Clinical trial NCT04597424: Combined Prevention of Sexually Transmitted Infections (STIs) in Men Who Have Sex With Men and Using Oral Tenofovir Disoproxil Fumarate/ Emtricitabine (TDF/FTC) for HIV Pre-Exposure Prophylaxis (PrEP)
Official title: Combined Prevention of Sexually Transmitted Infections (STIs) in Men Who Have Sex With Men and Using Oral Tenofovir Disoproxil Fumarate/ Emtricitabine (TDF/FTC) for HIV Pre-Exposure Prophylaxis (PrEP)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Unsafe Sex
Risk-Taking
Keywords: STI infection
PREVENTION
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2020-10-22
Enrollment: 556
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1 : doxycycline and Bexsero vaccine Arm 2 : doxycycline and no vaccine Arm 3 : No doxycycline and Bexsero vaccine Arm 3 : No doxycycline and No Bexsero vaccine
Primary purpose: TREATMENT

Brief summary: The study ANRS 174 Doxyvac is a clinical trial that will use Combined Prevention of Sexually Transmitted Infections (STIs) in Men Who Have Sex with Men and using oral TDF/FTC for HIV Pre-Exposure Prophylaxis (PrEP) and vaccination with Bexsero.

Detailed description: This is a randomized study with a factorial design for the 2 biomedical interventions (interventions 1 and 2).

Subjects will be randomized and assigned to two different interventions:

* Intervention 1: PEP with doxycycline or no PEP. Subjects will be randomized 2/1 to receive doxycycline PEP or no PEP
* Intervention 2: Meningococcal B vaccine (Bexsero®) or no vaccine Subjects will be randomized 1/1 to received 2 doses of Bexsero® vaccine (at the first visit and two months later) or no vaccine

Participants will be randomized in one of the following arms:

* Arm 1: doxycycline and Bexsero® vaccine (240 participants)
* Arm 2: doxycycline and no Bexsero® vaccine (240 participants)
* Arm 3: no doxycycline and Bexsero® vaccine (120 participants)
* Arm 4: no doxycycline and no Bexsero® vaccine (120 participants)

Randomization will be stratified by whether or not the participant enters in the ancillary study "intestinal microbiota".

Eligibility criteria: Inclusion Criteria:

* Mens who have sex with mens (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 (State medical aid (AME) is not health insurance).

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 \[Venereal Disease Research Laboratory (VDRL), Rapid Plasma Reagin (RPR)\] relative to the titer at initiation of treatment of syphilis).
* HIV infection.
* Previous vaccination with Bexsero® or any other meningococcal B vaccine.
* Vaccination during the 4 weeks (28 days) preceding the first vaccination of the study.
* Previous vaccination with an experimental vaccine in the previous 5 years.
* Systemic treatment with retinoids : isotretinoin (Acnetrait®, Procuta®, Curacné®, Contracné®, ...).
* Treatment with enzyme-inducing anticonvulsants (carbamazepine, phenobarbital, phenytoin, ....).
* Participant who has received immunoglobulins, a transfusion of blood or blood derivatives in the last 3 months.
* Known or suspected congenital or acquired immunodeficiency; immunosuppressive treatment in the last 6 months, such as cancer chemotherapy or radiotherapy; long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks in the last 3 months)
* 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 oesophageal lesion
* Acute respiratory infection or severe acute febrile illness or systemic reaction that may present a significant risk if vaccinated in the month prior to inclusion.
* Any condition (clinical) that, in the investigator's opinion, would contraindicate intramuscular vaccination and blood sampling.
* Oral Anticoagulant treatment.
* Continuous treatment with doxycycline at inclusion.
* Vitamin A treatment in case of intake of 10 000 international unit or more.
* Participation in another research including an exclusion period still in progress at the time of inclusion.
* Under guardianship or curator, or deprived of liberty by a judicial or administrative decision.

Primary outcomes:
measure: For intervention 1 (with or without doxycycline PEP) : 1st occurence of chlamydia or syphilis after the enrolment visit (Day 0)
timeFrame: Month 24
measure: For intervention 2 with or without Bexsero® vaccine : 1st occurence of gonorrhea reported one month after the second vaccine injection
timeFrame: Month 24
Secondary outcomes:
measure: - Occurrence of a first episode of each of the bacterial STIs as well as cumulative incidence of each bacterial STIs
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Occurrence of a new episode of anal or urinary gonorrhoea.
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Occurrence of a first symptomatic episode of chlamydia infection or gonorrhea
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Proportion of patient with Methicillin-Resistant Staphylococcus Aureus and/or doxycycline resistant Staphylococcus aureus from throat. Fecal carriage of Extended-Spectrum Beta-Lactamase-producing Enterobacteriaceae Composition of intestinal microbiota
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Incidence of clinical and biological adverse events
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Proportion of patients taking doxycycline
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Concentration of doxycycline in hair
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Proportion of patients with Antibiotic susceptibilities of all strains of NG (Neisseria gonorrhoeae), CT (chlamydiae trachomatis), MG (mycoplasma genitalium)
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Rate of cured STIs after treatment with or without PEP.
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Incidence of resistance to antibiotics of Neisseria gonorrhoeae with or without doxycycline.
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Incidence of Serum bactericidal activity against meningococcal and gonococcal antigens over time in participants of Bexsero®'s arm.
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Incidence of clinical and biological adverse events following Bexsero® vaccine.
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Prevalence and incidence of meningococcal carriage in pharyngeal, anal and urine swabs.
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Impact of PEP or Bexsero® vaccine on sexual behaviour
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
measure: - Incidence of HIV infection with both prophylaxis strategies.
timeFrame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Bichat
city: Paris
country: France
facility: Hôpital Hôtel Dieu
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital pitié Salpetrière
city: Paris
country: France
facility: Hôpital Pitié-Salpétrière
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Tenon
Study officials:
References: