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) (DOXYVAC)

August 24, 2023 updated by: ANRS, Emerging Infectious Diseases
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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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".

Study Type

Interventional

Enrollment (Actual)

556

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75970
        • Hôpital Tenon
      • Paris, France, 75651
        • Hopital Pitie Salpetriere
      • Paris, France, 75908
        • Hôpital Européen Georges Pompidou
      • Paris, France, 75475
        • Hôpital Saint-Louis
      • Paris, France, 75743
        • Hôpital Necker-Enfants Malades
      • Paris, France, 75571
        • Hopital Saint-Antoine
      • Paris, France, 75651
        • Hôpital Pitié-Salpêtrière
      • Paris, France, 75181
        • Hôpital Hotel Dieu
      • Paris, France, 75000
        • Hopital Bichat

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: doxycycline and Bexsero® vaccine
-doxycycline will be taken by participants as PEP (prophylaxy post exposition) and participants will received Meningococcal B vaccine (Bexsero®) at D0 and M2
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.
Experimental: doxycycline
-doxycycline will be taken by participants as PEP (prophylaxy post exposition)
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.
Experimental: Bexsero® vaccine
-Meningococcal B vaccine (Bexsero®) at D0 and M2
Biological: Bexsero® vaccine
1st injection of Bexsero® vaccine at inclusion visit, 2nd injection at week 8.
No Intervention: No treatment
-no doxycycline and no Bexsero® vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
For intervention 1 (with or without doxycycline PEP) : 1st occurence of chlamydia or syphilis after the enrolment visit (Day 0)
Time Frame: Month 24

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
For intervention 2 with or without Bexsero® vaccine : 1st occurence of gonorrhea reported one month after the second vaccine injection
Time Frame: Month 24

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
- Occurrence of a first episode of each of the bacterial STIs as well as cumulative incidence of each bacterial STIs
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24

- 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
- Occurrence of a new episode of anal or urinary gonorrhoea.
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
- 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
- Occurrence of a first symptomatic episode of chlamydia infection or gonorrhea
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24

- 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
- 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
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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
- Incidence of clinical and biological adverse events
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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
- Proportion of patients taking doxycycline
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Adherence will be evaluated by doxycycline pills taken by patients
Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
- Concentration of doxycycline in hair
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
Adherence will be evaluated by détection of doxycyclin in hair
Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
- Proportion of patients with Antibiotic susceptibilities of all strains of NG (Neisseria gonorrhoeae), CT (chlamydiae trachomatis), MG (mycoplasma genitalium)
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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
- Rate of cured STIs after treatment with or without PEP.
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
declaration of illnesses from infection to healing
Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
- Incidence of resistance to antibiotics of Neisseria gonorrhoeae with or without doxycycline.
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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
- Incidence of Serum bactericidal activity against meningococcal and gonococcal antigens over time in participants of Bexsero®'s arm.
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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
- Incidence of clinical and biological adverse events following Bexsero® vaccine.
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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
- Prevalence and incidence of meningococcal carriage in pharyngeal, anal and urine swabs.
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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
- Impact of PEP or Bexsero® vaccine on sexual behaviour
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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
- Incidence of HIV infection with both prophylaxis strategies.
Time Frame: Month 2, Month 3, Month 6, Month 12, Month 18, Month 21, Month 24
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ANRS, Emerging Infectious Diseases

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 19, 2021

Primary Completion (Actual)

February 19, 2023

Study Completion (Estimated)

September 1, 2023

Study Registration Dates

First Submitted

October 1, 2020

First Submitted That Met QC Criteria

October 15, 2020

First Posted (Actual)

October 22, 2020

Study Record Updates

Last Update Posted (Actual)

August 25, 2023

Last Update Submitted That Met QC Criteria

August 24, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANRS 174 DOXYVAC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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