Therapeutic Vaccination against HPV16 in HIV+ Men with anal dysplasia

Conditions: 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.
MedDRA version: 14.1Level: LLTClassification code 10059312Term: Anal dysplasiaSystem Organ Class: 100000004856
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2012-005466-34-NL

Lead Sponsor: Academic Medical Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Male

Target Recruitment: Not specified

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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

• Immunosuppressive medication or other diseases associated with immunodeficiency
• Life expectancy < 1 year
• History of anal carcinoma
• IFN-a criteria (see SmPC): severe cardiac, thyroid, hepatic or central nervous system disease, including severe depression in the past.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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. <br><br>;Secondary Objective: Not applicable;Primary end point(s): • Toxicity/ safety, <br>• Regression of the lesions at 3, 6 and 12 months, as assessed by HRA (high resolution anoscopy), with biopsies taken from the lesion site.<br>;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. <br><br>HRA will be performed at inclusion, and repeated at 3, 6 and 12 months.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Regression of lesions at 18 months, as assessed by HRA<br>• 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.<br>;Timepoint(s) of evaluation of this end point: HRA will be performed at 18 months.<br>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).