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Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens

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ClinicalTrials.gov Identifier: NCT03976752
Recruitment Status : Recruiting
First Posted : June 6, 2019
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Colleen Kelley, Emory University

Brief Summary:
This study is being conducted to determine if the uptake of anti-HIV medication, called Genvoya®, at different time-frames, is different at several body sites, including mucosal tissues. This medication might be considered for on-demand PEP regimens in the future.

Condition or disease Intervention/treatment Phase
HIV/AIDS Drug: Genvoya Phase 1

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 another anti-HIV medication, called Genvoya®, at different time-frames, is different at several body sites, including mucosal tissues. This medication might be considered for on-demand PEP regimens in the future.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 62 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Body Compartment Pharmacokinetics of Anti-retroviral Agents That May be Considered for Future On-demand Peri-exposure HIV Prophylaxis Regimens
Actual Study Start Date : March 13, 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
No Intervention: Pre-drug
Participants enrolled in the pre-drug arm will not receive any drug. At visit 2, they will undergo blood, urine, penile swab, cheek swab, rectal swab and rectal biopsy collection.
Experimental: Genvoya - 2 and 48 hours specimen collection
Specimen collection 2 hours after taking the medication in the clinic (visit 4), and 48 hours after taking the medication in the clinic (visit 5).
Drug: Genvoya

Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat).

At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24hrs after home dosing, participants will be given another single dose of Genvoya at the clinic.

Other Name: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide

Experimental: Genvoya - 4 and 72 hours specimen collection
Specimen collection 4 hours after taking the medication in the clinic (visit 4), and 72 hours after taking the medication in the clinic (visit 5).
Drug: Genvoya

Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat).

At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24hrs after home dosing, participants will be given another single dose of Genvoya at the clinic.

Other Name: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide

Experimental: Genvoya - 24 and 96 hours specimen collection
Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96hrs after taking the medication in the clinic (visit 5).
Drug: Genvoya

Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat).

At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24hrs after home dosing, participants will be given another single dose of Genvoya at the clinic.

Other Name: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide

Experimental: Genvoya - Single time point specimen collection
Specimen collection 8 hours after taking the medication in the clinic (visit 4).
Drug: Genvoya

Genvoya is a fixed-dose combination anti-retroviral drug containing tenofovir alafenamide (TAF), emtricitabine (FTC), elvitegravir (EVG), and cobicistat).

At the second study visit, participants will be provided with a single dose of Genvoya, and instructed to take the dose at home with documentation by digital, time-stamped photo or video. At the third study visit, which will occur 24hrs after home dosing, participants will be given another single dose of Genvoya at the clinic.

Other Name: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide




Primary Outcome Measures :
  1. Change in plasma median drug levels between baseline and study visit follow-up visits [ Time Frame: Baseline, and 2, 4, 8, 18, 24, 48, 72, 96 hours after taking the medication ]
    Median (range) drug levels will be calculated at baseline and each of the protocol specified follow-up time points. Differences in median drug levels between baseline and follow-up visits will be analyzed with non-parametric Wilcoxon-signed rank tests. A p-value of <0.05 will be considered significant.


Secondary Outcome Measures :
  1. Change in peripheral blood mononuclear cell (PBMC) median drug levels between baseline and study visit follow-up visits [ Time Frame: Baseline, and 2, 4, 8, 18, 24, 48, 72, 96 hours after taking the medication ]
    A peripheral blood mononuclear cell (PBMC) is any peripheral blood cell having a round nucleus: lymphocytes (T cells, B cells, NK cells) and monocytes. Median (range) drug levels will be calculated at baseline and each of the protocol specified follow-up time points. Differences in median drug levels between baseline and follow-up visits will be analyzed with non-parametric Wilcoxon-signed rank tests. A p-value of <0.05 will be considered significant.


Other Outcome Measures:
  1. Change in rectal tissues median drug levels between baseline and study visit follow-up visits [ Time Frame: Baseline, and 2, 4, 8, 18, 24, 48, 72, 96 hours after taking the medication ]
    Median (range) drug levels will be calculated at baseline and each of the protocol specified follow-up time points. Differences in median drug levels between baseline and follow-up visits will be analyzed with non-parametric Wilcoxon-signed rank tests. A p-value of <0.05 will be considered significant.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   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.
  10. Hepatitis B surface antigen (HBsAg) must be negative (screening lab test)
  11. Creatine clearance >60 ml/min

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. Currently infected with hepatitis virus and/ or have liver disease
  3. Current or chronic history of kidney disease
  4. 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
    5. HBsAg reactive
  5. 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
  6. 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
  7. 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. Experimental medications, vaccines, or biologicals
  8. Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures
  9. Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, discharge, bleeding, etc.)
  10. Current use of hormonal therapy
  11. 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.
  12. Participants taking potent inhibitors (e.g. itraconazole, diltiazem) or inducers (e.g. rifampin, phenytoin) of the CYP3A4 enzyme that also metabolizes Genvoya will be excluded from the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03976752


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

Locations
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United States, Georgia
Hope Clinic Recruiting
Atlanta, Georgia, United States, 30322
Contact: Colleen Kelley, MD    404-712-1823    colleen.kelley@emory.edu   
Principal Investigator: Colleen Kelley, MD         
Sponsors and Collaborators
Emory University
Investigators
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Principal Investigator: Colleen Kelley, MD Emory University
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Responsible Party: Colleen Kelley, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03976752    
Other Study ID Numbers: IRB00108386
First Posted: June 6, 2019    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data that underlie the results reported in this article, after de-identification (e.g., text, tables, figures, and appendices), will be available. The study protocol will be available. Data will become available Beginning 9 months and ending at 36 months following publication to researchers who provide a methodologically sound proposal.
Supporting Materials: Study Protocol
Time Frame: Data will become available beginning 9 months and ending at 36 months following article publication.
Access Criteria: Proposals should be directed to colleen.kelley@emory.edu. To gain access, data requestors will need to sign a data access agreement.

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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:
HIV
MSM
Anti-retrovirals
Pharmacokinetics
Peri-exposure HIV prophylaxis
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Emtricitabine
Cobicistat
Genvoya
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors