ARTPhase 4NCT04039217
Antiretroviral Therapy (ART) Persistence in Different Body Compartments in HIV Negative MSM
A Phase 4 study testing Biktarvy in people with ART and HIV, run by Emory University at 1 site in United States.
Trial summary
The study seeks to understand how anti-HIV drug Biktarvy, which contains the drugs tenofovir alafenamide (TAF), emtricitabine (FTC), and bictegravir (BIC) is absorbed and how long it persists in different body compartments, including mucosal tissues, as it may be considered for PrEP or PEP regimens in the future. Read more about this study
- Who is it for?
- Ages 18 to 49 years, men only
- What is being tested?
- Biktarvy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2019to 28 Aug 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 49 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- HIV-negative man who reports receptive anal sex with another man in the last 6 months
- Aged 18-49 years
- Not currently taking PrEP and no plans to initiate during study
- Not currently taking PEP
- Able to provide informed consent in English
- No plans for relocation in the next 3 months
Show all 11Show fewer
- Willing to undergo peripheral blood, penile swabs, urine, and rectal biopsy sampling
- Willing to use study products as directed
- 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.
- Hepatitis B surface antigen (HBsAg) must be negative (screening lab test)
- Creatine clearance >60 ml/min
Who cannot join
- 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
- Currently infected with hepatitis virus and/ or have liver disease
- Current or chronic history of kidney disease
- Significant laboratory abnormalities at baseline visit, including but not limited to:
- Hgb ≤ 10 g/dL
- partial thromboplastin time (PTT) > 1.5x upper limit of normal (ULN) or international normalized ratio (INR) > 1.5x ULN
Show all 28Show fewer
- Platelet count <100,000
- Creatinine clearance <60
- HBsAg reactive
- 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:
- Uncontrolled or severe cardiac arrhythmia
- Recent major abdominal, cardiothoracic, or neurological surgery
- History of uncontrolled bleeding diathesis
- History of colonic, rectal, fistula, or malignancy
- History or evidence on clinical examination of ulcerative, suppurative, or proliferative lesions of the anorectal mucosa, or untreated sexually transmitted disease with mucosal involvement
- Continued need for, or use during the 14 days prior to enrollment, of the following medications:
- Aspirin or more than 4 doses of NSAIDs
- Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents
- Any form of rectally administered agent besides lubricants or douching used for sexual intercourse
- 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)
- Experimental medications, vaccines, or biologicals
- Intent to use HIV antiretroviral pre/post-exposure prophylaxis (PrEP or PEP) during the study, outside of the study procedures
- Symptoms of an untreated rectal sexually transmitted infection (e.g. rectal pain, discharge, bleeding, etc.)
- Current use of hormonal therapy
- 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.
- Participants taking potent inhibitors (e.g. itraconazole, diltiazem) or inducers (e.g. rifampin, phenytoin) of the CYP3A4 enzyme will be excluded from the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: ART Persistence: Antiretroviral Drug Persistence in Different Body Compartments in HIV Negative Men Who Have Sex With Men
The study seeks to understand how anti-HIV drug Biktarvy, which contains the drugs tenofovir alafenamide (TAF), emtricitabine (FTC), and bictegravir (BIC) is absorbed and how long it persists in different body compartments, including mucosal tissues, as it may be considered for PrEP or PEP regimens in the future.
Read the 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 receptive anal intercourse without condoms. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are recommended for MSM who may be exposed to HIV to prevent infection. Current recommendations for PrEP are to take the combination anti-HIV drug, tenofovir+emtricitabine (TDF/FTC), on a daily basis for the duration of someone's HIV risk exposure period, which could be months or years. For PEP, a three-drug anti-HIV medication is recommended within 72 hours of a possible exposure for a 28-day course. While PrEP and PEP are effective, some people find it difficult to follow the recommended regimen. Therefore, additional short-course dosing regimens for PrEP and PEP are being considered for future development. The study drug provided in this study will not protect participants from HIV or treat any active infection. This proposal seeks to understand how other anti-HIV medications are absorbed and how long they persist in different body compartments, including mucosal tissues, as they may be considered for PrEP or PEP regimens in the future.
Participants will be sequentially enrolled into study arms. All participants will take two doses of Biktarvy and then will have biological samples collected at different time points. Blood will be collected at three different time points and a rectal biopsy will occur once. Participants may participate in more than one study arm or subgroup; however, at least 6 weeks must lapse after completion of one study arm or subgroup, before entry into another.
Median drug levels of TAF, FTC, and BIC in plasma, peripheral blood mononuclear cells (PBMCs) and rectal tissues will be calculated at baseline, 24 hours after the first dose and 120 hours after the first dose as the primary outcomes of this study. Samples collected at other time points will be stored for future exploratory analyses.
- Being tested
- Biktarvy
- Keywords
- PrEP, PEP, MSM, Short-course regimen, Pharmacokinetics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiktarvyDrug
Also called BIC/FTC/TAF
Participants will be given two doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours. The first dose is given in the clinic and participants are instructed to take the second dose at home, 24 hours after the first dose.
| Study group | Role | What they receive |
|---|---|---|
| Sample collection 2, 48, and 96 hours after first dose of Biktarvy | Experimental | Participants in this study arm (Arm A) will provide biological specimens 2, 48, and 96 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits. Receives: Drug: Biktarvy |
| Sample collection 4, 26, and 120 hours after first dose of Biktarvy | Experimental | Participants in this study arm (Arm B) will provide biological specimens 4, 26, and 120 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits. Receives: Drug: Biktarvy |
| Sample collection 24, 28, and 72 hours after first dose of Biktarvy | Experimental | Participants in this study arm (Arm C) will provide biological specimens 24, 28, and 72 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits. Receives: Drug: Biktarvy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Drug Levels in Plasma
Median drug levels of tenofovir (TFV), emtricitabine (FTC), and bictegravir (BIC) in plasma were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are plasma concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.
Measured: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs)
Median drug concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in PBMCs were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are PBMC concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.
Measured: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose
Median Drug Levels in Rectal Tissues
Median drug levels of TFV, FTC, and BIC in rectal tissue were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are rectal tissue concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.
Measured: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2019
- Study start30 Sep 2019
- Primary completion28 Aug 2020
- Study completion28 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for ARTStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Colleen Kelley, Emory University
- Investigators
- Colleen Kelley, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04039217
- Sponsor's protocol ID
- IRB00111410
- Status last verified
- Jan 2022
- First submitted
- 29 Jul 2019
- Last updated
- 22 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after de-identification (e.g., text, tables, figures, and appendices), will be available for sharing.
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ART Persistence: Antiretroviral Drug Persistence in Different Body Compartments in HIV Negative Men Who Have Sex With Men
- ClinicalTrials.gov ID
- NCT04039217
- Acronym / sponsor ID
- IRB00111410
- Keywords
- PrEP, PEP, MSM, Short-course regimen, Pharmacokinetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 30 Sep 2019 (actual)
- Primary completion
- 28 Aug 2020 (actual)
- Study completion
- 28 Aug 2020 (actual)
- First posted
- 31 Jul 2019 (actual)
- Results
- Posted 22 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study seeks to understand how anti-HIV drug Biktarvy, which contains the drugs tenofovir alafenamide (TAF), emtricitabine (FTC), and bictegravir (BIC) is absorbed and how long it persists in different body compartments, including mucosal tissues, as it may be considered for PrEP or PEP regimens in the future.
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 receptive anal intercourse without condoms. Pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are recommended for MSM who may be exposed to HIV to prevent infection. Current recommendations for PrEP are to take the combination anti-HIV drug, tenofovir+emtricitabine (TDF/FTC), on a daily basis for the duration of someone's HIV risk exposure period, which could be months or years. For PEP, a three-drug anti-HIV medication is recommended within 72 hours of a possible exposure for a 28-day course. While PrEP and PEP are effective, some people find it difficult to follow the recommended regimen. Therefore, additional short-course dosing regimens for PrEP and PEP are being considered for future development. The study drug provided in this study will not protect participants from HIV or treat any active infection. This proposal seeks to understand how other anti-HIV medications are absorbed and how long they persist in different body compartments, including mucosal tissues, as they may be considered for PrEP or PEP regimens in the future.
Participants will be sequentially enrolled into study arms. All participants will take two doses of Biktarvy and then will have biological samples collected at different time points. Blood will be collected at three different time points and a rectal biopsy will occur once. Participants may participate in more than one study arm or subgroup; however, at least 6 weeks must lapse after completion of one study arm or subgroup, before entry into another.
Median drug levels of TAF, FTC, and BIC in plasma, peripheral blood mononuclear cells (PBMCs) and rectal tissues will be calculated at baseline, 24 hours after the first dose and 120 hours after the first dose as the primary outcomes of this study. Samples collected at other time points will be stored for future exploratory analyses.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sample collection 2, 48, and 96 hours after first dose of Biktarvy | Experimental | Drug: BiktarvyParticipants in this study arm (Arm A) will provide biological specimens 2, 48, and 96 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits. |
| Sample collection 4, 26, and 120 hours after first dose of Biktarvy | Experimental | Drug: BiktarvyParticipants in this study arm (Arm B) will provide biological specimens 4, 26, and 120 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits. |
| Sample collection 24, 28, and 72 hours after first dose of Biktarvy | Experimental | Drug: BiktarvyParticipants in this study arm (Arm C) will provide biological specimens 24, 28, and 72 hours after the in-clinic dose of Biktarvy. Approximately 24 mL of blood will be drawn, an oral cheek swab, 1 pre-wet penile swab and 1 dry penile swab, and a urethral swab will be collected. After previous swab collections are complete, participants will be asked to provide a urine sample (some of which will be used for gonorrhea and chlamydia testing). Participants will undergo rectal biopsy collection at one of the study visits. |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- HIV-negative man who reports receptive anal sex with another man in the last 6 months
- Aged 18-49 years
- Not currently taking PrEP and no plans to initiate during study
- Not currently taking PEP
- Able to provide informed consent in English
Key exclusion criteria (28 listed)
- 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
- Currently infected with hepatitis virus and/ or have liver disease
- Current or chronic history of kidney disease
- Significant laboratory abnormalities at baseline visit, including but not limited to:
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiktarvyAlso: BIC/FTC/TAFParticipants will be given two doses of the oral fixed dose combination anti-HIV medication Biktarvy (BIC/FTC/TAF) separated by 24 hours. The first dose is given in the clinic and participants are instructed to take the second dose at home, 24 hours after the first dose. | Drug | Sample collection 2, 48, and 96 hours after first dose of Biktarvy, Sample collection 24, 28, and 72 hours after first dose of Biktarvy, Sample collection 4, 26, and 120 hours after first dose of Biktarvy |
Primary outcome
Median Drug Levels in Plasma
Time frame: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose
Median drug levels of tenofovir (TFV), emtricitabine (FTC), and bictegravir (BIC) in plasma were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are plasma concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.
Median Drug Concentration in Peripheral Blood Mononuclear Cells (PBMCs)
Time frame: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose
Median drug concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in PBMCs were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are PBMC concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.
Median Drug Levels in Rectal Tissues
Time frame: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose
Median drug levels of TFV, FTC, and BIC in rectal tissue were determined. Concentrations below the limit of quantification (LOQ) are assigned a value of zero. The prespecified outcomes of interest are rectal tissue concentrations of the components of Biktarvy at 24 and 120 hours after the initial dose. All other time points of sample collection are for future exploratory analyses and have not been analyzed. Only the time points of sample collection that were prespecified as primary study outcomes are presented here.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after de-identification (e.g., text, tables, figures, and appendices), will be available for sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Colleen Kelley, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Biktarvy in people with ART and HIV, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Drug Levels in Plasma (time frame: Baseline (pre-dosing), 24 hours after the first dose, and 120 hours after first dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2022.