Clinical trial NCT00312286: Efficacy of 851B Gel for Treating High-Risk Cervical Human Papillomavirus Infection in Women.
Official title: A Randomized, Placebo-Controlled Phase II Study of Multiple Dosing Regimens of Intravaginally Administered 851B Gel for the Treatment of Cervical High Risk HPV Infection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Papillomavirus Infections
Keywords: Cervical Neoplasms
Drug Therapy
Human Papillomavirus
Cervical Human Papillomavirus
Cervical Dysplasia
Chemoprevention
High Risk Cervical Human Papillomavirus
Atypical Squamous Cells of Undetermined Significance
Low Grade Intraepithelial Lesions
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2006-04-10
Enrollment: 538
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate efficacy of 851B gel over a range of concentrations and dosing regimens on high-risk cervical human papillomavirus infection in women.

Detailed description: Cervical cancer is caused by infection with specific genotypes of the human papillomavirus referred to as oncogenic or high-risk human papillomavirus. Current epidemiologic evidence suggests that 80% of sexually active women will become infected during their lifetime with human papillomavirus and 50% of these infections will be due to high-risk human papillomavirus. With US annual rates of cervical cancer now in the range of 13,000/year, a very substantial number of women are left with uncertainty regarding whether their infection will clear spontaneously or progress to cancer.

Subjects participating in this study were required to visit the clinic for approximately 15 or 16 visits, and maintain a diary of self-dosing and menstruation cycles. The total time of participation in this study was approximately 27 months.

Eligibility criteria: Inclusion Criteria:

* A female subject of childbearing potential who is sexually active using contraception.
* Subject is willing to abstain from all sexual contact involving her genitalia for at least 24 hours prior to and 24 hours after study drug administration.
* Subject must be neither pregnant nor lactating from Screening throughout the duration of the study.
* Subject has 1 of the following:

  * Menstruating with a stable cycle and has at least 21 non-bleeding days.
  * Amenorrheic (due to injectable or extended-cycle contraceptives).
* Subject is willing to refrain from using vaginal douche products during the treatment period and through the Follow-up Month 4 visit.
* Subject has a Pap test interpretation of either low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance.
* Subject has a uterine cervical sample that is high-risk human papillomavirus positive.

Exclusion Criteria:

* The Subject has evidence of an uncontrolled, clinically significant medical condition as determined by the investigator.
* The Subject has a history of hemorrhagic diatheses or coagulopathy.
* The Subject has a history of toxic shock syndrome.
* The Subject has received any of the following medications in the timeframes listed below:

  * 851 (in any form) or an active (non-placebo) human papillomavirus vaccine at any time prior to the screening visit.
  * In the 4 weeks prior to the screening visit the subject has received:

    * Interferon therapy or other therapies that promote a proinflammatory immune state, including:

      * immunomodulators.
      * cytotoxic drugs.
      * drugs known to have major organ toxicity.
    * Used a vaginal douche 72 hours prior to the screening visit.
    * Received any investigational drug within 60 days of Study Day 1.
    * Used in the 2 weeks prior to Study Day 1:

      * oral or inhaled corticosteroids (\>1000 mcg/day, fluticasone propionate \>600 mg/day, or equivalent).
      * systemic steroids.
      * topical drugs to the anogenital area.
      * NuvaRing.
* The Subject has a history of hypersensitivity to any components of the gel formulation or to iodine.
* The Subject has given birth or has had a spontaneous or induced abortion within 2 months of Study Day 1.
* The Subject uses an intrauterine device, diaphragm, NuvaRing, or additional contraceptive foam or gel for birth control.
* The Subject has:

  * histology read as high-grade cervical intraepithelial neoplasia.
  * cytology read as high-grade squamous intraepithelial lesion.
  * cytology read as atypical glandular cytological abnormalities.
  * cytology read as atypical squamous cells - cannot exclude high grade.
  * cervical carcinoma of any type.
  * apparent endocervical involvement.
  * high-grade vulvar intraepithelial neoplasia.
  * high-grade vaginal intraepithelial neoplasia.
* If the limits of a cervical lesion cannot be readily visualized.
* If the limits of the transformation zone cannot be readily visualized.
* The subject has clinical evidence of a vaginal infection or sexually transmitted infection, other than cervical human papillomavirus infection at the Study Day 1 visit.
* The Subject has had a cervical biopsy within 1 month prior to the screening visit.
* The Subject has had any previous ablative or surgical treatment of the cervix within 3 months prior to the screening visit;
* The Subject has a history of alcoholism or substance abuse within 1 year or has current alcohol or substance abuse as assessed by the investigator.
* The Subject has tested positive for human immunodeficiency virus at the screening visit or has evidence of any other immunosuppressive disease.

Primary outcomes:
measure: Time to clearance of high-risk human papillomavirus infection.
timeFrame: At each visit
Secondary outcomes:
measure: Proportion of subjects with evidence of regression to normal cytology.
timeFrame: Screening Visit and Follow-up Visits (Months 6, 8, 14, 20, and 26).
measure: Proportion of subjects with improvement in cervical lesions as rated by the investigator (measured by colposcopy).
timeFrame: At each visit
measure: Proportion of subjects who develop histological evidence of cervical intraepithelial neoplasia.
timeFrame: Visits 1-3 as assigned by group
measure: Time to progression of disease to precancer.
timeFrame: Visits 1-3 as assigned by group
measure: Change in relative light units ratios relative to the positive control from Hybrid Capture 2® assay (semi-quantitatively assessing viral load).
timeFrame: At each visit
Other outcomes:
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city: Decatur
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city: Woodstock
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city: Idaho Falls
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city: Iowa City
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city: Louisville
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city: Detroit
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state: Michigan
city: Paw Paw
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city: Chaska
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state: Minnesota
city: St. Louis
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state: Missouri
city: Las Vegas
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state: Nevada
city: Reno
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state: Nevada
city: Lebanon
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state: New Hampshire
city: Newark
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state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Bronx
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state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: New Bern
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Bismark
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state: North Dakota
city: Fargo
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state: North Dakota
city: Gallipolis
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state: Ohio
city: Oklahoma City
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state: Oklahoma
city: Eugene
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state: Oregon
city: Medford
country: United States
state: Oregon
city: Erie
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state: Pennsylvania
city: Philadelphia
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state: Pennsylvania
city: Pittsburg
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state: Pennsylvania
city: Pottstown
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state: Pennsylvania
city: West Reading
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state: Pennsylvania
city: Wynnewood
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state: Pennsylvania
city: Columbia
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state: South Carolina
city: Greenville
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state: South Carolina
city: Watertown
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state: South Dakota
city: Bristol
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city: Chattanooga
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city: Clarksville
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state: Tennessee
city: Memphis
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city: Nashville
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city: Austin
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city: Carrollton
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city: Dallas
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city: Houston
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city: Plano
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state: Texas
city: San Antonio
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state: Texas
city: Sandy
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state: Utah
city: Richmond
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state: Virginia
city: Virginia Beach
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state: Virginia
city: Renton
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state: Washington
city: Seattle
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state: Washington
city: Winnipeg
country: Canada
state: Manitoba
city: Ottawa
country: Canada
state: Ontario
city: Quebec
country: Canada
city: Toronto
country: Canada
city: Rio Piedras
country: Puerto Rico
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: