High grade cervical intraepithelial neoplasia grade 2 or 3 associated with High Risk HPV infection MedDRA version: 9.1 Level: LLT Classification code 10049701 Term: Cervical intraepithelial neoplasia II MedDRA version: 9.1 Level: LLT Classification code 10049702 Term: Cervical intraepithelial neoplasia III
Conditions
Interventions
Product Name: HPV targeted immunotherapy
Product Code: RO5217790
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: not defined yet
Current Sponsor code: RO5217790
Other descriptive na
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Are greater than or equal to 18 years old 2. Have provided written informed consent 3. Have a negative serum pregnancy test at screening 4. Use effective contraception for the first 6 months of the study; 2 methods of contraception, one of which must be barrier, should be used; abstinence is acceptable 5. Have a pap smear test documenting, ASCUS, ASC-H, LSIL or HSIL within 3 months of screening 6. 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 7. Have satisfactory colposcopy, i.e. the entire aceto-white or disease area as well as the entire squamocolumnar junction visualized by colposcopy 8. 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 section 3.1 9. Have no clinically significant out of range hematological, renal, or hepatic laboratory tests. Specifically, patients should have white blood cell count >3x1'000'000'000/L, hemoglobin>10g/dL, platelet count >150'000/µL; ALT=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Have colposcopically visible CIN2/3 disease extending over more than 2 quadrants 2. Have had any previous excisional or ablative surgical treatment for CIN 3. Have vulvar (VIN) or vaginal (VAIN) intraepithelial neoplasia 4. Have atypical endometrial or glandular cells or evidence of carcinoma on biopsy 5. 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 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 6. Have previously received a prophylactic HPV vaccine 7. Have a serious, concomitant disorder, including active systemic infection requiring treatment 8. 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 9. Have a proven or suspected immunosuppressive disorder or autoimmune disease 10. Have any significant cardiac, hepatic or renal disease 11. Are breast-feeding 12.Have a known allergy to eggs 13. Have previous (within 4 weeks prior to Day 1) concomitant long term treatment with systemic steroids, immunosuppressive/immunomodulating drugs (e.g. cyclosporine, corticosteroids). Steroid nasal sprays, inhaled steroids for asthma and/or topical steroids are permissible 14. Have received any vaccination within 30 days of study treatment 15. Have active significant viral infections including HIV, HCV, HBV, CMV, and EBV within 30 days of receiving study treatment. Mild viral infections such as HSV-1 or common cold are not excluded 16. Have participated in another experimental protocol/use of investigational drug during the prior 6 months 17. Are unable to comply with the protocol requirements 18. Have any condition that, in the judgment of the investigator, might prevent safe participation in the study or interfere with study objectives.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Interim analysis: - To assess the efficacy, in the IA population, of RO5217790 compared to placebo in achieving histologic resolution at Month 6 (determined by evaluation of tissue derived from surgical excision of the entire lesion area). Full analysis: - To assess the efficacy of RO5217790 compared to placebo in achieving histologic resolution at Month 6 (determined by evaluation of tissue derived from surgical excision of the entire lesion area) in patients with CIN2/3 associated with HPV16 single infection i.e. stratum 1 (see Section 3.1 of protocol);Secondary Objective: - Viral clearance by DNA and mRNA at Month 3 and Month 6; - Cellular and humoral immunological response following treatment; - Safety and tolerability. Exploratory Objectives: - To assess the change in QoL parameters using the short form 36 questionnaire; - To assess pain levels following injection and conization using a 100mm visual analog scale (VAS); - The RCR will be used to study the association of biomarkers with efficacy and/or adverse reactions related to RO5217790; and/or develop biomarker or diagnostic assays; establish the performance characteristics of these assays.;Primary end point(s): The dichotomous primary efficacy endpoint is defined for a patient as the occurrence or non-occurrence of an histological response at the six month evaluation as defined by a diagnosis of no CIN following conization in patients with HPV 16 single infection. Diagnostic category (i) to (iv) equivalent to no CIN (see appendix 5 for category definitions). For the full analysis, the primary end-point will be applied sequentially to patients from stratum 1 only, then the ITT population. | — |
Countries
Belgium, Finland, Germany, Spain
Outcome results
None listed