Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03391921 |
| Other study ID # |
CE/17-12-06 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 8, 2018 |
| Est. completion date |
May 2, 2026 |
Study information
| Verified date |
February 2024 |
| Source |
Centre Hospitalier Universitaire Saint Pierre |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Phase IV prospective study measuring the immunogenicity (neutralizing antibody titles against
each HPV vaccine genotype) of the 9-valent vaccine against HPV (Gardasil9®Merck) in
HIV-positive women aged 15-40 years with fully suppressed HIV viremia on combined
antiretroviral therapy.
After a first open phase evaluating tolerability of Gardasil9 (from June 2018 to December
2018), an amendment was introduced to randomize women between two different doses schedules:
in the first schedule (ARM A), women will receive 2 doses at time 0 and 6 months and a third
dose between 18-48 months if their antibody levels are insufficient; the second schedule (ARM
B) will be 3 doses at 0, 2 and 6 months. Primary outcome is the non-inferiority of the rate
of seroconversion against each HPV vaccine genotypes in women seronegative at baseline after
either 2 or 3 doses of vaccination (month 7). Secondary outcomes are rate of seroconversion
after 3 doses if they have received a third dose, completion of vaccine schedule, vaccine
safety, antibody titles, and induction of cellular immunity against HPV contained in the
vaccine, incidence of cervical HPV infection and incidence of abnormal cytology after
vaccination. The safety of the vaccination (local or systemic reaction and impact on HIV
viral control and immunodeficiency level) will be assessed. The cellular immune response will
be assessed in a subgroup of patients.
Description:
Number of patients:
Study: 200 patients: 50 in the first open label phase (june 2018 to dec 2018), then n=150 in
the randomized phase starting in January 2019 Substudy on immune response analysis in a
subset of patients: 40 patients and separated informed consent
Primary outcome:
Rate of seroconversion of neutralizing antibodies against each HPV vaccine genotypes namely
6/11/16/18/31/33/45/52/58 among women seronegative at baseline for HPV vaccine genotypes, by
measuring neutralizing antibody against the 9 vaccine genotypes of HPV at baseline, month 7.
The measure will be performed on a 10 ml tube by chemiluminescence immunoassay (cLIA)
technique in Merck laboratory .Comparison of that rate at month 7 (non inferiority defined as
at least 80% of seroconversion in ARM A).
Secondary outcomes:
1. Incidence of Treatment-Emergent Adverse Events (Safety and tolerability of the
vaccines).
It will be evaluated by a specific questionnaire on a phone call made by the research
team to the participant and scheduled at least 48 hours and maximum 7 days after each
vaccine dose; the questionnaire will evaluate whether there is any complain regarding
local reaction (pain, redness, swelling, pruritus), systemic reaction (fever, malaise
and fatigue) or other side effect. In case of any usual complain > mild stage, or the
presence of an unusual complain, the patient will be assessed by a visit and physical
examination performed by the research team. The questionnaire has been elaborated
according to the published data on safety evaluation of the 9-valent vaccine.
2. The potential impact of vaccine administration on T-lymphocyte-CD4+ cell count and HIV
viremia It will be assessed by measuring CD4 cell count and HIV viremia at baseline (any
measure within 6 months before screening can be taken into account) and month 7. Any
detectable HIVRNA >50 cp/ml will be reassessed on a second samples taken 2-4 weeks
later. Any significant decrease in T-lymphocyte-CD4+ cell count (defined as a decrease
by more of 5% in the percentage or >100 cells/µl) will be reassessed on a second sample
taken 2-4 weeks later.
3. Measure of the geometric mean titre of specific neutralizing antibodies against each HPV
vaccine genotypes (6/11/16/18/31/33/45/52/58).
It will be assessed before vaccination, 1 month after vaccination completion (month 7)
and 12 months after vaccination completion (month 18).
4. The cellular immune response The cellular immune response ill be evaluated in a subset
of 40 patients (aged 18-40 years old) by measuring specific T-lymphocytes-CD4+ cells
expressing CD40-receptor, interleukin-2 (IL2), interferon gamma (IFN-g) or Tumor
necrosis factor (TNF-alpha ) against HPV 16/18/31/52 and 58. The analysis will be
performed on a peripheral blood mononuclear cell (PBMC) sample of 30 to 50 ml taken at
baseline and at month 7; a separate informed consent (IC) has to be signed for this
sub-analysis.
5. The incidence and prevalence rates of cervical HPV infections:
Detection of HPV will be performed by molecular technique by the national reference
center for HPV (AML, Antwerpen), performed on cervical swab taken by the gynecologist at
baseline and month 18. The baseline gynecological sample might have been taken up to 6
months before the vaccination. These swabs will be sampled in all participants with
previous vaginal sexually activity. In case of no previous vaginal sexual intercourse,
the samples will not be taken.
6. The incidence and prevalence rates of abnormal cervical cytology:
Cervical cytology will be performed by by the national reference center for HPV (AML,
Antwerpen) on cervical swab taken by the gynecologist at baseline and month 18. The
baseline gynecological sample might have been taken up to 6 months before the
vaccination. These swabs will be sampled in all participants with previous vaginal
sexually activity. In case of no previous vaginal sexual intercourse, the samples will
not be taken.
7. Completion of vaccine schedule. Comparison of the proportion of women achieving full
course of vaccine administration in each arm, namely for ARM A receiving 2 doses and for
ARM B receiving 3 doses.
8. Proportion of patients needing a booster dose (i.e..a third dose) in ARM A If after 2
doses of vaccine (ARM A), the month 7 antibodies analysis shows absence of
seroconversion against one of the HPV genotypes contained in the vaccine, the
participant will receive a third booster dose
Number of visits:
4 to 5 mandatory visits at baseline, month 2 (not if ARM A), month 6, month 7 and month 18
plus 2 to 3 optional visits to be done in case of moderate or severe adverse reaction to
vaccine administration
