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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)

Primary Purpose

Unsafe Sex, Risk-Taking

Status

Active

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Experimental: doxycycline

Bexsero® vaccine

About this trial

This is an interventional treatment trial for Unsafe Sex focused on measuring STI infection, PREVENTION

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleAccepts Healthy Volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

No Intervention

Arm Label

doxycycline and Bexsero® vaccine

doxycycline

Bexsero® vaccine

No treatment

Arm Description

-doxycycline will be taken by participants as PEP (prophylaxy post exposition) and participants will received Meningococcal B vaccine (Bexsero®) at D0 and M2

-doxycycline will be taken by participants as PEP (prophylaxy post exposition)

-Meningococcal B vaccine (Bexsero®) at D0 and M2

-no doxycycline and no Bexsero® vaccine

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

- 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.

- 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.

- 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.

- 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

- Incidence of clinical and biological adverse events

Proportion of patients experiencing a clinical or biological adverse events (ANRS scale)

- Proportion of patients taking doxycycline

Adherence will be evaluated by doxycycline pills taken by patients

- Concentration of doxycycline in hair

Adherence will be evaluated by détection of doxycyclin in hair

- 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)

- Rate of cured STIs after treatment with or without PEP.

declaration of illnesses from infection to healing

- 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

- 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

- 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)

- 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

- 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

- Incidence of HIV infection with both prophylaxis strategies.

HIV infection will be tested by serology and western blot assay

Full Information

NCT ID

NCT04597424

First Posted

October 1, 2020

Last Updated

August 24, 2023

Sponsor

ANRS, Emerging Infectious Diseases

1. Study Identification

Unique Protocol Identification Number

NCT04597424

Brief 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)

Acronym

DOXYVAC

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

January 19, 2021 (Actual)

Primary Completion Date

February 19, 2023 (Actual)

Study Completion Date

September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ANRS, Emerging Infectious Diseases

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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".

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Unsafe Sex, Risk-Taking

Keywords

STI infection, PREVENTION

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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

Masking

None (Open Label)

Allocation

Randomized

Enrollment

556 (Actual)

8. Arms, Groups, and Interventions

Arm Title

doxycycline and Bexsero® vaccine

Arm Type

Experimental

Arm Description

-doxycycline will be taken by participants as PEP (prophylaxy post exposition) and participants will received Meningococcal B vaccine (Bexsero®) at D0 and M2

Arm Title

doxycycline

Arm Type

Experimental

Arm Description

-doxycycline will be taken by participants as PEP (prophylaxy post exposition)

Arm Title

Bexsero® vaccine

Arm Type

Experimental

Arm Description

-Meningococcal B vaccine (Bexsero®) at D0 and M2

Arm Title

No treatment

Arm Type

No Intervention

Arm Description

-no doxycycline and no Bexsero® vaccine

Intervention Type

Drug

Intervention Name(s)

Experimental: doxycycline

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Bexsero® vaccine

Intervention Description

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

Primary Outcome Measure Information:

Title

For intervention 1 (with or without doxycycline PEP) : 1st occurence of chlamydia or syphilis after the enrolment visit (Day 0)

Description

Time Frame

Month 24

Title

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

Description

Time Frame

Month 24

Secondary Outcome Measure Information:

Title

- Occurrence of a first episode of each of the bacterial STIs as well as cumulative incidence of each bacterial STIs

Description

Time Frame