Efficacy of Quadrivalent HPV Vaccine to Prevent Relapses of Genital Warts After Initial Therapeutic Response

NCT03296397 | Unknown Phase 3 DMC

• 1 other identifier: P150957
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

External genital warts (EGW) are a frequent disease (typical yearly incidence of 100 to 200 new cases per 100.000 person-years, typical prevalence of 1 to 4% of the sexually active population), with a heavy toll on patients' quality of life: low self-esteem and severe impairment of sexual well-being are common consequences. Treatments are painful and take time to achieve cure because of low complete remission (20 to 60%) and high recurrence rates (10 to 40%, 30% on average). Finding new means to reduce these recurrence rates thus seems justified. Infection with Human Papillomavirus (HPV) is responsible for EGW,other warts and some epithelial cancers. Out of two currently available HPV vaccines (Cervarix and Gardasil®), only Gardasil® is " quadrivalent " i.e. contains virus like particles imparting protection versus 4 genotypes of HPV, 2 of them responsible of most cancers and pre cancers of the cervix (HPV 16 and 18), and 2 for 90% of EGW (HPV 6 and 11). A close to 100 % efficacy of the quadrivalent HPV vaccine (QHV) on prevention of EGW in naive patients has been shown, leading to their near disappearance in the vaccinated population of countries with a good vaccine coverage. Beside this preventive efficacy, literature data also show that HPV vaccines have an up-to-100% protective effect versus recurrence of destroyed precancerous lesions of the cervix in non-naive patients with an up-to-40 month's follow-up. Also, there is anecdotal evidence that they could help treat severe wart conditions. QHV is also safe and well tolerated when used in a preventive manner. Investigator hypothesis is that QHV could have a protective effect on the recurrence of EGW in patients who achieve complete remission. The primary objective is to evaluate if the HPV vaccine, as compared to placebo, reduces the relapse rate of external genital warts over a 12 month-period after their first injection. The primary endpoint is the Relapse-free "survival". Relapse will have to be clinically confirmed. The secondary objectives are : 1. To assess the improvement of the quality of life of the patients 2. To investigate the clinical tolerance to three doses of HPV vaccine. The secondary endpoints are

• Group 1: Gardasil (at M0) + Gardasil (at M2) + Gardasil (at M6)
• Group 2: Placebo (at M0) + Placebo (at M2) + Placebo (at M6) Subjects meeting all the inclusion criteria and none of the exclusion criteria will be vaccinated by the investigator or designee of the investigational center and will be examined by the investigator or designee 30 minutes post immunization to assess for local and systemic reactions. All subjects will be followed by the investigators or designee during the study by phone contacts and visits on site. Diary cards will be used after each vaccination to follow the patients. Number of visits /participant: 9 Schedule of visits : 1 selection visit (V0) , 3 vaccinations scheduled on site at M0, M2 and M6, 3 phone contacts at M1, M3 and M7, 2 clinical follow up visits on site at M9 and M12 + 1 unscheduled visit on site in case of EGW relapse during the study

Conditions

Genital Warts

Keywords

Genital warts; HPV vaccine; Relapse

Outcome Measures

Primary Outcomes (1)

• Relapse free survival (days from first injection)

  up to 12 months

Secondary Outcomes (4)

• Improvement of quality of life by Dermatology Life Quality Index (DLQI) validated scale

  at each planned visit/phone contact (1, 2, 3, 6, 7, 9 months), at 12 months (upon end of study visit) or upon premature withdrawal visit

• Improvement of quality of life by CECA validated scale

  at each planned visit/phone contact (1, 2, 3, 6, 7, 9 months), at 12 months (upon end of study visit) or upon premature withdrawal visit

• Clinical tolerance of QHV (percentage of patients with AE)

  Day 0

• Clinical tolerance of QHV

  Month 2 and Month 6

Study Arms (2)

HPV Quadrivalent vaccine (QHV)

ACTIVE COMPARATOR

Gardasil

Biological: Vaccination with Gardasil

Placebo

PLACEBO COMPARATOR

Normal Saline

Biological: Injection of Normal Saline

Interventions

Vaccination with Gardasil BIOLOGICAL

Vaccination with Gardasil in patients apparently cured of external genital warts

HPV Quadrivalent vaccine (QHV)

Injection of Normal Saline BIOLOGICAL

Injection of Normal Saline in patients apparently cured of external genital warts

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 years and older;
• Patients who, after the nature of the study has been explained to them, and prior to any protocol specific procedures being performed, have given written consent according to local regulatory requirements
• Women of childbearing potential must have a negative pregnancy test and an effective contraception from selection visit (V0) and up to the end of the vaccination period of 6 months;
• Males must have an effective contraception with condoms from selection visit (V0) and up to the end of the vaccination period of 6 months;
• Patients affiliated to a social security regimen;
• Patients able to participate during the 12 months of the study.

You may not qualify if:

• Patients with diagnosis of internal ano-genital warts (intra rectal, intra vaginal, intra urethral) at the selection visit
• Patients with positive HIV, Hepatitis C virus (HCV) or Hepatitis B virus (HBV) (Ag HBS) tests;
• Patients whose regular partner(s) have active uncontrolled clinical EGW;
• Patients who received the HPV Vaccine at any time before enrolment to the study;
• Any serious chronic or progressive disease according to the judgement of the investigator;
• Patients with history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system, or under immunosuppressive therapy including use of systemic corticosteroids or chronic immunosuppressant medication (more than 14 days) (i.e. prednisone, or equivalent ≥10 mg/day) within :
• Patients with history of known allergies/hypersensitivity to any component of study vaccine;
• Patients who have any malignancy or lymphoproliferative disorder;
• Patients with thrombocytopenia or coagulation disorder/treatment contra-indicating intramuscular injection;
• Women who are pregnant or are breast-feeding, or are of childbearing age who do not use or do not plan to use acceptable birth control measures, during the first 6 months of the study ;
• Male who do not use or do not plan to use condoms during the first 6 months of the study;
• Patients under a measure of legal protection or unable to consent;
• Patients participating in any clinical trial with another investigational product 28 days prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Hôpital St Louis

Paris, 75010, France

RECRUITING

GH Cochin - Broca - Hôtel-Dieu,

Paris, 75679, France

NOT YET RECRUITING

MeSH Terms

Conditions

Condylomata Acuminata; Recurrence

Interventions

Vaccination; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

Condition Hierarchy (Ancestors)

Papillomavirus Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Warts; Skin Diseases, Viral; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunotherapy, Active; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Primary Prevention; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Communicable Disease Control; Public Health Practice; Public Health; Environment and Public Health; Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Papillomavirus Vaccines; Viral Vaccines

Study Officials

• Sebastien FOUERE, MD, MSc

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sebastien FOUERE, MD, MSc

CONTACT

(0)1 42 49 99 24; sebastien.fouere@aphp.fr

Olivier CHOSIDOW, MD, PhD

CONTACT

(0)1 49 81 25 01; olivier.chosidow@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2017
• First Posted: September 28, 2017
• Study Start: November 15, 2017
• Primary Completion: March 1, 2020
• Study Completion: April 1, 2020
• Last Updated: February 27, 2018

Record last verified: 2017-07

Locations

FR (2)