Doxy-Post-exposure Prophylaxis (DOXY-PEP)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sexually Transmitted Diseases
• Intervention / Treatment: Drug: Doxycycline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Colleen Kelley, MD, MPH; Phone Number: 404-712-1823; Email: colleen.kelley@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Hope Clinic
      • Contact: Colleen Kelley, MD, MPH; Phone Number: 404-712-1823; Email: colleen.kelley@emory.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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:

  1. Systemic immunomodulatory agents
  2. Supraphysiologic doses of steroids (short course steroids less than 7 days duration, allowable at the discretion of the investigators)
  3. Chemotherapy or radiation for treatment of malignancy
  4. 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:

  1. Hgb ≤ 10 g/dL
  2. PTT > 1.5x ULN or INR > 1.5x ULN
  3. Platelet count <100,000

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Doxycycline 100 mg; 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; 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.; Other Names: DOX
Active Comparator: Doxycycline 200 mg; 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; 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.; Other Names: DOX

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood doxycycline concentrations in participants taking 5 doses of doxycycline.	Blood samples will be taken at each in person visit	Throughout study up to 3 months after fifth dose
Changes in urine doxycycline concentrations in participants taking 5 doses of doxycycline.	Urine samples will be taken at each in person visit	Throughout study up to 3 months after fifth dose
Changes in doxycycline concentrations in throat secretions in participants taking 5 doses of doxycycline.	Self-collected swab samples will be collected 24 hours after administration of	Throughout study up to 3 months after fifth dose
Changes in doxycycline concentrations in vaginal secretions in participants taking 5 doses of doxycycline.	Self-collected vaginal swabs will be collected at each in person visit	Throughout study up to 3 months after fifth dose
Changes in doxycycline concentrations in rectal secretions in participants taking 5 doses of doxycycline.	Self-collected and staff assisted vaginal swabs will be collected at each in person visit	Throughout study up to 3 months after fifth dose
Changes in doxycycline concentrations in penile secretions in participants taking 5 doses of doxycycline.	Staff-Assisted urethral and glans swabs will be collected	Throughout study up to 3 months after fifth dose

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Colleen Kelley, MD, MPH, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: May 2, 2023
• First Submitted That Met QC Criteria: May 2, 2023
• First Posted (Actual): May 10, 2023

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: HIV; Prevention; STI; PEP; Post-exposure prophylaxis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Communicable Diseases; Disease Attributes; Urogenital Diseases; Genital Diseases; Sexually Transmitted Diseases; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: STUDY00005552; 75D30122C14484 (Other Grant/Funding Number: Centers for Disease Control and Prevention)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results published for this study (including text, tables, figures, and appendices), will be made available for sharing, after de-identification.
• IPD Sharing Time Frame: The research team will share de-identified participant data after the primary manuscript publication.
• IPD Sharing Access Criteria: Interested investigators can request deidentified data by email for secondary data analyses and/or meta-analyses.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes