updated
Start date September 2013
Est. completion date December 2022

Study information

Verified date October 2022
Source McGill University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Human papillomavirus (HPV) is a member of the Papillomaviridae family of DNA viruses that is capable of infecting humans. HPV infection can cause cancers of the cervix, vulva, vagina, and anus in women or cancers of the anus and penis in men. Two prophylactic vaccines have been proven to be highly effective in preventing the acquisition of HPV infection and the genital precancerous lesions caused by it. However, we do not know yet if a previously infected individual, once vaccinated, would be less infective to her or his sexual partner. We plan to conduct a study, called Transmission Reduction And Prevention with HPV vaccination (TRAP-HPV) study to answer this question. It will include 500 sexually active couples* (total of 1000 individuals) in university student health clinics in Montreal (age 18-45 years). It will be a randomized placebo-controlled, double-blinded intervention trial. Study participants will be followed up to 12 months. Behavioural and biological data will be collected at the time of study enrolment, then at months 2, 4, 6, 9 and 12 post-enrolment. The results of this trial will be invaluable in informing policies regarding vaccination of women and men.


Description:

Two prophylactic vaccines (Gardasil by Merck, and Cervarix by GlaxoSmithKline) have been proven in randomized controlled trials (RCT) to be highly effective in preventing infection against the target HPV types (HPV-6, 11, 16 and 18, for Gardasil, and HPV-16/18, for Cervarix) and the cervical precancerous lesions caused by them. These vaccines have shifted the paradigm of prevention and are expected to have a major impact in reducing the burden of cervical cancer and of other HPV-associated malignancies, such as vulvar, vaginal, penile, anal, and oropharyngeal cancers, as well as benign HPV-associated conditions (in the case of Gardasil), such as anogenital warts and respiratory papillomatosis. However, little is known about the extent with which vaccination may reduce transmission between sexual partners; i.e. much remains to be understood on the effects of HPV vaccine in preventing transmission of target HPV types to sexual partners of vaccinated individuals and its impact on herd immunity. The investigators propose to conduct a placebo-controlled, double-blinded RCT to measure the impact of vaccination in preventing HPV transmission within young (age 18-45) heterosexual couples at McGill and Concordia Universities in Montreal, Canada. Individual partners in 500 couples* will be randomized to a treatment (Gardasil 9) or a control vaccine (Avaxim, a hepatitis A vaccine). This control vaccine provides a similar health benefit incentive as HPV vaccination while preserving the scientific cogency of a "placebo" comparator. Risk factor data will be collected via computerized questionnaires at enrolment (time 0), 2, 4, 6, 9 and 12 months. At all time points, the investigators will measure HPV DNA infection status by PCR in both partners in exfoliated penile, and oral samples from men and vaginal, oral samples from women. Assessing pre-enrolment humoral immune response to HPV infection with a competitive Luminex immunoassay (CLIA) will be done in an enrolment blood sample from all study participants. The primary outcome will be the reduction of HPV DNA positivity for the target HPV vaccine types (types 6, 11, 16 and 18) in multiple anatomic sites in Avaxim-treated sexual partners of participants who received Gardasil 9. The investigators hypothesize that HPV vaccination is effective in reducing the risk of HPV transmission to their sexual partners. They will use the Kaplan-Meier technique and logrank tests to compare the cumulative probability of HPV infection in sexual partners of vaccinated versus unvaccinated individuals against follow-up time, and Cox proportional hazards regression to estimate the effect of vaccination and other covariates on transmission of HPV to sexual partners. Statistical analyses will follow an intention-to-treat approach but additional regression models will examine the role of several candidate determinants in mediating transmission and the protective effects. Mixed-effects models will also be used to take advantage of the repeated measurements across visits, HPV types, and anatomical sites for the same subject. In addition to the findings on protection to unvaccinated partners, it is expected that this study will provide valuable insights as to whether protection may exist for a vaccine recipient in preventing infection in an anatomical site in which a target type has not yet established infection. These findings will generate key parameter data to inform the extent of herd immunity in cost-effectiveness models of HPV vaccination. Such models are essential to arrive at rational science-driven policies of HPV vaccination in girls and boys in Canada. As of March 13, 2020, study visits were temporarily suspended due to the COVID-19 pandemic. With university approval, study visits were resumed as of May 26, 2020. This interruption in study visits lead to slight alterations in the timing of vaccinations, which will be adjusted for in the final analyses as required. *Due to challenges with participant recruitment, we will complete the study with 500 participants (250 couples), as opposed to the original target of 1000 participants (500 couples). This sample size is achievable based on current recruitment rates and will maintain enough statistical precision for the 2x2 factorial design of the study. (full protocol available upon request)


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 1000
Est. completion date December 2022
Est. primary completion date December 2022
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 45 Years
Eligibility Inclusion Criteria: - Couple must have been in a new relationship that started no more than six months prior to study entry - Both partners plan on remaining in Montreal for at least 1 year - Plan on having continued sexual contact with partner - Be willing to comply with study procedures Exclusion Criteria: - Volunteers must not have been vaccinated against HPV-Gardasil-9 (both partners) - Any history of cervical, penile, oral or anal cancers - Being pregnant or plan on immediately becoming pregnant

Study Design


Intervention

Biological:
HPV vaccine, Gardasil 9
Once recruited, both individuals in a couple will be randomized independently to Gardasil 9 or placebo (Avaxim).
Hepatitis A vaccine
Provided by Sanofi Pasteur.

Locations

Country Name City State
Canada McGill University - Division of Cancer Epidemiology Montreal Quebec

Sponsors (1)

Lead Sponsor Collaborator
McGill University

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary The primary outcome will be the reduction of HPV DNA positivity for the target HPV vaccine types (i.e., HPVs 6, 11, 16, and 18) in multiple anatomic sites in the placebo-treated sexual partners of persons who received Gardasil. Reduction in HPV type concordance (for the four target types) will be the main outcome evaluable as per the above group contrasts. These comparisons will be done with due attention to the enrolment virological status of the individuals. For instance, it is expected that a Avaxim-treated woman who is positive for HPV 6 in the oral specimen but negative for this type in the vaginal specimen may derive benefit if her partner receives Gardasil, even if he is HPV-6 positive in the penile sample. The assumption is that protection via vaccination is pan-mucosal, via transudation of neutralizing antibodies; this protection may mediate transmission. At months 2, 4, 6, 9 and 12.
See also
  Status Clinical Trial Phase
Completed NCT05458869 - Evaluating the Human Papillomavirus Self-Collection Experience in Individuals Who Have Experienced Sexual Trauma
Completed NCT01932697 - Radiation Therapy and Docetaxel in Treating Patients With HPV-Related Oropharyngeal Cancer Phase 2
Completed NCT03265743 - HPV Vaccination in Women With Cystic Fibrosis N/A
Completed NCT00543543 - Broad Spectrum HPV (Human Papillomavirus) Vaccine Study in 16-to 26-Year-Old Women (V503-001) Phase 3
Recruiting NCT04226313 - Self-sampling for Non-attenders to Cervical Cancer Screening N/A
Completed NCT06199128 - Efficacy and Safety of Carboxymethyl Beta-glucan and Policarbophil in HPV Positive Patients
Terminated NCT01082861 - Efficacy and Immunomodulation Study of Simultaneous Human Papillomavirus/ Hepatitis B (HPV/HBV) Vaccination Phase 4
Unknown status NCT01087164 - Brief Interventions to Increase HPV Vaccine Acceptance in School-based Health Centers N/A
Completed NCT01265212 - Prevalence of Human Papillomavirus in Men Living in the Northern Plains N/A
Completed NCT00572832 - Randomized Trial of Alternative Quadrivalent Human Papilloma Virus (HPV) Vaccination Schedules in a University Setting N/A
Completed NCT03158220 - Immunogenicity and Tolerability of Broad Spectrum Human Papillomavirus (HPV) Vaccine in Adult and Young Adult Women (V503-004) Phase 3
Recruiting NCT05210348 - Clinical Evaluation of Detection of High Risk HPV in Urine
Completed NCT05680454 - A Phase I Trial Evaluate the Safety and Tolerability Profile of HPV Vaccine Phase 1
Completed NCT04133610 - HPVPro Study: Comparison of HPV Detection in Clinician-collected Cervical Swabs and Self-sampled Cervicovaginal Swabs N/A
Completed NCT00988884 - A Study of V503 Given Concomitantly With Menactra™ and Adacel™ in 11 to 15 Year Olds (V503-005) Phase 3
Not yet recruiting NCT05981807 - HPV Infection, Sexually Transmitted Infections and Anal Dysplasia in the Transgender Population
Recruiting NCT03302858 - A Safety and Efficacy Trial of Circumferential Anal Canal Radiofrequency Ablation for High-Grade Anal Intraepithelial Neoplasia Using the BARRX™ Anorectal Wand Phase 2
Completed NCT01694875 - Clinical Evaluation of the APTIMA® HPV 16 18/45 Genotype Assay on the PANTHER® System N/A
Completed NCT01205412 - An Observational Study on the Prevalence of Human Papillomavirus Types in Women in the Kingdom of Bahrain N/A
Completed NCT01158209 - An Observational, Epidemiological Study on the Prevalence of Human Papillomavirus Types in Women in Egypt N/A