E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High grade cervical intraepithelial neoplasia grade 2 or 3 associated with High Risk HPV infection |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049701 |
E.1.2 | Term | Cervical intraepithelial neoplasia II |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049702 |
E.1.2 | Term | Cervical intraepithelial neoplasia III |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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) |
|
E.2.2 | Secondary objectives of the trial |
- 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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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<2.0xULN, AST <2xULN (upper limit of normal) and serum creatinine <2mg/dL
|
|
E.4 | Principal 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.
|
|
E.5 End points |
E.5.1 | 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.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker discovery, Immunology, Quality of life |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The definition of end of trial for this study is Last Patient Last Visit (LPLV) for the follow-up period, i.e. the last visit is the month 30 visit.
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |