E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune responses to administration of 9valent vaccine against HPV in HIV-positive women |
|
E.1.1.1 | Medical condition in easily understood language |
Immune responses against HPV after administration of 9valent vaccine in HIV-positive women |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020180 |
E.1.2 | Term | HIV positive |
E.1.2 | System Organ Class | 100000004848 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the immunogenicity (both humoral and cellular responses) and the safety of the 9valent vaccine against HPV (Gardasil9®Merck) in HIV-positive women aged 15-40 years with fully suppressed HIV viremia on combined antiretroviral therapy after randomization between two different doses schedules: in the first schedule 5arm A), women will receive 2 doses at time 0 and 6 months and a third facultative dose between 18-48 months if their antibody levels at month 7 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 2 doses of vaccination (month 7) defined as at least 80% of the patients receiving 2 doses have a seroconversion rate. |
|
E.2.2 | Secondary objectives of the trial |
• Completion of vaccine schedule. • Safety and clinical tolerance of the vaccine administration. • Impact on T-lymphocytes CD4+ counts and HIV viremia at month 7. • Measure of neutralizing antibodies title against each HPV vaccine genotypes • The cellular immune response against HPV 16/18/31/52/58 will be assessed in a subgroup of patients (n=40: 20 from ARM A and 20 from ARM B) on PBMC samples tested. For this analysis, a separated IC should be first signed by the patient. • Incidence and prevalence of HPV infections performed by PCR on cervical swab at baseline and 12 months after the end of vaccination. • Incidence and prevalence of abnormal cervical cytology performed by cytology on cervical swab at baseline and 12 months after the end of vaccination. • the proportion of participants in ARM A (2 doses schedule) needing a third dose booster. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The cellular immune responses against HPV 16/18/31/52/58 will be assessed in a subgroup of patients (n=40: 20 from ARM A and 20 from ARM B) on PBMC samples tested. For this analysis, a separated IC should be first signed by the patient. |
|
E.3 | Principal inclusion criteria |
• HIV-positive woman • Age 15-40 years • Undetectable HIV viral load (HIVRNA <400 cp/ml) for at least 6 months (i,e: having at least two separate HIVRNA <400 cp/ml at 6 months intervals; the most recent HIVRNA <400 cp/ml may be the screening CV 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
|
|
E.4 | Principal exclusion criteria |
• Previous hysterectomy or conisation • Previous or current biopsy-proven cervical, vulvar or vaginal HPV-associated high grade lesions defined as ≥ CIN2, VIN2, 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.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The rate of seroconversion in 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 and at month 7 (i.e. one month after last vaccine dose).Non inferiority of ARM A compared to ARM B will be reached if for each HPV genotype contained in the vaccine, at least 80% of the patients have a seroconversion rate. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Completion of vaccine schedule. • Safety and clinical tolerance of the vaccine administration. • Impact on T-lymphocytes CD4+ counts and HIV viremia at month 7. • Measure of neutralizing antibodies title against each HPV vaccine types • The cellular immune response against HPV 16/18/31/52/58 will be assessed in a subgroup of patients (n=40: 20 from ARM A and 20 from ARM B) on PBMC samples tested. For this analysis, a separated IC should be first signed by the patient. • Incidence and prevalence of HPV infections performed by PCR on cervical swab at baseline and 12 months after the end of vaccination. • Incidence and prevalence of abnormal cervical cytology performed by cytology on cervical swab at baseline and 12 months after the end of vaccination. • the proportion of participants in ARM A (2 doses schedule) needing a third dose booster. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Month 7: rate of antibodies seroconversion, measure of GMT antibodies, completion of vaccine schedule, safety and tolerability of vaccine, impact on CD4 and HIVRNA and the proportion of participants in ARM A (2 doses schedule) needing a third dose booster.
Month 18: Incidence and prevalence of HPV infections and of abnormal cervical cytology, |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
the comparator is the same vaccine Gardasil9 but given according to another schedule |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |