E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Intra-anal high-grade anal intraepithelial neoplasia (AIN) (grade 2-3) in HIV+ men that was successfully treated in the past year with conventional cauterization, cryotherapy, or other forms of local treatment.
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E.1.1.1 | Medical condition in easily understood language |
Anal dysplasia in HIV-positive men that was successfully treated with local therapy. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059312 |
E.1.2 | Term | Anal dysplasia |
E.1.2 | System Organ Class | 100000004856 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of qHPV vaccination in preventing recurrence of high-grade AIN in HIV+ MSM with CD4 counts >350 x 10E6/l who were successfully treated in the past year for high-grade intra-anal AIN. |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety of vaccination in this patient group
- To assess the efficacy of qHPV vaccination in preventing occurrence of low-grade AIN
- To assess the occurrence of anogenital warts
- To assess the causative HPV genotype of recurrent LG and HG AIN lesions
- To assess the HPV type-specific antibody response after vaccination, and relate this to the efficacy parameters
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent
• HIV+ MSM, CD4 count > 350/ul.
• Biopsy-proven intra-anal high-grade AIN successfully treated in the past year with cauterization, cryotherapy, Efudix, imiquimod or another form of local treatment. Lesions with regression from HG to Low grade (LG) AIN will also be eligible.
• Lesion (still) in remission at the moment of first vaccination (a maximum interval of 6 weeks between last HRA and first vaccination is allowed).
• Good performance status (a Karnofsky performance score of >= 60 [on a scale of 0 to 100, with higher scores indicating better performance status])
• Normal pretreatment laboratory blood values
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E.4 | Principal exclusion criteria |
• Immunosuppressive medication or other diseases associated with immunodeficiency
• Life expectancy less than one year
• Previous vaccination with the bivalent or quadrivalent HPV vaccine
• History of anal cancer |
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E.5 End points |
E.5.1 | Primary end point(s) |
Cumulative recurrence of intra-anal or peri-anal HG AIN at 12 months after the last vaccination, as assessed by HRA, with biopsies taken of suspect lesions. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 months after the last vaccination |
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E.5.2 | Secondary end point(s) |
• Toxicity/ safety.
• Recurrence of intra-anal or peri-anal HG AIN at the moment of last vaccination and 6 months afterwards.
• Cumulative occurrence of intra-anal or peri-anal LG AIN at 12 months after the last vaccination
The patients with LG AIN at inclusion are excluded from this analysis.
• Cumulative occurrence of anogenital warts at 12 months after the last vaccination, evaluated by physical examination and history taking.
• Causative HPV type in recurrent AIN lesions, as assessed by LCM/ PCR.
• HPV type-specific antibody response.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 and 12 months after the last vaccination |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
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Last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |