Therapeutic HPV-16 Vaccination for the Treatment of Anal Dysplasia (VACCAIN-T)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Collaborators:
Leids Universitair Medisch Centrum
ISA Therapeutics B.V.
Information provided by (Responsible Party):
Prof. Jan Prins, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01923116
First received: August 6, 2013
Last updated: June 26, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Anal Intraepithelial Neoplasia
HIV
Drug: HPV-16 vaccine
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Estimated Enrollment: 45
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)
Arms Assigned Interventions
Experimental: HPV-16 vaccine Drug: HPV-16 vaccine
Vaccination with SLP-HPV-01® with or without interferon-a injections.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Age ≥ 18 years
  • HIV+, CD4 count > 350/ul (maximum 3 months before screening visit)
  • Biopsy-proven intra-anal high-grade AIN caused by HPV16, resistant to, or recurring after previous treatment with cauterization (or other local treatment), 5FU or imiquimod. A patient is considered resistant to cauterization if after 2 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. This means: Leukocytes >3 x 109/L, lymfocytes >1 x 109/L, trombocytes >100 x 109/L and hematocrit >30%.

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.
  • Previous HPV vaccination
  • Currently treated with IFN-α against hepatitis C
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01923116

Contacts
Contact: Karien CM Gosens, MD 0031205662575 k.c.gosens@amc.nl
Contact: Jan M Prins, prof, MD, infectiologist 0031205664380 j.m.prins@amc.nl

Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Noord-Holland, Netherlands, 1105 AZ
Contact: Karien CM Gosens, MD    0031205662575    k.c.gosens@amc.nl   
Contact: Jan M Prins, professor    0031205664380    j.m.prins@amc.nl   
Principal Investigator: Jan M Prins, prof, MD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Leids Universitair Medisch Centrum
ISA Therapeutics B.V.
Investigators
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)
  More Information

No publications provided

Responsible Party: Prof. Jan Prins, Prof. dr. J.M. Prins, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01923116     History of Changes
Other Study ID Numbers: NL42802.000.12
Study First Received: August 6, 2013
Last Updated: June 26, 2015
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Anal intraepithelial neoplasia
HIV
HPV
Vaccination
Treatment

Additional relevant MeSH terms:
Carcinoma in Situ
Neoplasms
Carcinoma
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on June 30, 2015