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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Actinic Keratoses; Basal Cell Carcinoma; Squamous Cell Carcinoma
• Intervention / Treatment: Biological: HPV Vaccine; Biological: PLACEBO vaccine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Hovedstaden
    • Copenhagen, Hovedstaden, Denmark, 2400
      • Department of Dermatology, Bispebjerg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subjects who meet all the following criteria are eligible to participate in this study:

1. High AK burden, defined as ≥15 AK lesions in the included test area (50-100 cm2) at baseline
2. Test area does not involve the ala nasi, eyelids, nasolabial folds, or periauricular skin
3. >18 years of age at baseline
4. Fitzpatrick skin phototype I-IV
5. Legally competent, able to give verbal and written informed consent
6. 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.
7. 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:

1. Known or suspected immunosuppression (by disease or immunosuppressive drug)
2. History of vaccine-related allergic reactions or known allergy to Gardasil®9 ingredients or yeast
3. Previously vaccinated with any HPV vaccine
4. History of keloids
5. Other skin diseases present in the test area at baseline
6. Lactating or pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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
Long term Keratinocyte Carcinoma (KC) rates	Annual rate and total number of histologically confirmed KC lesions determined by assessment of electronic medical record/patobank results assessed 3, 5 and 10 years after vaccination compared to KC rates up to 5 years prior to vaccination	10 years

Collaborators and Investigators

• Sponsor: Merete Haedersdal
• Investigators: Principal Investigator: Merete Haedersdal, MD, PhD, DMSc, Bispebjerg Hospital; Principal Investigator: Emily Wenande, MD, PhD, Bispebjerg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2022
• Primary Completion (Actual): June 19, 2024
• Study Completion (Estimated): June 19, 2034

Study Registration Dates

• First Submitted: January 10, 2022
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Precancerous Conditions; Neoplasms, Basal Cell; Carcinoma; Carcinoma, Basal Cell; Keratosis, Actinic; Keratosis; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: EudraCT 2021-003895-15; H-21047863 (Other Identifier: National Committee on Health Research Ethics (NVK; Denmark))

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