Clinical Trials

MainTitle

Body Compartment Pharmacokinetics of Anti- Retroviral Agents That May be Used for Future HIV Post- Exposure Prophylaxis. (PEP2)

This study is currently recruiting participants. (see Contacts and Locations)

Verified February 2019 by Colleen Kelley, Emory University

Sponsor
Emory University

Collaborator
Centers for Disease Control and Prevention

Information provided by (Responsible Party)
Colleen Kelley, Emory University

ClinicalTrials.gov Identifier
NCT03472963

First received: March 15, 2018
Last updated: February 6, 2019
Last Verified: February 2019
History of Changes
Purpose

Purpose

This study is being conducted to determine if the uptake of anti-HIV medications called Genvoya® and darunavir is different at several body sites, including mucosal tissues.

Condition Intervention Phase
HIV Infections

Drug : Single dose of Genvoya® and a single 800 mg dose of Darunavir®
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Used for Future HIV Post-exposure Prophylaxis Regimens.

Further study details as provided by Colleen Kelley, Emory University:

Primary Outcome Measures

  • Median Genvoya plasma concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Approximately 24 mL of blood will be drawn to obtain Genvoya plasma concentration (median + range; ng/mL)
  • Median Darunavir plasma concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Approximately 24 mL of blood will be drawn to obtain Darunavir plasma concentration (median + range; ng/mL)
  • Median Genvoya rectal tissue distribution [ Time Frame: 2 to up to 96 hours after time of dose ]
    Rectal biopsy via rigid sigmoidoscopy will be performed to obtain Genvoya rectal tissue distribution (median + range; ng/mg of tissue).
  • Median Darunavir rectal tissue distribution [ Time Frame: 2 to up to 96 hours after time of dose ]
    Rectal biopsy via rigid sigmoidoscopy will be performed to obtain Darunavir rectal tissue distribution (median + range; ng/mg of tissue).
Secondary Outcome Measures:
  • Median Genvoya rectal secretion concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Rectal swabs for Genvoya rectal secretion concentration (median + range; ng/swab)
  • Median Darunavir rectal secretion concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Rectal swabs for Darunavir rectal secretion concentration (median + range; ng/swab)
  • Median Genvoya urethral secretion concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Urethral swab for Genvoya urethral secretion concentration (median + range; ng/swab)
  • Median Darunavir urethral secretion concentration [ Time Frame: 2 to up to 96 hours after time of dose ]
    Urethral swab for Darunavir urethral secretion concentration (median + range; ng/swab)

Estimated Enrollment: 58
Study Start Date: April 27, 2018
Estimated Study Completion Date: December 15, 2019
Estimated Primary Completion Date: December 15, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
No Intervention: Pre- drug
Participants will not receive any drug. They will be asked to return 1-6 weeks after the screening visit for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, rectal swabs, urine sample, and rectal biopsy via rigid sigmoidoscopy.
Experimental: Group A.1
Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 2 hours, 24 hours (+/- 1 hour), and 72 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 2 hours after dosing.
Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

Experimental: Group A.2
Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 2 hours, 24 hours (+/- 1 hour), and 72 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 24 hours after dosing.
Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

Experimental: Group A.3
Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 2 hours, 24 hours (+/- 1 hour), and 72 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 72 hours after dosing.
Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

Experimental: Group B.1
Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 4 hours, 48 hours (+/- 1 hour), and 96 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 4 hours after dosing.
Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

Experimental: Group B.2
Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 4 hours, 48 hours (+/- 1 hour), and 96 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 48 hours after dosing.
Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

Experimental: Group B.3
Men will be dosed with Genvoya and Darunavir® on site (time of dose will be recorded) and asked to return in 4 hours, 48 hours (+/- 1 hour), and 96 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 96 hours after dosing.
Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

Experimental: Group C
Participants will be given a one- day supply of with Genvoya and Darunavir®. Participants return 8 hours (+/- 30min window), 24 hours (+/- 1 hr), and 48 hours (+/- 1 hour) after taking dose for study procedures (blood collection, oral cheek swab, penile swabs, urethral swab, and a urine sample). Participant will undergo rectal swabs and rectal biopsy via rigid sigmoidoscopy in 8 hours after taking the medication.
Drug: Single dose of Genvoya® and a single 800 mg dose of Darunavir®

Men will be instructed to take Single dose of Genvoya® and a single 800 mg dose of Darunavir® per oral

Detailed Description:

Men who have sex with men (MSM) continue to be disproportionately affected by HIV. The majority of MSM acquire HIV after exposure to the rectal mucosa through unprotected receptive anal intercourse. Post-exposure-prophylaxis (PEP) is an intervention that is used to prevent HIV infection soon (72 hours) after a potential exposure. HIV-negative people with a possible exposure to HIV are instructed to take 28 days of a combination anti-HIV medication regimen, Truvada® + Raltegravir. This study is being conducted to determine if the uptake of other anti-HIV medications called Genvoya® and darunavir is different at several body sites, including mucosal tissues. These other medications might be considered for PEP regimens in the future.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 49 Years  
Sexes Eligible for Study: Male  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

    1. HIV-negative man who reports receptive anal sex with another man in the last 6 months
    2. Aged 18-49 years
    3. Not currently taking PrEP and no plans to initiate during study
    4. Not currently taking PEP
    5. Able to provide informed consent in English
    6. No plans for relocation in the next 3 months
    7. Willing to undergo peripheral blood, penile swabs, urine, and rectal biopsy sampling
    8. Willing to use study products as directed
    9. Willing to abstain from receptive anal intercourse 3 days prior to starting study product and for the duration of the study and for 7 days after any rectal biopsy procedure.


Exclusion Criteria:
    1. History of inflammatory bowel disease or other inflammatory, infiltrative, infectious or vascular condition involving the lower gastrointestinal tract that, in the judgment of the investigators, may be worsened by study procedures or may significantly distort the anatomy of the distal large bowel
    2. Significant laboratory abnormalities at baseline visit, 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
        4. Creatinine clearance <60
      1. Any known medical condition that, in the judgment of the investigators, increases the risk of local or systemic complications of endoscopic procedures or pelvic examination, including but not limited to:
          1. Uncontrolled or severe cardiac arrhythmia
          2. Recent major abdominal, cardiothoracic, or neurological surgery
          3. History of uncontrolled bleeding diathesis
          4. History of colonic, rectal, or vaginal perforation, fistula, or malignancy
          5. History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal mucosa, or untreated sexually transmitted disease with mucosal involvement
        1. Continued need for, or use during the 14 days prior to enrollment, of the following medications:
            1. Aspirin or more than 4 doses of NSAIDs
            2. Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
            3. Any form of rectally administered agent besides lubricants or douching used for sexual intercourse
          1. 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
              3. Experimental medications, vaccines, or biologicals
            1. Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures
            2. Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, discharge, bleeding, etc.)
            3. Current use of hormonal therapy
            4. 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.

          contacts and locations

          Contacts and Locations

          Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

          Please refer to this study by its ClinicalTrials.gov identifier: NCT03472963

          Contacts

          Contact:   Colleen Kelley, MD, MPH 404-712-1823 colleen.kelley@emory.edu

          Locations

          United States, Georgia
          Emory University Recruiting
          Atlanta, Georgia, United States, 30322
          Contact: Colleen Kelley, MD, MPH    404-712-1823    colleen.kelley@emory.edu

          Sponsors and Collaborators

          Emory University
          Centers for Disease Control and Prevention

          Investigators

          Principal Investigator: Colleen Kelley, MD, MPH Emory University
          More Information

          More Information


          Responsible Party: Colleen Kelley, Associate Professor, Emory University  
          ClinicalTrials.gov Identifier: NCT03472963   History of Changes  
          Other Study ID Numbers: IRB00101179  
          Study First Received: March 15, 2018  
          Last Updated: February 6, 2019  

          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.: No  

          Keywords provided by Colleen Kelley, Emory University:

          Post-Exposure Prophylaxis
          Anti-Retroviral
          Pharmacokinetics

          Additional relevant MeSH terms:
          HIV Infections
          Darunavir
          Genvoya

          ClinicalTrials.gov processed this data on August 11, 2020
          This information is provided by ClinicalTrials.gov.