Cervical Intraepithelial Neoplasia, Uterine Cervical Dysplasia
Conditions
Keywords
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)
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.
Interventions
DRUGplacebo
5 days of 28 day cycle for 2 cycles
DRUGA007
5 days of 28 day cycle
Sponsors
Tigris Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (no treatment) | 70 |
| A007 Experimental A007 | 77 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | non-compliance | 0 | 1 |
| Overall Study | Pregnancy | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | A007 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 77 Participants | 70 Participants | 147 Participants |
| Age Continuous | 28.7 years STANDARD_DEVIATION 7.9 | 28 years STANDARD_DEVIATION 6 | 28.4 years STANDARD_DEVIATION 7.1 |
| Region of Enrollment United States | 77 participants | 70 participants | 147 participants |
| Sex: Female, Male Female | 77 Participants | 70 Participants | 147 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 63 | 5 / 75 |
| serious Total, serious adverse events | 0 / 63 | 0 / 75 |
Outcome results
Primary
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.
Time frame: baseline and 4 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Pathological Response | 20 participants |
| A007 | Pathological Response | 24 participants |
Secondary
Eradication of Human Papilloma Virus (HPV) Will be Assessed by Way of Cervical Cytology and Swab Collection.
Time frame: over the course of the trial
Secondary
Immunologic Parameters B/T Cells Will be Assessed by B/T Cell Profile Collection.
Time frame: over the course of the trial
Secondary
Local Tolerability and Systemic Safety of A-007 Will be Assessed by Way of CTCAE 3.0.
Time frame: over the course of the trial