Therapeutic HPV-16 Vaccination for the Treatment of Anal Dysplasia (VACCAIN-T)
The objective of the study is to assess, in a phase 1/2 study, the safety and efficacy of this synthetic vaccine SLP-HPV-01® in HIV+ men with CD4 counts > 350 x 10E6/l and HPV16-induced intra-anal high-grade AIN (grade 2-3) that failed on, or recurred after previous treatment.
Anal Intraepithelial Neoplasia
Drug: HPV-16 vaccine
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Therapeutic Vaccination Against Human Papillomavirus Type 16 for the Treatment of Anal Intraepithelial Neoplasia in HIV+ Men|
- Safety/ toxicity of the HPV-16 vaccine in HIV+ MSM [ Time Frame: up to 18 months ] [ Designated as safety issue: Yes ]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. Adverse events are graded according to version 3.0 of the Common Terminology Criteria for Adverse Events (CTCAE), which grades events on a scale of 1 to 5, with higher grades indicating greater severity.
- Regression of intra-anal high grade AIN lesion [ Time Frame: Primary outcome: 3, 6, 12 months. Secondary: 18 months. ] [ Designated as safety issue: No ]High resolution anoscopy is performed to monitor the AIN lesions. Biopsies will be obtained of suspected lesions. Complete response is defined as histological resolution of AIN, partial response is defined as regression from high grade to low grade AIN. In case of persisting high grade AIN, a partial response is defined as a decrease in lesion size of 50% or more.
- HPV16-specific immunity in blood [ Time Frame: 3 weeks after the 1st, 2nd and 3rd vaccination ] [ Designated as safety issue: No ]
In order to assess the systemic changes in immunity, which are induced by vaccination we will examine venous blood samples by using peripheral blood lymphocytes that are tested by a set of complementary T-cell assays: i.e. proliferation (LST), cytokine production (IFNg, TNFa, IL-4, IL-5, IL-10, and IL-2) as well as by ELISPOT (IFNg) for ex-vivo detection of antigen-specific responses and by multiparametric intracellular cytokine/extracellular activation marker staining to determine the type (CD4+ and/or CD8+) and function of T-cells that respond.
A vaccine-induced response is defined as a 3-fold increase compared to the pre-vaccination result.
- Regression of peri-anal high grade AIN lesions [ Time Frame: 3, 6, 12 and 18 months ] [ Designated as safety issue: No ]High resolution anoscopy is performed to monitor the AIN lesions. Biopsies will be obtained of suspected lesions. Complete response is defined as histological resolution of AIN, partial response is defined as regression from high grade to low grade AIN. In case of persisting high grade AIN, a partial response is defined as a decrease in lesion size of 50% or more.
|Study Start Date:||August 2013|
|Estimated Study Completion Date:||October 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
|Experimental: HPV-16 vaccine||
Drug: HPV-16 vaccine
Vaccination with SLP-HPV-01® with or without interferon-a injections.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01923116
|Contact: Karien CM Gosens, MDfirstname.lastname@example.org|
|Contact: Jan M Prins, prof, MD, email@example.com|
|Academic Medical Center||Recruiting|
|Amsterdam, Noord-Holland, Netherlands, 1105 AZ|
|Contact: Karien CM Gosens, MD 0031205662575 firstname.lastname@example.org|
|Contact: Jan M Prins, professor 0031205664380 email@example.com|
|Principal Investigator: Jan M Prins, prof, MD|
|Principal Investigator:||Jan M Prins, prof, MD, infectiologist||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|
|Principal Investigator:||Henry JC de Vries, prof, MD, dermatologist||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|