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

Phase 2

Completed

Conditions: Cervical Intraepithelial Neoplasia
Uterine Cervical Dysplasia

Interventions: Drug: placebo
Drug: A007

Registration Number: NCT00285207

Lead Sponsor: Tigris Pharmaceuticals

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 147

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	Placebo administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles.
A007	A007	0.25% A007 administered topically to the cervix via intravaginal applicator for 5 consecutive days of a 28-day cycle for 2 cycles.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (29): Visions Clinical Research-Tucson
🇺🇸
Tucson, Arizona, United States
Coastal Connecticut Research, LLC
🇺🇸
New London, Connecticut, United States
Washington Hospital Center
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Washington, District of Columbia, United States
Jersey Shore University Medical Center
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Neptune, New Jersey, United States
Northern California Research Corp
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Carmichael, California, United States
Mount Vernon Clinical Research, LLC
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Atlanta, Georgia, United States
Physician Care Clinical Research, LLC.
🇺🇸
Sarasota, Florida, United States
Medical College of Georgia
🇺🇸
Augusta, Georgia, United States
OB/GYN Specialists of the Palm Beaches
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West Palm Beach, Florida, United States
South Carolina Oncology Associates
🇺🇸
Columbia, South Carolina, United States
Greater Cincinnati OB/GYN, Inc.
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Cincinnati, Ohio, United States
Hope Research Institute, LLC
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Phoenix, Arizona, United States
IGO Medical Group of San Diego
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San Diego, California, United States
University of Alabama Highlands, Dept. of OB/GYN
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Birmingham, Alabama, United States
Office of R. Garn Mabey, MD
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Las Vegas, Nevada, United States
Planned Parenthood of Houston & Southeast Texas, Inc.
🇺🇸
Houston, Texas, United States
East Jefferson OB/GYN
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Metairie, Louisiana, United States
Global OB/GYN Centers of Florida
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Pembroke Pines, Florida, United States
Visions Clinical Research
🇺🇸
Boynton Beach, Florida, United States
Montefiore Medical Center-Weiler Division Dept of OB/GYN & Women's Health
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Bronx, New York, United States
New York Downtown Hospital
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New York, New York, United States
Lehigh Valley Hospital
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Allentown, Pennsylvania, United States
Magee-Womens Hospital, Dept of OB/GYN & Reproductive Services
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Pittsburgh, Pennsylvania, United States
Hill Country OB/GYN
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Austin, Texas, United States
Jacobi Medical Center
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Bronx, New York, United States
Arrowhead Regional Medical Center
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Colton, California, United States
Robin Black OGNP
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Costa Mesa, California, United States
University of Oklahoma Health Sciences Center Dept of OB/GYN
🇺🇸
Oklahoma City, Oklahoma, United States
4601 Old Shepard Place; Bldg 2, Suite 201
🇺🇸
Plano, Texas, United States