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Vaccination Against Human Papillomavirus (HPV) With the 9-valent Vaccine in HIV-positive Women (the Papillon Study) (Papillon)

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ClinicalTrials.gov Identifier: NCT03391921
Recruitment Status : Recruiting
First Posted : January 5, 2018
Last Update Posted : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Deborah Konopnicki, Centre Hospitalier Universitaire Saint Pierre

December 14, 2017
January 5, 2018
June 25, 2018
January 8, 2018
January 8, 2020   (Final data collection date for primary outcome measure)
Rate of seroconversion in HPV antibodies against HPV [ Time Frame: Month 7 ]
The rate of seroconversion of specific neutralizing antibodies against each HPV vaccine genotypes (6/11/16/18/31/33/45/52/58) one month after completion of a three doses schedule (0, 2 and 6 months) in women seronegative at baseline for these antibodies.
Same as current
Complete list of historical versions of study NCT03391921 on ClinicalTrials.gov Archive Site
  • Incidence of Treatment-Emergent Adverse Events (Safety and tolerability of the vaccines). [ Time Frame: day 2 to 7 after each vaccine administration ]
    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.
  • Impact of vaccine administration on T-lymphocyte CD4+ cell count and HIV viremia [ Time Frame: Month 7 ]
    The potential impact of vaccine administration on T-lymphocyte CD4+ cell count and HIV viremia 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.
  • Measure of the geometric mean titre of specific neutralizing antibodies against each HPV vaccine genotypes (6/11/16/18/31/33/45/52/58). [ Time Frame: Month 7 ]
    The measure of the geometric mean titre of specific neutralizing antibodies against each HPV vaccine genotypes (6/11/16/18/31/33/45/52/58) will be assessed before vaccination and 1 month after vaccination completion.
  • Cellular immune response [ Time Frame: Month 7 ]
    The cellular immune response will be evaluated in a subset of 40 patients (aged 18-40 years old) by measuring specific CD4+T cells expressing CD40, IL2, IFN-g or TNF-alpha against HPV 16/18/31/52 and 58. The analysis will be performed on a PMBC sample; a separate IC has to be signed for this sub-analysis
  • Incidence and prevalence rates of HPV infections [ Time Frame: Month 18 ]
    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.
  • The incidence and prevalence rates of abnormal cervical cytology [ Time Frame: Month 18 ]
    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.
  • Completion of vaccine schedule. [ Time Frame: Month 7 ]
    Rate of patients with completion of their vaccine schedule.
Same as current
Not Provided
Not Provided
 
Vaccination Against Human Papillomavirus (HPV) With the 9-valent Vaccine in HIV-positive Women (the Papillon Study)
Prospective Longitudinal Study on Immunogenicity, Induction of Cellular Immune Responses and Safety of Vaccination Against HPV With the 9-valent Vaccine in HIV-positive Women (The Papillon Study)
Phase IV prospective study measuring the immunogenicity (neutralizing antibody titles against each HPV vaccine genotype) of the 9-valent vaccine against HPV (Gardasil9®Merck, three doses at 0, 2 and 6 months) in HIV-positive women aged 15-40 years with fully suppressed HIV viremia on combined antiretroviral therapy. 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.

Number of patients:

Study: 200 patients Substudy on immune response analysis in a subset of patients: 40 patients and separated informed consent

Primary outcome:

The rate of seroconversion of specific neutralizing antibodies against each HPV vaccine genotypes (6/11/16/18/31/33/45/52/58) one month after completion of a three doses schedule (0, 2 and 6 months) in women seronegative at baseline for these antibodies. The measure will be performed on a 10 ml tube by chemiluminescence immunoassay (cLIA) technique in Merck laboratory .

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 and 1 month after vaccination completion.

  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. The rate of patients who could complete their full vaccine schedule will be calculated at month 7.

Number of visits:

5 mandatory visits at baseline, month 2, month 6, month 7 and month 18 plus 3 optional visits to be done in case of moderate or severe adverse reaction to vaccine administration

Interventional
Phase 4
Intervention Model: Single Group Assignment
Intervention Model Description:
All patients will receive the ninevalent vaccine against HPV (Garadsil9)
Masking: None (Open Label)
Primary Purpose: Prevention
  • HPV - Anogenital Human Papilloma Virus Infection
  • HIV Infections
Biological: Vaccine
All patients will receive the 9-valent vaccine against HPV (Gardasil9) 3 doses at 0,2 and 6 months intramuscularly
Vaccine
All patients will receive the 9-valent vaccine against HPV (Gardasil9) 3 doses at 0,2 and 6 months intramuscularly
Intervention: Biological: Vaccine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
200
Same as current
January 8, 2021
January 8, 2020   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV-positive woman
  • Age 15-40 years
  • Undetectable HIV viral load (HIVRNA <50 cp/ml) for at least 6 months (i,e: having at least two separate HIVRNA <50 cp/ml at 6 months intervals; the most recent HIVRNA <50 cp/ml may be performed with the baseline sample for the study).
  • No planned pregnancy foreseen for the next 7 months and use of contraception such as condom, hormonal contraception or intrauterine device
  • IC signed

Exclusion Criteria:

  • Previous hysterectomy or conisation
  • Previous or current biopsy-proven cervical, vulvar or vaginal HPV-associated lesion defined as ≥ cervical intraepithelial neoplasia grade 2(CIN2) ) , Vulvar intraepithelial neoplasia grade 2 (VIN2), vaginal intraepithelial neoplasia grade 2 (VaIN2 ) or invasive carcinoma
  • Previous vaccination against HPV (at least one dose)
  • Ongoing or planned pregnancy foreseen in the next 7 months
  • Other immunodeficiency conditions such as ongoing or previous (within 6 months) chemotherapy against cancer or chronic systemic corticosteroids treatment or immunosuppressive therapy after transplantation
  • Any condition contraindicating intramuscular injection such as warfarin therapy.
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: only female will be included
15 Years to 40 Years   (Child, Adult)
No
Contact: Deborah Konopnicki, MD, PhD +3225354130 deborah_konopnicki@stpierre-bru.be
Contact: Stephane De Wit, MD, PhD +3225354130 stephane_dewit@stpierre.be
Belgium
 
 
NCT03391921
CE/17-12-06
No
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Plan to Share IPD: Undecided
Deborah Konopnicki, Centre Hospitalier Universitaire Saint Pierre
Centre Hospitalier Universitaire Saint Pierre
Not Provided
Principal Investigator: Deborah Konopnicki, MD, PhD Centre Hospitalier Universitaire Saint Pierre
Centre Hospitalier Universitaire Saint Pierre
June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP