A Study of RO5217790 in Participants With High Grade Cervical Intraepithelial Neoplasia (CIN) Associated With High Risk Human Papillomavirus (HR-HPV) Infection

A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Study of the Safety and Response Rate of 3 Subcutaneously Administered Doses of 5 X 10^7 PFU RO5217790 in Patients With High Grade Cervical Intraepithelial Neoplasia Grade 2 or 3 Associated With High Risk HPV Infection

This randomized, double-blind, placebo-controlled, parallel arm study will assess the safety and the efficacy of RO5217790 on histologic resolution in participants with high grade CIN associated with HR-HPV infection. Participants will be randomized to receive 3 subcutaneous injections of either placebo or RO5217790 on Days 1, 8, and 15. Study assessments will be made at Baseline, at Month 3 and 6, and every 6 months thereafter for an overall of 2.5 years.

Study Overview

• Status: Completed
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Drug: Placebo; Drug: RO5217790

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2020
  • Brussel, Belgium, 1090
  • Bruxelles, Belgium, 1070
  • Edegem, Belgium, 2650
  • Gent, Belgium, 9000
  • Leuven, Belgium, 3000
  • Tienen, Belgium, 3300
• Finland
  • Hus, Finland, 00029
  • Kuopio, Finland, 70211
  • Oulu, Finland, 90220
  • Tampere, Finland, 33520
• France
  • Bordeaux, France, 33076
  • Dijon, France, 21079
  • Nantes, France, 44093
  • Paris, France, 75231
  • Reims, France, 51092
  • Strasbourg, France, 67098
• Puerto Rico
  • San Juan, Puerto Rico, 00935
  • San Juan, Puerto Rico, 00909-1711
• Spain
  • Barcelona, Spain, 08036
  • Madrid, Spain, 28040
  • Madrid, Spain, 28942
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
  • Arizona
    • Phoenix, Arizona, United States, 85032
    • Phoenix, Arizona, United States, 85015
    • Tucson, Arizona, United States, 85712
    • Tucson, Arizona, United States, 85724-5078
  • California
    • Colton, California, United States, 92324
    • Los Angeles, California, United States, 90027
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
  • Connecticut
    • Stamford, Connecticut, United States, 06904
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
  • Florida
    • Lake Worth, Florida, United States, 33461
    • Miami, Florida, United States, 33136
    • Plantation, Florida, United States, 33324
    • Sarasota, Florida, United States, 34239
    • South Miami, Florida, United States, 33143
    • West Palm Beach, Florida, United States, 33409
  • Georgia
    • Atlanta, Georgia, United States, 30322
    • Augusta, Georgia, United States, 30912
    • Decatur, Georgia, United States, 30034
  • Louisiana
    • Marrero, Louisiana, United States, 70072
  • Massachusetts
    • Framingham, Massachusetts, United States, 01702
  • Missouri
    • Kansas City, Missouri, United States, 64139
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
  • Nevada
    • Las Vegas, Nevada, United States, 89128
    • Las Vegas, Nevada, United States, 89030
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
  • New York
    • Brightwaters, New York, United States, 11718
    • Bronx, New York, United States, 10461
  • North Carolina
    • New Bern, North Carolina, United States, 28562
    • Winston-salem, North Carolina, United States, 27103
  • Ohio
    • Englewood, Ohio, United States, 45322
    • Gallipolis, Ohio, United States, 45631
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
  • Pennsylvania
    • West Reading, Pennsylvania, United States, 19611
  • South Carolina
    • Columbia, South Carolina, United States, 29201
    • Greenville, South Carolina, United States, 29615
    • Myrtle Beach, South Carolina, United States, 29572
  • Tennessee
    • Nashville, Tennessee, United States, 37232
  • Texas
    • Austin, Texas, United States, 78705
    • Houston, Texas, United States, 77004
    • McAllen, Texas, United States, 78503
  • Utah
    • Sandy, Utah, United States, 84070
  • Virginia
    • Norfolk, Virginia, United States, 23502

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Have a diagnosis within 2 months prior to the first dose of RO5217790 of CIN 2/3 confirmed by colposcopy-directed punch biopsy; patients must have at least 1 quadrant of residual CIN2/3 disease remaining after biopsy. Entry to the trial will be allowed based on the local assessment of this criterion; however, CIN 2/3 diagnosis will have to be confirmed by the central pathologist for the purposes of analyzing the study
• Have satisfactory colposcopy, i.e. the entire acetowhite or disease area as well as the entire squamocolumnar junction visualized by colposcopy
• Have detection at screening of a single or multiple HR-HPV infection by analysis of liquid based cytology (LBC) material on the Roche Linear Array assay consistent with any of the trial strata as specified in study protocol

Exclusion Criteria:

• Have colposcopically visible CIN2/3 disease extending over more than 2 quadrants
• Have any anatomical condition of the cervix, including that resulting from previous cervical surgery, congenital malformation or other condition, that would interfere with a complete evaluation of the transformation zone and surveillance of CIN. If an endocervical curettage (ECC) is performed, and the endocervical curettings reveal CIN, patients are eligible as long as the endocervical lesion is directly extending from the primary lesion and is colposcopically visible in its entirety
• Have vulvar (VIN) or vaginal (VAIN) intraepithelial neoplasia
• Have atypical endometrial or glandular cells or evidence of carcinoma on biopsy
• Have a serious, concomitant disorder, including active systemic infection requiring treatment
• Have a prior history of or current malignancy other than adequately treated skin cancer (squamous cell cancer or basal cell carcinoma), unless the history of skin cancer is at the site of study treatment administration
• Have a proven or suspected immunosuppressive disorder or autoimmune disease
• Have any significant cardiac, hepatic or renal disease
• Have active viral infections including human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), cytomegalovirus (CMV), and Epstein barr virus (EBV) within 30 days of receiving study treatment. Mild viral infections such as Herpes Simplex Virus 1 (HSV-1) or common cold are not excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo matched to RO5217790 will be administered subcutaneously on Days 1, 8, and 15.	Drug: Placebo; Placebo matched to RO5217790 will be administered subcutaneously on Days 1, 8, and 15.
Experimental: RO5217790; RO5217790 will be administered at a dose of 5*10^7 plaque forming unit (pfu) subcutaneously on Days 1, 8, and 15.	Drug: RO5217790; RO5217790 will be administered at a dose of 5*10^7 pfu subcutaneously on Days 1, 8, and 15.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with CIN2/CIN3 associated with HPV16 single infection who achieved Histologic resolution (Defined as no CIN), determined by evaluation of tissue derived from surgical excision	Month 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants who achieved Histologic resolution (Defined as no CIN), determined by evaluation of tissue derived from surgical excision	Months 6
Percentage of participants who achieved Histologic response (Defined as CIN Grade less than [<] 2), determined by evaluation of tissue derived from surgical excision	Month 6
Percentage of participants with viral clearance based on Roche Linear assay results	Months 3 and 6
Percentage of participants with immunologic response to HPV antigens	Day 1 (predose), Days 8, 15, and 29, Months 3 and 6
Percentage of Participants with at least one Adverse Events (AEs)	Up to Month 30

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: November 20, 2009
• First Submitted That Met QC Criteria: November 27, 2009
• First Posted (Estimate): December 1, 2009

Study Record Updates

• Last Update Posted (Estimate): August 15, 2016
• Last Update Submitted That Met QC Criteria: August 11, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Cervical intraepithelial neoplasia; RO5217790
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia
• Other Study ID Numbers: NV25025; 2008-006946-24 (EudraCT Number)