E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HPV16-induced intra-anal high-grade AIN (grade 2-3) in HIV+ men, that was resistant to, or recurred after conventional cauterization 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 |
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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 |
The objective of the current proposal is to assess, in a phase 1/2 study, the safety and efficacy of a synthetic vaccine SLP-HPV-01® in HIV+ men with CD4 counts > 350 x 10E6/l and intra-anal high-grade, HPV16 positive AIN, who failed on previous treatment.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent
• HIV+, CD4 count > 350/ul,
• Biopsy-proven intra-anal high-grade AIN caused by HPV16, resistant to, or recurring after previous treatment with cauterization, 5FU or imiquimod. A patient is considered resistant to cauterization if after 3 cauterization sessions still lesions are found. A patient is considered resistant to 5FU or imiquimod if after 4 months of weekly (multiple day) application still lesions are found.
• 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 as described previously
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E.4 | Principal exclusion criteria |
• Immunosuppressive medication or other diseases associated with immunodeficiency
• Life expectancy < 1 year
• History of anal carcinoma
• IFN-α criteria (see SmPC): severe cardiac, thyroid, hepatic or central nervous system disease, including severe depression in the past.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Toxicity/ safety,
• Regression of the lesions at 3, 6 and 12 months, as assessed by HRA (high resolution anoscopy), with biopsies taken from the lesion site.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monitoring for spontaneous adverse events and injection-site reactions will be done weekly for three weeks after each vaccination, clinical assessments and laboratory tests (routine hematology and chemistry) will be performed before the second and third vaccination and thereafter every 3 months for a total of 18 months of follow-up.
HRA will be performed at inclusion, and repeated at 3, 6 and 12 months. |
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E.5.2 | Secondary end point(s) |
• Regression of lesions at 18 months, as assessed by HRA
• HPV16-specific immunity in blood will be measured: ELISPOT (IFNg) for ex-vivo detection of antigen-specific responses and multiparametric intracellular cytokine/extracellular activation marker staining to determine the type (CD4+ and/or CD8+) and function (activation status and/or cytokines) of T-cells that respond.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
HRA will be performed at 18 months.
For the evaluation of the HPV-16 specific immunity, venous blood samples will be drawn before the first (pre), 3 weeks after the first (post-1), 3 weeks after the second vaccination (post-2) as well as 3 weeks after 3th vaccination (post-3). |
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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 | 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 | Yes |
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) | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |