MSM with at least 6-month experience with PrEP (Pre-Exposure Prophylaxis)
Conditions
Interventions
Trade Name: Bexsero
Pharmaceutical Form: Suspension for injection in pre-filled syringe
Pharmaceutical Form: Tablet
Sponsors
INSERM ANRS
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: • MSM enrolled in the ANRS PREVENIR study • At least 6-month experience with PrEP (within the ANRS PREVENIR study or before starting the ANRS PREVENIR study) • No clinical manifestation of primary HIV infection and no symptom of bacterial STI (chlamydia, gonorrhea, M. genitalium or syphilis) • History of documented bacterial STI with at least one episode in the last 12 months • Participants who agree to sign the information and consent form specific to this study • Valid health insurance (“Aide Médicale d'Etat AME” is not health insurance) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 720 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Syphilis diagnosed prior to inclusion without serologic evidence of cure (cure is defined as decreased by at least 4-fold of the non-treponemal antibody titer [VDRL, RPR] relative to the titer at initiation of treatment of syphilis) • HIV infection. • Previous vaccination with Bexsero® • Systemic treatment with retinoids (Acnetrait®, Procuta®, Curacné®, Contracné®, ….). • Treatment with enzyme-inducing anticonvulsants (carbamazepine, phenobarbital, phenytoïne, ….) • Known or documented failure of the immune system, which would impair the immune response to the vaccine, such as subjects with inherited deficiency of complement, or immunosuppressive therapy • Known allergy to antibiotics of the tetracycline family • Known allergy to any component of the Bexsero® vaccine • Known allergy to any component of the doxycycline pill • Known allergy to latex (contained in the vaccine cap) • Thrombocytopenia or any other known coagulation disorder, which would be a contraindication to an intramuscular injection of Bexsero® vaccine • Documented esophageal lesion • Continuous treatment with doxycycline at D0DV/inclusion • Vitamin A treatment in case of intake of 10 000IU/d or more • Participation in another research including an exclusion period still in progress at the time of inclusion • Under guardianship or curatorship, or deprived of liberty by a judicial or administrative decision
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To demonstrate that post-exposure prophylaxis (PEP) with doxycycline reduces the occurrence of a first episode of syphilis or Chlamydia trachomatis - To demonstrate that the meningococcal B vaccine (Bexsero®) reduces the occurrence of first episode of Neisseria Gonorrheae ;Secondary Objective: - PEP-doxy : reduction in the occurrence of a 1st episode ofsyphilis (TP), chlamydia (CT, gonorrhea (NG) and Mycoplasma genitalium (MG), all cumulative episodes of TP, CT, NG and MG, a new episode of anal or urinary NG, a 1st episode of symptomatic anal and urinary NG or CT; impact on human microbiota; tolerance and compliance; antibiotic suceptibility; comparison of resistome and clonality of NG strains and negativity rate of STI diagnostic tests - Bexsero: reduction in the occurrence of cumulative episodes of NG, 1st episode of anal and urinary NG, 1st episode of symptomatic anal and urinary NG; serum bactericidal activity against meningococcus B and gonococci; tolerance - Prevalence and incidence of meningococcal carrying at the pharyngeal, anal and urinary levels and the impact of prophylaxis on it - Impact of each prophylaxis strategy on sexual behaviour and HIV incidence;Primary end point(s): The primary endpoint for intervention 1 (with or without doxycycline PEP) is the first episode of chlamydia or syphilis after the enrolment visit (J0DV) (chlamydia and syphilis diagnosed at the enrolment visit will not be included in the primary endpoint). The primary endpoint for intervention 2 (with or without Bexsero® vaccine) is the first episode of gonorrhea reported one month after the second vaccine injection, so starting at the month 3 visit (gonorrhea episodes diagnosed at the enrolment visit and before the month 3 visit will not be included in the primary endpoint). In these analyses, subject follow-up will be right-censored at the time of the first STI.;Timepoint(s) of evaluation of this end point: Intervention 1 : the date of the first episode of syphil | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The following secondary criteria will be compared between the treatment arms: 1- Occurrence of a first episode of each of the bacterial STIs as well as cumulative incidence of each bacterial STIs (syphilis, chlamydia; gonorrhoea and Mycoplasma genitalium) during the trial. In that case, the entire follow-up will be considered. 2- Occurrence of a new episode of anal or urinary gonorrhoea. 3- Occurrence of a first symptomatic episode of chlamydia infection or gonorrhea at urinary or anal sites. 4- Impact of doxycycline PEP on the human microbiota: detection from throat swab of carriage of Methicillin-Resistant Staphylococcus aureus (MRSA) and/or doxycycline resistant Staphylococcus aureus, fecal carriage of Extended Spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae, and composition of the intestinal microbiota). 5- Safety and adherence to PEP. 6- Antibiotic susceptibilities of all strains of NG, CT, MG to doxycycline, macrolides, fluoroquinolones and third generation cephalosporin for gonorrhea or TP PCR-positive samples with and without PEP. 7- Rate of cured STIs after treatment with or without PEP. 8- Composition of the resistome and clonality of Neisseria gonorrhoeae strains with or without doxycycline. 9- Serum bactericidal activity against meningococcal and gonococcal antigens over time in participants of Bexsero®’s arm. 10- Safety of Bexsero® vaccine. 11- Prevalence and incidence of meningococcal carriage in pharyngeal, anal and urine swabs. 12- Impact of PEP or Bexsero® vaccine on sexual behaviour (rates of condom use for receptive anal intercourse, number of sexual partners and number of sex acts over time). 13- Incidence of HIV infection with both prophylaxis strategies.;Timepoint(s) of evaluation of this end point: 1- 2- 3- M3DV, M6DV, M9DV, M12DV, M15DV, M18DV, M21DV and M24DV 4- At M12DV 5- At each visit : M3DV, M6DV, M9DV, M12DV, M15DV, M18DV, M21DV and M24DV 6- M12DV 7- 3 to 4 weeks after the completion of the specific | — |
Countries
France
Contacts
Public ContactDelphine LEBRASSEUR-LONGUET
INSERM ANRS
Outcome results
None listed