Intralesional Gardasil-9 for the Treatment of Recalcitrant Warts

A Randomized, Double-Blind, Placebo-Controlled Trial of Intralesional Gardasil-9 Vaccine for the Treatment of Recalcitrant Verrucae

This study will evaluate whether Gardasil-9, a vaccine normally used to prevent human papillomavirus (HPV) infection, may be effective for treating recurring warts that have not responded to standard treatments. In this study, Gardasil-9 will be injected directly into a wart rather than into a muscle, which is an investigational use of the vaccine. Participants will be randomly assigned to receive injections of either Gardasil-9 or sterile saline (placebo) directly into a wart. Neither the participant nor the clinician administering the injection will know which treatment is being given. The study will evaluate participants during treatment and follow-up visits to assess their warts and quality of life.

This is a randomized, double-blind, placebo-controlled study evaluating the use of intralesional Gardasil-9 for the treatment of recalcitrant verrucae. Gardasil-9 is approved by the U.S. Food and Drug Administration (FDA) for the prevention of disease caused by certain types of human papillomavirus (HPV) and is typically administered by intramuscular injection. In this study, Gardasil-9 will be injected directly into warts as an investigational treatment for warts that have not responded to standard therapies.

Eligible participants will be adults with at least one wart that has failed to resolve after two standard therapies. Examples of prior therapies may include cryotherapy, electrodesiccation, salicylic acid, or over-the-counter treatments. Participants must be healthy and not immunocompromised.

Participants will be randomized in a 2:1 ratio to receive either intralesional Gardasil-9 or sterile saline placebo. Two-thirds of participants will be assigned to Gardasil-9 and one-third will be assigned to placebo. The study coordinator will prepare the assigned treatment in a separate location so that both the participant and the clinician administering the injection remain blinded to treatment assignment.

At the initial treatment visit, study investigators will confirm that the participant has at least one wart that has failed two or more previous treatments. Photographs will be taken to document the participant's warts before treatment. Participants will also complete the Dermatology Life Quality Index (DLQI) to assess the impact of their skin condition on their quality of life. The participant may select the wart or warts to be treated, and up to three warts may be injected during a treatment visit. The study clinician will inject the assigned study treatment, either Gardasil-9 or sterile saline, directly into the selected wart or warts. Participants may elect to receive lidocaine for local anesthesia prior to administration of the study treatment.

Following treatment, a member of the study team will contact the participant within approximately one week to assess any reported changes to the treated wart or warts or any new reactions. Participants will return for an in-person follow-up visit approximately 4-6 weeks after treatment. At the follow-up visit, photographs will again be taken to document the warts. If the treated wart or warts have not resolved or have only partially resolved, additional treatment may be administered. Participants will return approximately 4-6 weeks later for further evaluation and may receive a third treatment if the wart or warts have not resolved. At the completion of the blinded treatment period, participants will complete the DLQI again and will be informed whether they received Gardasil-9 or sterile saline.

After completion of the blinded portion of the study, participants who were assigned to sterile saline will have the opportunity to receive intralesional Gardasil-9 during an open-label extension. Participants initially assigned to Gardasil-9 whose warts have not completely cleared after the initial treatment period may also continue to receive additional Gardasil-9 injections during the open-label extension. Participants may receive up to six total treatments at approximately 4-6 week intervals as part of the study and open-label extension.

Inclusion Criteria:

• Age 18 years or older.
• Immunocompetent (no history of organ transplantation, active malignancy requiring immunosuppressive therapy, or HIV positive status)
• At least one wart that has been refractory to treatment
• At least two treatment modalities failed, including but not limited to:

cryotherapy, electrodessication, keratolytic agents, bleomycin, salicylic acid, excision.

Exclusion Criteria:

• Unable to provide informed consent.
• Younger than 18 years of age.
• Pregnant.
• Prisoner.
• Vulnerable populations, including immunocompromised status (active cancer, active TB - latent or previous history of these would not exclude patients)
• Previous severe reaction to HPV vaccination or known allergy to any vaccine component.