Doxy-Post-exposure Prophylaxis

Study Overview
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Brief Summary
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The goal of this project is to collect data regarding the ability of various oral doses of doxycycline to penetrate mucosal tissues in men and women to inform the combination of doxycycline with antiretrovirals (ARVs) for the development of single-dose event-driven multipurpose prevention strategies to protect against HIV and sexually transmitted infections (STIs). This study is of importance in the field of research because it allows the exploration of new dosing strategies that would permit a single event-driven oral dose of medications that could provide protection from HIV as well as other STIs. The study population that this study seeks to enroll are healthy people assigned male or female sex at birth and not using gender-affirming hormone therapy and are willing to undergo study procedures. Recruitment: Both face-to-face and online engagements will be conducted to recruit study participants. Face-to-face locations include bars and nightclubs, community organizations serving study populations, sports events, and community venues, and online engagements include dating sites, social networks, and craigslist, amongst other social medial platforms.

Detailed Description
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The incidence of bacterial STIs is increasing and studies have recently shown that Doxy-PEP can reduce the incidence of bacterial STIs among men who have sex with men (MSM) and Doxy-PEP is being explored for STI prevention among women. A better understanding of mucosal drug penetration of doxycycline will inform the design of future studies to prevent STIs in various populations. The purpose of this study is to understand how well doxycycline taken by mouth gets to the tissues of the rectum and vagina. Researchers think doxycycline could be used to treat sexually transmitted infections (STIs) caused by bacteria. To understand better, they want to see how well doxycycline reaches the tissues affected by STIs. The study procedures include the collection of past and present medical history, and biological specimen sampling such as blood, rectal and vaginal fluids, tissue biopsies, and urine. Study participants will also be administered an investigational agent (doxycycline not yet approved for this indication). The duration of this clinical trial for study participants will be approximately 8 weeks.

Official Title
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Doxy-PEP: Dose-Ranging Study of Persons Receiving Doxycycline

Conditions
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Sexually Transmitted Diseases

Intervention / Treatment
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* Drug: Doxycycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-59 years Assigned male sex or female sex at birth In good general health Not currently taking doxycycline or other tetracycline-derived antibiotics and no plans to initiate during the study For HIV-positive people, on stable antiretroviral therapy with an undetectable viral load and CD4 count> 300ul/ml Willing to use condoms consistently for the duration of the study Able to provide informed consent No plans for relocation in the next 4 months Not pregnant and does not plan on getting pregnant for the duration of the study Willing to undergo peripheral blood, urine, rectal or vaginal secretion collection, and a rectal or vaginal and cervical biopsy procedure Willing to use study products as directed Creatinine clearance >60 ml/min Exclusion Criteria: Currently infected with hepatitis virus and/ or has liver disease Current or chronic history of kidney disease or CrCl<60 ml/min Continued need for, or use during the 90 days prior to enrollment, of the following medications: Systemic immunomodulatory agents Supraphysiologic doses of steroids (short course steroids less than 7 days duration, allowable at the discretion of the investigators) Chemotherapy or radiation for treatment of malignancy Experimental medications, vaccines, or biologicals Intent to use doxycycline or other tetracycline-derived antibiotics during the course of the study, outside of the study procedures Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the study requirements Known allergic reaction to study drugs. Significant laboratory abnormalities at baseline visit for rectal biopsies, including but not limited to: Hgb ≤ 10 g/dL PTT > 1.5x ULN or INR > 1.5x ULN Platelet count <100,000

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Doxycycline 100 mg<br>Doxycycline 100mg Participants will receive the first assigned dose of Doxycycline at the clinic on days 0 and 3 at the clinic. The other three doses of the medication will be taken at home on days 7 and 1 | Drug: Doxycycline<br>* Doxycycline is used to treat or prevent infections that are strongly suspected to be caused by bacteria; it is an antimicrobial drug indicated for bacterial infections such as sexually transmitted infections. Doxycycline (DOX) will be given orally at 100 and 200 mg doses.<br>* Other names: DOX;|
| Active Comparator: Doxycycline 200 mg<br>Doxycycline - 200 mg Participants will receive the first assigned dose of Doxycycline at the clinic on days 0 and 3 at the clinic. The other three doses of the medication will be taken at home on days 7 and 10 | Drug: Doxycycline<br>* Doxycycline is used to treat or prevent infections that are strongly suspected to be caused by bacteria; it is an antimicrobial drug indicated for bacterial infections such as sexually transmitted infections. Doxycycline (DOX) will be given orally at 100 and 200 mg doses.<br>* Other names: DOX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Doxycycline concentrations in rectal tissues | Self-collected swabs and rectal biopsies will be collected 24 hours after administration of the initial dose of doxycycline | Day 2 | 
| Doxycycline concentrations in vaginal tissues | Self-collected swabs and vaginal biopsies will be collected 24 hours after administration of the initial dose of doxycycline | Day 2 | 
| Doxycycline concentrations in rectal tissues after the fifth dose of doxycycline | Self-collected swabs and rectal biopsies will be collected 24 hours after administration of the fifth dose of doxycycline | Day 15 | 
| Doxycycline concentrations in vaginal tissues collected 24 hours after the fifth dose of doxycycline | Self-collected swabs and vaginal biopsies will be collected 24 hours after administration of the fifth dose of doxycycline | Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prevention, STI, Post-exposure prophylaxis, HIV, PEP