Ignite Creation Date:
2024-05-06 @ 2:37 AM
Last Modification Date:
2024-10-26 @ 11:21 AM
Study NCT ID:
NCT02087384
Status:
COMPLETED
Last Update Posted:
2021-03-05
First Post:
2014-03-07
Brief Title:
HPV Human Papilloma Virus Vaccination After Treatment of Anal Intraepithelial Neoplasia AIN
Sponsor:
Prof Jan Prins
Organization:
Academisch Medisch Centrum - Universiteit van Amsterdam AMC-UvA
Study Overview
Official Title:
Quadrivalent HPV Vaccination After Effective Treatment of Anal Intraepithelial Neoplasia in HIV Men
Status:
COMPLETED
Status Verified Date:
2021-03
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-P
Brief Summary:
This study evaluates vaccination with the quadrivalent HPV vaccine Gardasil versus placebo vaccination on prevention of high grade AIN recurrence in HIV-positive MSM men who have sex with men who were successfully treated for high grade AIN
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 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 and is preceded by precursor lesions anal intraepithelial neoplasia AIN Over 90 of HIV-positive MSM men who have sex with men have persisting anal HPV human papilloma virus infection and high-grade HG AIN is present in 30 of all HIV MSM
As in cervical intraepithelial neoplasia early diagnosis and treatment of AIN have been advocated to prevent malignancy Electrocoagulation cauterization is standard of care for intra-anal AIN but after treatment recurrence of lesions occurs in approx 50 of cases This is a major problem in an effective screening program for AIN
In a nonconcurrent non-blinded cohort study qHPV quadrivalent human papilloma virus vaccination significantly HR 050 reduced HG AIN recurrence among MSM successfully treated for AIN This is in accordance with findings in women treated for cervical intraepithelial neoplasia Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease including high grade disease
Therefore a strategy that is worth investigating is vaccination with the qHPV vaccine to prevent recurrences in HIV MSM who were successfully treated for HG AIN
Objective The primary objective of the current study is to assess the efficacy of qHPV vaccination in preventing recurrence of high-grade AIN in HIV MSM with CD4 counts 350 x 10E6l who were successfully treated for high-grade intra-anal AIN in the past year
Study population HIV-positive MSM with a CD4 count 350 cellsul and intra-anal high-grade AIN grade 2-3 that was successfully treated in the past year with conventional cauterization cryotherapy or other forms of local treatment
Study design A multicenter randomised double-blind clinical trial in four hospitals in the Netherlands
Intervention Patients are randomised for vaccination with the quadrivalent HPV vaccine Gardasil or vaccination with a matching placebo at months 0 2 and 6
Randomisation will be stratified for complete response versus partial response from HG AIN to low-grade LG AIN of the initial HG AIN lesion for treatment less than 6 months ago versus treatment 6 months and longer ago and for AMC versus other hospitals
Main study parametersendpoints Screening for AIN will be performed by high-resolution anoscopy HRA at inclusion first vaccination and at last vaccination 6 months and repeated at 6 and 12 months after the last vaccination Safety Monitoring for adverse events and injection-site reactions will be performed one week after each vaccination and thereafter every 6 months for a total of 12 months of follow-up
Primary end point will be the cumulative recurrence of HG AIN at 12 months after the last vaccination as assessed by HRA High-Resolution Anoscopy with biopsies taken of suspect lesions
Secondary outcome measures are toxicity safety recurrence of HG AIN at last vaccination and 6 months afterwards cumulative occurrence of LG AIN at 12 months after the last vaccination cumulative occurrence of anogenital warts at 12 months after the last vaccination causative HPV type in recurrent AIN lesions as assessed by LCM Laser Capture Microdissection PCR polymerase chain reaction and HPV type-specific antibody response
The total sample size is estimated to be 125 patients based on an expected recurrence rate of 50 within 12 months Statistical analysis will be based on the intention-to-treat principle Both primary and secondary endpoints will be analyzed by descriptive statistics and the chi-square test with a 005 two-sided significance level
Nature and extent of the burden and risks associated with participation benefit and group relatedness
HIV MSM who were successfully treated for HG AIN are still at a 50 risk for recurrences with additional treatment sessions needed and an ongoing risk for malignant degeneration of lesions
Costs of 3 vaccinations are approx 400 but if vaccination reduces recurrence rates by 50 this will be a highly cost-effective intervention very likely to be introduced into regular care
For the study patients will be vaccinated 3 times with the quadrivalent vaccine Gardasil or placebo and will undergo two extra HRAs Clinical trial data show that the most common adverse events of Gardasil were mild or moderate so few risks are associated with study participation
As in cervical intraepithelial neoplasia early diagnosis and treatment of AIN have been advocated to prevent malignancy Electrocoagulation cauterization is standard of care for intra-anal AIN but after treatment recurrence of lesions occurs in approx 50 of cases This is a major problem in an effective screening program for AIN
In a nonconcurrent non-blinded cohort study qHPV quadrivalent human papilloma virus vaccination significantly HR 050 reduced HG AIN recurrence among MSM successfully treated for AIN This is in accordance with findings in women treated for cervical intraepithelial neoplasia Previous vaccination with quadrivalent HPV vaccine among women who had surgical treatment for HPV related disease significantly reduced the incidence of subsequent HPV related disease including high grade disease
Therefore a strategy that is worth investigating is vaccination with the qHPV vaccine to prevent recurrences in HIV MSM who were successfully treated for HG AIN
Objective The primary objective of the current study is to assess the efficacy of qHPV vaccination in preventing recurrence of high-grade AIN in HIV MSM with CD4 counts 350 x 10E6l who were successfully treated for high-grade intra-anal AIN in the past year
Study population HIV-positive MSM with a CD4 count 350 cellsul and intra-anal high-grade AIN grade 2-3 that was successfully treated in the past year with conventional cauterization cryotherapy or other forms of local treatment
Study design A multicenter randomised double-blind clinical trial in four hospitals in the Netherlands
Intervention Patients are randomised for vaccination with the quadrivalent HPV vaccine Gardasil or vaccination with a matching placebo at months 0 2 and 6
Randomisation will be stratified for complete response versus partial response from HG AIN to low-grade LG AIN of the initial HG AIN lesion for treatment less than 6 months ago versus treatment 6 months and longer ago and for AMC versus other hospitals
Main study parametersendpoints Screening for AIN will be performed by high-resolution anoscopy HRA at inclusion first vaccination and at last vaccination 6 months and repeated at 6 and 12 months after the last vaccination Safety Monitoring for adverse events and injection-site reactions will be performed one week after each vaccination and thereafter every 6 months for a total of 12 months of follow-up
Primary end point will be the cumulative recurrence of HG AIN at 12 months after the last vaccination as assessed by HRA High-Resolution Anoscopy with biopsies taken of suspect lesions
Secondary outcome measures are toxicity safety recurrence of HG AIN at last vaccination and 6 months afterwards cumulative occurrence of LG AIN at 12 months after the last vaccination cumulative occurrence of anogenital warts at 12 months after the last vaccination causative HPV type in recurrent AIN lesions as assessed by LCM Laser Capture Microdissection PCR polymerase chain reaction and HPV type-specific antibody response
The total sample size is estimated to be 125 patients based on an expected recurrence rate of 50 within 12 months Statistical analysis will be based on the intention-to-treat principle Both primary and secondary endpoints will be analyzed by descriptive statistics and the chi-square test with a 005 two-sided significance level
Nature and extent of the burden and risks associated with participation benefit and group relatedness
HIV MSM who were successfully treated for HG AIN are still at a 50 risk for recurrences with additional treatment sessions needed and an ongoing risk for malignant degeneration of lesions
Costs of 3 vaccinations are approx 400 but if vaccination reduces recurrence rates by 50 this will be a highly cost-effective intervention very likely to be introduced into regular care
For the study patients will be vaccinated 3 times with the quadrivalent vaccine Gardasil or placebo and will undergo two extra HRAs Clinical trial data show that the most common adverse events of Gardasil were mild or moderate so few risks are associated with study participation
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