Nonavalent HPV Vaccine in the Treatment of Difficult-to-treat Palmo-plantar Warts

Study Overview
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Brief Summary
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Cutaneous viral warts are very common and are caused by the human papilloma virus (HPV). Most people experience warts in one form or another at some point in their lives. Cutaneous warts are related to different types of HPV. For the palms and soles, HPV 2 has been the most frequently found but HPV 1, 4, 27, and 57 have also been described. Our hypothesis is that vaccination by nonavalent vaccine against HPV could lead to a complete resolution of difficult-to-treat palmo-plantar warts patients of more than 15 years and 3 months of age.

Detailed Description
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The qHPV and nHPV has been used as a therapeutic approached for the treatment of cutaneous warts in case reports and some case series. Very recently, the Journal of the American Academy of Dermatology (JAAD)-the journal with the highest impact factor in the dermatological field- has published a review of all the cases reported in the scientific literature. The authors were strongly in favor of the use of the vaccine in case of difficult-to-treat warts and have highlighted the need for clinical trials. In the literature, 80 patients have been described with cutaneous warts treated by qHPV or nHPV with more than 50% of efficacy.Our hypothesis is that vaccination by nonavalent vaccine against HPV could lead to a complete resolution of difficult-to-treat palmo-plantar warts patients of more than 15 years and 3 months of age.

Official Title
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Efficacy of the Nonavalent HPV Vaccine in the Treatment of Difficult-to-treat Palmo-plantar Warts

Conditions
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Palmar or Plantar Warts

Intervention / Treatment
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* Biological: Vaccination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of age ≥ 15 years and 3 months with palmar or plantar warts since more than one year with: ≥ 5 warts (X palmar and X plantar) or ≥ 4 cm2 of Total surface involved by the warts (Y cm x Z cm). Patients should have received two lines of treatment during the past year before inclusion, the last treatment must be at 3 weeks maximum before inclusion: At least one months of application of topical salicylic acid At least two sprays of liquid nitrogen Painful warts (VAS ≥ 4) or functional discomfort (Revised foot function index (RFFI) or Cochin Hand Function Scale (CHSF) or social discomfort (DLQI)). No topical or systemic immunosuppresive/ immunomodulating drugs Women of childbearing potential must have a negative pregnancy test and an effective contraception (V1) and up the end of the vaccination period of 6 months; Individuals affiliated to a social security regimen; Individuals able to participate and to follow up during the study period. Exclusion Criteria: Recent (under 72 hours) Positive Covid test (PCR) Any causes of immunosupression: organ transplant recipients, bone-marrow transplantation, immunosupressive regimens for any diseases, HIV positivity. Women or men who received HPV Vaccine previously of the study; Any serious chronic or progressive disease according to the judgement of the investigator; Individuals with history of known allergies/hypersensitivity to any component of study vaccine; Individuals who have any malignancy or lymphoproliferative disorder; Individuals with thrombocytopenia or coagulation disorder contre-indicating intramusculary injections; Patient with anticoagulant therapy Individuals with body temperature > 38.0 degrees Celsius or/and acute disease within 3 days of intended study vaccination; Women who are pregnant or are breast-feeding, or are of childbearing age who have not used or do not plan to use acceptable birth control measures, during the first 6 months ½ of the study; Individuals under a measure of legal protection or unable to consent; Individuals 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 the study. Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants, if applicable Patient on AME (state medical aid) (unless exemption from affiliation). Patient wishing to be vaccinated with Gardasil 9® within 6 months or refusing the principle of postponing vaccination. Immunosuppressive therapy including use of systemic corticosteroids or chronic immunosuppressant medication (more than 14 days)

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter national clinical trial, phase III, two parallel group randomized (in a 1:1 ratio)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gardasil 9®<br>Nonavalent HPV vaccine | Biological: Vaccination<br>* Intramuscular injections of 0,5 ml will be administered at M0, M2 and M6<br>|
| Placebo Comparator: Placebo<br>NaCl 0.9 % solution for injection | Biological: Vaccination<br>* Intramuscular injections of 0,5 ml will be administered at M0, M2 and M6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission of cutaneous warts | Complete remission of cutaneous warts 7 months after the first injection of the vaccine | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life evaluated | Quality of Life will be evaluated with QoL Questionnaire (DLQI) | Inclusion, 2 months, 6 months, 7 months | 
| Pain (VAS) | Pain will be assess using VAS | Inclusion, 2 months, 6 months, 7 months | 
| Functional discomfort for walking and functional disability in hands | Functional discomfort for walking and functional disability in hands will be evaluated using the Revised Foot Function index or Cochin hand function scale respectively at M0, M2, M6, M7. | Inclusion, 2 months, 6 months, 7 months | 
| Partial remission of cutaneous warts | Partial remission of cutaneous warts 7 months after the first injection of the vaccine. | 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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WARTS, Vaccine HPV