Safety and Efficacy of A-007 Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix

Study Overview
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Brief Summary
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A-007 is an investigational therapy which may be effective in the treatment of pre-cancerous cervical dysplasia (abnormal cell growth). The purpose of this study is to evaluate the safety and efficacy of A-007, when used to treat high-grade cervical dysplasia.

Detailed Description
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This is a randomized, double-blind, placebo-controlled study. It will randomize patients in a 1:1 ratio to topical cervical treatment with A-007, or placebo gel. Following biopsy confirmation of High Grade Squamous Intraepithelial Lesions (HSIL), women will treat themselves with gel applied to the cervix via an intravaginal applicator. Patients will apply gel once daily for 5 consecutive days of a 28-day cycle for 2 cycles. Women will return to clinic for safety assessments, colposcopy, cytology, and virologic and immunologic testing.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Trial of the Use of 4,4'-Dihydroxybenzophenone-2,4-Dinitrophenyl-hydrazone (A-007) Topical Gel in the Treatment of High-Grade Squamous Intraepithelial Lesions (HSIL) of the Cervix

Conditions
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Cervical Intraepithelial Neoplasia, Uterine Cervical Dysplasia

Intervention / Treatment
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* Drug: placebo
* Drug: A007


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients may be enrolled in the study only if they meet all of the following criteria: 18 years of age or older The patient or her authorized representative must sign and date an Ethical Review Board-approved informed consent document. All aspects of the protocol must be explained and written informed consent obtained. Patients must have histological proof of HSIL (CIN 2/3) disease documented. Cervical swabs must test positive for HPV (by Hybrid Capture 2). Patients must have a Hb ≥ 9 g/dl, a peripheral WBC ≥ 3000 mm3 and platelet counts ≥ 100,000 mm3. Normal hepatic and renal functions - AST and ALT < 2.5 x ULN and creatinine < 1.5 x ULN, respectively. Females of childbearing potential must use one of the following birth control methods during the treatment period and 2 weeks thereafter: oral, implantable, injectable contraceptives; abstinence (celibacy). Contraceptive sponges, IUD, spermicides, sponges, condoms, or partner's vasectomy are not acceptable methods of birth control. Exclusion Criteria: Patients will be excluded from the study for any of the following preexisting reasons: Patients with LSIL (CIN 1) or invasive squamous cell carcinoma (SCC). SIL (CIN) involving the endocervix as determined by endocervical curettage, or otherwise not amenable to adequate colposcopic follow-up evaluations, i.e. unsatisfactory colposcopy. CIN 3 involving more than two cervical quadrants on colposcopy. Patients treated for cervical SIL within the past year. Patients with other malignancy (except for non-melanoma skin) within the past 5 years. Patients with any active infections (including HIV) other than HPV. Patients with known clinically relevant immunological deficiency. Concurrent treatment with cytotoxic, radiation, or immuno-stimulative therapy, or with systemic corticosteroids at a dose of > 5 mg/d of prednisone (or its equivalent). Participation in another investigational medication trial concurrently or within 30 days, or prior participation in an HPV vaccine trial. Treatment within the last 30 days with a medication that has not received regulatory approval at the time of study entry. Concomitant use of topical vaginal medications. Significant acute or chronic medical or psychiatric illness that, in the judgment of the Investigator, could compromise subject safety, limit the subject's ability to complete the study, and/or compromise the objectives of the study. History of allergy or hypersensitivity to cosmetics, toiletries, or other topical or dermatologic products. Pregnant or lactating females who are nursing and will not consent to cease nursing. Investigators, site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles. | Drug: placebo<br>* 5 days of 28 day cycle for 2 cycles<br>|
| Experimental: A007<br>0.25% A007 administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles. | Drug: A007<br>* 5 days of 28 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Response | Pathological resonse is defined as a patient who regressed from Cervical intraepithelial neoplasia (CIN) 2/3 to normal at the end of 4 months. | baseline and 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Tolerability and Systemic Safety of A-007 Will be Assessed by Way of CTCAE 3.0. |  | over the course of the trial | 
| Eradication of Human Papilloma Virus (HPV) Will be Assessed by Way of Cervical Cytology and Swab Collection. |  | over the course of the trial | 
| Immunologic Parameters B/T Cells Will be Assessed by B/T Cell Profile Collection. |  | over the course of the trial | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical Intraepithelial Neoplasia (CIN), High-grade Cervical Intraepithelial Neoplasia, High-grade Squamous Intraepithelial Lesions (HSIL), Human Papilloma Virus (HPV), High-Grade Cervical Intraepithelial Lesions (CIN 2/3)