Impact of Human Papillomavirus (HPV) Vaccination on Burden of Disease in Patients With Actinic Keratosis

Study Overview
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Brief Summary
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A double-blind, randomized, placebo controlled intervention trial on patients with actinic keratosis.

Detailed Description
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Endeavoring to develop a new therapeutic and preventative strategy for patients with AK, this study aims to investigate the impact of 9-valent HPV vaccination on AK burden and -development over the course of 12 months. Seventy actinic keratosis (AK) patients are randomized 1:1 to two parallel groups that receive blinded HPV vaccination or sham placebo (isotonic NaCl) vaccination at baseline (day 0), month 2 and month 6. At month 6 and 9, both groups undergo lesion-directed cryotherapy of Olsen grade II-III AKs. Treatment response, based on percentage change (%) in baseline number of AK lesions in a predefined test area (primary outcome), is evaluated at months 2, 6, 9, and 12.

Official Title
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Impact of Human Papillomavirus (HPV) Vaccination on Burden of Disease in Patients With Actinic Keratosis - a Double-blind Randomized Controlled Trial

Conditions
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Actinic Keratoses, Basal Cell Carcinoma, Squamous Cell Carcinoma

Intervention / Treatment
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* Biological: HPV Vaccine
* Biological: PLACEBO vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who meet all the following criteria are eligible to participate in this study: High AK burden, defined as ≥15 AK lesions in the included test area (50-100 cm2) at baseline Test area does not involve the ala nasi, eyelids, nasolabial folds, or periauricular skin >18 years of age at baseline Fitzpatrick skin phototype I-IV Legally competent, able to give verbal and written informed consent Subject is willing to participate and can comply with protocol requirements including the refraining from other therapy (with the exception of KC treatment) in the test area for the duration of the trial. Women of childbearing potential1 must be confirmed not pregnant by a negative urine pregnancy test prior to trial treatment and be on effective contraception2 until discontinuation of the vaccine therapy. Additional pregnancy testing will not be conducted unless pregnancy is suspected. 1Female subjects are considered of childbearing potential unless they have been hysterectomized or have undergone tubal ligation or have been post-menopausal for at least one year prior to first visit. 2Intrauterine device or hormonal contraception (oral, implant, patch, vaginal ring, injection). Exclusion Criteria: Subjects meeting any of the following criteria are not eligible to participate in this study: Known or suspected immunosuppression (by disease or immunosuppressive drug) History of vaccine-related allergic reactions or known allergy to Gardasil®9 ingredients or yeast Previously vaccinated with any HPV vaccine History of keloids Other skin diseases present in the test area at baseline Lactating or pregnant women

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HPV vaccine<br>Commercially available nonavalent HPV vaccine (Gardasil(R) 9) given intramuscularly at baseline, month 2 and month 6 | Biological: HPV Vaccine<br>* (Gardasil 9 human papilloma vaccine)<br>|
| Placebo Comparator: Isotonic Saltwater Vaccine<br>0.9% NaCl given intramuscularly at baseline, month 2 and month 6 | Biological: PLACEBO vaccine<br>* Isotonic saltwater sham vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response in HPV vaccinated versus control group | Percentage change from baseline (%) in number of AK lesions (grades I and II-III) in the selected test area | Evaluated at month 2, 6, 9, and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New AK lesions | New AK lesions (n) arising in the test area since last visit | Evaluated at month 2, 6, 9, 12 | 
| Partial (≥75%) clearance | Atleast 75 % reduction in total number of AK lesions compared to baseline | Evaluated at month 12 | 
| Complete (100%) clearance | 100% reduction in total number of AK lesions compared to baseline | Evaluated at month 12 | 
| Side Effects | Occurence of local and systemic side effects in HPV vaccinated versus control group | Evaluated over the course of 12 months | 
| New Keratinocyte Carcinomas (KCs) | New KCs (basal or squamous cell carcinoma) identified anywhere on the body of participants in HPV vaccinated versus control group registered over the course of the 12-month trial, compared to average yearly whole-body KC rate (determined by assessment of electronic medical record/patobank results) up to 3 years prior to baseline. | Evaluated at month 2, 6, 9, and 12 |