Safety and Efficacy Study of Topical AP611074 Gel to Treat Genital Warts

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability and efficacy of the topical application of AP611074 5% gel during 6 weeks on ano-genital warts caused by human papillomavirus (HPV).

Detailed Description
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Genital warts (GW; also called condylomas or condylomata acuminata) are lesions caused by infection of Human papillomavirus (HPV)(specifically HPV-6 or HPV-11 types, found in > 95% of lesions). GW are sexually transmitted and affect about 1% of the sexually active population. GW represent a distressful condition for social and sexual life, especially in the cases of external condylomas. No HPV-specific antiviral treatment exists to date, and all existing therapies (either surgical or drug) have limited efficacy, with a significant level of GW recurrences and are associated with local skin reactions. AP611074 is a synthetic new chemical entity that is a potent and selective inhibitor of the interaction between two viral proteins from HPV6 and HPV11, an interaction that is a necessary step for HPV DNA replication and thus viral production. AP611074 is the first in class specific HPV antiviral described to treat condyloma caused by HPV infection.

Official Title
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A Double-blind, Placebo Controlled, Randomized, Phase IIa Study to Assess the Safety, Tolerability, Efficacy, and Pharmacokinetics of Repeated Topical Applications Over 42 Days of AP611074 5% Gel in Condyloma Patients

Conditions
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Anogenital Warts, Condylomata Acuminata, Human Papillomavirus Infection

Intervention / Treatment
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* Drug: AP611074
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Male or female patient aged between 18 and 55 years. External condylomas, 1-15 lesions, non-confluent and individually isolated. Lesions must not be internal (ie, they must not penetrate the urethral meatus, vagina or anal canal); their visualization must be complete by patients and investigators without major facilitation maneuvers and easily documented by digital pictures. Lesions should have a total surface smaller than 5 cm2, and an individual surface smaller than 1 cm2; lesions should be easily measured using a French Catheter Scale. Lesions to be treated should have appeared between 1-6 months before screening and patients should not have received any previous condyloma treatment since their appearance. For patients having previous episodes of condyloma lesions, they shouldn't have received any condyloma treatment for at least 12 months before screening. Main Exclusion Criteria: Patients with any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic or infectious disease that, in the Investigator's judgment, prevents the patients from participating to the study. Patients with VIN or PIN (intraepithelial neoplasia of vulva or penis; ie, Bowenoid papulosis), or genital disease (ie, lichen sclerosus, lichen planus, lichen simplex chronicus, dermatitis, psoriasis, bullous diseases, systemic diseases with genital manifestations) requiring treatment. Patients with fibroepithelial polyps or scaly non-viral papillomas, seborrheic keratosis, follicular papules, syringoma, or circumscribed lymphangiomas. Patients whose skin condition or coloration would interfere with the observation and the follow-up of the lesions during the study. Patients for whom a proper follow-up of the lesions during the study will not be possible, because of hair growth in the treatment area.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: AP611074 5% gel<br>Twice daily application of 100 mg dose of AP611074 5% gel for 41 days followed by a single morning application on Day 42 | Drug: AP611074<br> <br> * Other names: Anticondyloma drug;|
| Placebo Comparator: Placebo gel<br>Twice daily application of 100 mg dose of placebo gel for 41 days followed by a single morning application on Day 42 | Drug: Placebo<br>* Placebo gel manufactured to appear identical to AP611074 5% gel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete or partial regression of anogenital warts, based on the total lesion surface before and after treatment |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and local tolerability | Descriptive statistics will be calculated by comparing the number of subjects between Day 1 and Day 42 in each treatment group (active or placebo) presenting AEs, or changes in physical examination, vital signs (blood pressure and pulse rate), 12-lead ECG, clinical laboratory parameters (biochemistry, hematology, urinalysis), and local tolerability (erythema, scaling, stinging, oedema) | Up to 8 weeks | 
| Pharmacokinetic evaluation | Plasma concentrations of AP611074 will be measured from blood samples once weekly up to 8 weeks in all patients. Data will be summarized with descriptive statistics by nominal sampling time. | Up to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genital warts, Anogenital warts, HPV, Human papillomavirus, Antiviral