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)

Risk-Taking Clinical Trial

— DOXYVAC  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04597424
• Other study ID #: ANRS 174 DOXYVAC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 19, 2021
• Est. completion date: September 2023

Study information

• Verified date: August 2023
• Source: ANRS, Emerging Infectious Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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".

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 556
• Est. completion date: September 2023
• Est. primary completion date: February 19, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infections
• Risk-Taking
• Sexually Transmitted Diseases
• Unsafe Sex

Intervention

Drug:
• Experimental: doxycycline
2 tablets of doxycycline 100 mg (monohydrate form) will be taken orally after each risk sexual intercourse, ideally within 24 hours after sex and no more than 72 hours. PEP should not be taken more than 3 times over a 7 days' period. If a participant has risk sexual intercourse for several consecutive days, PEP should be taken at least 48 hours apart and no more than 3 times 2 tablets over 7 days. A maximum of 3 intakes of 2 tablets will be allowed over a period of 7 days.

Biological:
• Bexsero® vaccine
1st injection of Bexsero® vaccine at inclusion visit, 2nd injection at week 8.

Locations

Country	Name	City	State
France	Hôpital Bichat	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Hôtel Dieu	Paris
France	Hôpital Necker-Enfants Malades	Paris
France	Hôpital pitié Salpetrière	Paris
France	Hôpital Pitié-Salpétrière	Paris
France	Hôpital Saint-Antoine	Paris
France	Hôpital Saint-Louis	Paris
France	Hôpital Tenon	Paris

Sponsors (1)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For intervention 1 (with or without doxycycline PEP) : 1st occurence of chlamydia or syphilis after the enrolment visit (Day 0)	Intervention 1 (with or without doxycycline PEP) is the first episode of chlamydia or syphilis after the enrolment visit (Day 0) (chlamydia and syphilis diagnosed at the enrolment visit will not be included in the primary endpoint).; Chlamydia détection will be performed by polymerase chain reaction.Syphilis détection will be performed by antigen.	Month 24
Primary	For intervention 2 with or without Bexsero® vaccine : 1st occurence of gonorrhea reported one month after the second vaccine injection	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.; Gonorrhea détection will be performed by polymerase chain reaction.	Month 24
Secondary	- Occurrence of a first episode of each of the bacterial STIs as well as cumulative incidence of each bacterial STIs	- 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.; Chlamydia détection will be performed by polymerase chain reaction. Syphilis détection will be performed by antigen.; Mycoplasma genitalium be performed by polymerase chain reaction. Gonorrhea détection will be performed by polymerase chain reaction.	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Occurrence of a new episode of anal or urinary gonorrhoea.	- Occurrence of a new episode of anal or urinary gonorrhoea. Gonorrhea détection will be performed by polymerase chain reaction.	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Occurrence of a first symptomatic episode of chlamydia infection or gonorrhea	- Occurrence of a first symptomatic episode of chlamydia infection or gonorrhea at urinary or anal sites.; Chlamydia détection will be performed by polymerase chain reaction. Gonorrhea détection will be performed by polymerase chain reaction.	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- 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	detection from throat swab of carriage of MRSA (methicillin-resistant Staphylococcus aureus) and/or doxycycline resistant Staphylococcus aureus, fecal carriage of ESBL (extended-spectrum beta-lactamase) -producing Enterobacteriaceae, and composition of the intestinal microbiota), all détected by polymerase chain reaction assay	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Incidence of clinical and biological adverse events	Proportion of patients experiencing a clinical or biological adverse events (ANRS scale)	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Proportion of patients taking doxycycline	Adherence will be evaluated by doxycycline pills taken by patients	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Concentration of doxycycline in hair	Adherence will be evaluated by détection of doxycyclin in hair	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Proportion of patients with Antibiotic susceptibilities of all strains of NG (Neisseria gonorrhoeae), CT (chlamydiae trachomatis), MG (mycoplasma genitalium)	identification of Antibiotic susceptibilities of all strains of NG (Neisseria gonorrhoeae), CT (chlamydiae trachomatis), MG (mycoplasma genitalium) to doxycycline, macrolides, fluoroquinolones and third generation cephalosporin will be performed by PCR (polymerase chain reaction assay)	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Rate of cured STIs after treatment with or without PEP.	declaration of illnesses from infection to healing	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Incidence of resistance to antibiotics of Neisseria gonorrhoeae with or without doxycycline.	Proportion of participants with resistance to antibiotics of Neisseria gonorrhoeae will be evaluated by polymerase chain reaction to detect mutations	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Incidence of Serum bactericidal activity against meningococcal and gonococcal antigens over time in participants of Bexsero®'s arm.	Proportion of participants with Serum bactericidal activity against meningococcal and gonococcal antigens	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Incidence of clinical and biological adverse events following Bexsero® vaccine.	Proportion of participants experiencing a clinical and biological adverse events following Bexsero® vaccine (ANRS scale)	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Prevalence and incidence of meningococcal carriage in pharyngeal, anal and urine swabs.	detection of meningococcal carriage in pharyngeal, anal and urine swabs will be performed	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- 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	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Secondary	- Incidence of HIV infection with both prophylaxis strategies.	HIV infection will be tested by serology and western blot assay	Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24