Ignite Creation Date:
2024-05-06 @ 1:53 AM
Last Modification Date:
2024-10-26 @ 11:11 AM
Study NCT ID:
NCT01923116
Status:
COMPLETED
Last Update Posted:
2018-03-15
First Post:
2013-08-06
Brief Title:
Therapeutic HPV-16 Vaccination for the Treatment of Anal Dysplasia
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Organization:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Study Overview
Official Title:
Therapeutic Vaccination Against Human Papillomavirus Type 16 for the Treatment of Anal Intraepithelial Neoplasia in HIV Men
Status:
COMPLETED
Status Verified Date:
2018-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
VACCAIN-T
Brief Summary:
The objective of the study is to assess in a phase 12 study the safety and efficacy of this synthetic vaccine SLP-HPV-01 in HIV men with CD4 counts 350 x 10E6l and HPV16-induced intra-anal high-grade AIN grade 2-3 that failed on or recurred after previous treatment
Detailed Description:
Rationale Since the introduction of combination antiretroviral therapy cART human immunodeficiency virus HIV-related morbidity and mortality have considerably decreased However as a result of the significantly prolonged life span of HIV-positive patients new causes of morbidity and mortality have become evident In particular anal cancer incidence has increased dramatically in HIV-positive men Like cervical cancer anal cancer is causally linked to infections with high-risk papillomaviruses HPV and is preceded by cancer precursor lesions anal intraepithelial neoplasia AIN Over 90 of HIV-positive MSM have persisting anal HPV infection in 88 of patients high-risk HPV is present and high-grade disease AIN 2 or 3 HG AIN is present in 25-52 of all HIV MSM The majority of HG AIN is caused by HPV type 16 As in cervical intraepithelial neoplasia early diagnosis and treatment of AIN have been advocated to prevent malignancy
Several treatment options exist for AIN but success rates are disappointingly low An alternative strategy might be therapeutic HPV vaccination In women with vulvar intraepithelial neoplasia VIN a condition with a comparable pathogenesis therapeutic vaccination with a synthetic long-peptide vaccine SLP-HPV-01 consisting of a mix of long peptides from the HPV-16 viral oncoproteins E6 and E7 was well tolerated and proved to be effective in a high percentage of women with a durable response and induction of HPV-16-specific immunity
Objective The objective of the current proposal is to assess in a phase 12 study the safety and efficacy of this synthetic vaccine SLP-HPV-01 in HIV men with CD4 counts 350 x 10E6l and intra-anal high-grade HPV16 positive AIN who failed on previous treatment
Study population HIV-positive MSM with a CD4 count 350 cellsul with HPV16-induced intra-anal high-grade AIN grade 2-3 that was resistant to or recurred after conventional cauterization or other forms of local treatment
During the past years the study group in the Academic Medical Center in Amsterdam has built a large cohort of well-characterized HIV-positive patients with histology-proven AIN Material has been stored of these patients and their lesions Those patients with AIN resistant to previous treatment will be identified The causative HPV type will be determined in stored biopsies of these patients using microdissection LCM and in-situ PCR Only patients with HPV-16-induced lesions the majority of patients will be eligible for the current study
Study design The first phase of the study is a dose-response study with four different dosage schedules 1510 51020 102040 and 40404040 μg of SLP-HPV-01 administered intradermally with a three-week interval each dosage schedule with or without the co-administration of pegylated interferon-α Pegintron 1 μgkg sc at the day of vaccine administration Each vaccination schedule is to be tested in 5 patients
The vaccination schedule that induces in HIV-positive MSM the best HPV16-specific response compared to that of the women with VIN in our previous study is considered the optimal schedule The size of this dose group will be increased to a total of 20 patients by treating an additional 15 patients
Intervention Patients will be vaccinated 3 or 4 times with a 3-week interval with the SLP-HPV-01 vaccine
High-resolution anoscopy HRA will be performed at inclusion and repeated at 3 612 and 18 months The transformation zone will be photographed at each visit Detailed photos plus biopsies of lesion sites will be obtained From venous blood samples PBMCs will be obtained before the first pre 3 weeks after the first vaccination post-1 3 weeks after the second vaccination post-2 3 weeks after the third vaccination post-3 and if applicable 3 weeks after the fourth vaccination post-4
Endpoints The primary clinical end points will be both toxicity safety and the regression of the lesions at 3 6 and 12 months as assessed by HRA with biopsies taken of lesion sites
Secondary endpoints are regression of lesions at 18 months and HPV16-specific immunity in blood will be measured ie ELISPOT IFNg for ex-vivo detection of antigen-specific responses and multiparametric intracellular cytokineextracellular activation marker staining to determine the type CD4 andor CD8 and function activation status andor cytokines of T-cells that respond
Several treatment options exist for AIN but success rates are disappointingly low An alternative strategy might be therapeutic HPV vaccination In women with vulvar intraepithelial neoplasia VIN a condition with a comparable pathogenesis therapeutic vaccination with a synthetic long-peptide vaccine SLP-HPV-01 consisting of a mix of long peptides from the HPV-16 viral oncoproteins E6 and E7 was well tolerated and proved to be effective in a high percentage of women with a durable response and induction of HPV-16-specific immunity
Objective The objective of the current proposal is to assess in a phase 12 study the safety and efficacy of this synthetic vaccine SLP-HPV-01 in HIV men with CD4 counts 350 x 10E6l and intra-anal high-grade HPV16 positive AIN who failed on previous treatment
Study population HIV-positive MSM with a CD4 count 350 cellsul with HPV16-induced intra-anal high-grade AIN grade 2-3 that was resistant to or recurred after conventional cauterization or other forms of local treatment
During the past years the study group in the Academic Medical Center in Amsterdam has built a large cohort of well-characterized HIV-positive patients with histology-proven AIN Material has been stored of these patients and their lesions Those patients with AIN resistant to previous treatment will be identified The causative HPV type will be determined in stored biopsies of these patients using microdissection LCM and in-situ PCR Only patients with HPV-16-induced lesions the majority of patients will be eligible for the current study
Study design The first phase of the study is a dose-response study with four different dosage schedules 1510 51020 102040 and 40404040 μg of SLP-HPV-01 administered intradermally with a three-week interval each dosage schedule with or without the co-administration of pegylated interferon-α Pegintron 1 μgkg sc at the day of vaccine administration Each vaccination schedule is to be tested in 5 patients
The vaccination schedule that induces in HIV-positive MSM the best HPV16-specific response compared to that of the women with VIN in our previous study is considered the optimal schedule The size of this dose group will be increased to a total of 20 patients by treating an additional 15 patients
Intervention Patients will be vaccinated 3 or 4 times with a 3-week interval with the SLP-HPV-01 vaccine
High-resolution anoscopy HRA will be performed at inclusion and repeated at 3 612 and 18 months The transformation zone will be photographed at each visit Detailed photos plus biopsies of lesion sites will be obtained From venous blood samples PBMCs will be obtained before the first pre 3 weeks after the first vaccination post-1 3 weeks after the second vaccination post-2 3 weeks after the third vaccination post-3 and if applicable 3 weeks after the fourth vaccination post-4
Endpoints The primary clinical end points will be both toxicity safety and the regression of the lesions at 3 6 and 12 months as assessed by HRA with biopsies taken of lesion sites
Secondary endpoints are regression of lesions at 18 months and HPV16-specific immunity in blood will be measured ie ELISPOT IFNg for ex-vivo detection of antigen-specific responses and multiparametric intracellular cytokineextracellular activation marker staining to determine the type CD4 andor CD8 and function activation status andor cytokines of T-cells that respond
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None