Body Compartment PK for New HIV Pre-exposure Prophylaxis Modalities

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02985996

Enrollment

Registered

2016-12-07

Start date

2017-02-06

Completion date

2017-11-29

Last updated

2019-09-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections

Keywords

Preventative Medicine, Infectious Diseases, Sexually Transmitted Diseases

Brief summary

The purpose of this study is to determine the ability of new anti-HIV agents to penetrate different body compartments in HIV negative men who have sex with men and transgender women. These new agents might be considered for pre-exposure prophylaxis regimens in the future. This study will include 90 healthy, HIV-negative men who have sex with men and transgender women who are not taking hormones aged 18-49 years. Participant must be willing to participate in 1 of the 3 study phases, be willing to take Truvada® (PrEP) or Genvoya®, and willing to undergo blood draws, urethral swabs, and rectal biopsy procedures.

Detailed description

Men who have sex with men (MSM) and Transgender women (TGW) who have sex with men continue to be disproportionately affected by HIV. Over 60% of new HIV infections in the US occur among MSM. The majority of HIV infections among MSM and TGW occur through exposure to the rectal mucosa during receptive anal intercourse (RAI). Pre-exposure prophylaxis (PrEP) is a new HIV prevention method that is recommended by CDC and WHO for MSM at risk of HIV infection. PrEP entails taking an anti-HIV medication (Truvada®; tenofovir/emtricitabine) on a daily basis to prevent HIV infection. However, current tenofovir- based regimens have shown to have side effects that researchers are hoping to reduce in newly developed anti-HIV agents. This study is designed to examine the ability of these new agents to penetrate mucosal tissues and potentially prevent HIV infection during RAI exposure for MSM and TGW.

Interventions

DRUGTruvada

Truvada is intended for the treatment of HIV-1 infection. Truvada is a combination of emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in one tablet.

DRUGGenvoya

Genvoya is a 1-pill, once-a-day prescription medicine used to treat HIV-1. Genvoya is a combination of 150 mg of elvitegravir, 150 mg of cobicistat, 200 mg of emtricitabine, and 10 mg of tenofovir alafenamid in one tablet.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to 49 Years

Healthy volunteers

Inclusion criteria

* HIV-negative man who reports receptive anal sex with another man in the last 6 months * Male to female transgender women who have sex with men who report receptive anal intercourse with another man in the last 6 months and are not currently taking hormonal therapy or plan to take hormonal therapy for the duration of the study * Not currently taking PrEP and no plans to initiate during study * Able to provide informed consent in English * No plans for relocation in the next 3 months * Willing to undergo peripheral blood 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.

Exclusion criteria

* 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 * 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 * 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 or vaginal 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: 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 products lubricants or douching used for sexual intercourse * 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 * Intent to use HIV antiretroviral pre-exposure prophylaxis (PrEP) 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.

Design outcomes

Primary

Measure	Time frame	Description
Changes in Intracellular Emtricitabine Triphosphate (FTC-TP)	Baseline, Visit 4 (Up to ten days post drug)	Intracellular emtricitabine triphosphate (FTC-TP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Changes in Intracellular Tenofovir Diphosphate (TFV-DP)	Baseline, Visit 4 (Up to ten days post drug)	Intracellular tenofovir diphosphate (TFV-DP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Secondary

Measure	Time frame	Description
Change in Plasma Tenofovir Alafenamide (TAF) Concentration	Baseline, Visit 4 (Up to ten days post drug)	Plasma tenofovir alafenamide (TAF) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Plasma Elvitegravir (EVG) Concentration	Baseline, Visit 4 (Up to ten days post drug)	Plasma elvitegravir (EVG) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Rectal Emtricitabine (FTC) Concentration	Baseline, Visit 4 (Up to ten days post drug)	Emtricitabine (FTC) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Rectal Tenofovir Disoproxil Fumarate (TDF) Concentration	Baseline, Visit 4 (Up to ten days post drug)	Tenofovir disoproxil fumarate (TDF), concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Rectal Tenofovir Alafenamide (TAF) Concentration	Baseline, Visit 4 (Up to ten days post drug)	Tenofovir alafenamide (TAF) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Rectal Elvitegravir (EVG) Concentration	Baseline, Visit 4 (Up to ten days post drug)	Elvitegravir (EVG) concentration is measured from rectal secretion specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Elvitegravir (EVG) Concentration in Penile Secretions	Baseline, Visit 4 (Up to ten days post drug)	Elvitegravir (EVG) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Intracellular Tenofovir Alafenamide (TAF) Concentration in Peripheral Blood Mononuclear Cells (PBMCs)	Baseline, Visit 4 (Up to ten days post drug)	Intracellular tenofovir alafenamide (TAF) concentration is measured from isolated PBMCs collected via blood draw. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Plasma Emtricitabine (FTC) Concentration	Baseline, Visit 4 (Up to ten days post drug)	Plasma emtricitabine (FTC) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Intracellular Emtricitabine (FTC) Concentration in Rectal Tissue	Baseline, Visit 4 (Up to ten days post drug)	Tissue emtricitabine (FTC) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Intracellular Tenofovir (TFV) Concentration in Rectal Tissue	Baseline, Visit 4 (Up to ten days post drug)	Intracellular tenofovir (TFV) Concentration in Rectal Tissue is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Tenofovir Alafenamide (TAF) Concentration in Rectal Tissue	Baseline, Visit 4 (Up to ten days post drug)	Tissue tenofovir alafenamide (TAF) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Elvitegravir (EVG) Concentration in Rectal Tissue	Baseline, Visit 4 (Up to ten days post drug)	Tissue elvitegravir (EVG) concentration is measured from rectal biopsies and isolated cells. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Emtricitabine (FTC) Concentration in Penile Secretions	Baseline, Visit 4 (Up to ten days post drug)	Emtricitabine (FTC) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Tenofovir Disoproxil Fumarate (TDF) Concentration in Penile Secretions	Baseline, Visit 4 (Up to ten days post drug)	Tenofovir disoproxil fumarate (TDF) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Tenofovir Alafenamide (TAF) Concentration in Penile Secretions	Baseline, Visit 4 (Up to ten days post drug)	Tenofovir alafenamide (TAF) concentrations is measured from urethral and penile specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
PrEP Efficacy as Measured by Inhibition of in Vitro Infection of Rectal Biopsies to HIV	Up to 10 months post-baseline	Rectal biopsies will be subjected to in vitro infection with HIV to test for changes in susceptibility to virus infection. Concentrations of cumulative p24 production in supernatants following in vitro infection of rectal biopsies correlate with viral infection and replication in rectal biopsies. Therefore, lower concentrations of p24 production in biopsies collected from men receiving PrEP compared to controls indicates a potential greater protection from infection and potential increased PrEP efficacy. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Intracellular Elvitegravir (EVG) Concentration in Peripheral Blood Mononuclear Cells (PBMCs)	Baseline, Visit 4 (Up to ten days post drug)	Intracellular elvitegravir (EVG) concentration is measured from isolated PBMCs collected via blood draw. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.
Change in Plasma Tenofovir Disoproxil Fumarate (TDF) Concentration	Baseline, Visit 4 (Up to ten days post drug)	Plasma tenofovir disoproxil fumarate (TDF) concentration is measured from blood specimen. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.

Countries

United States

Participant flow

Pre-assignment details

24 participants were recruited in Phase II, but only 18 were randomized to either Genvoya or Truvada due to lost to follow up. 19 participants were recruited in Phase III, but only 16 were randomized to either Genvoya or Truvada due to lost to follow up.

Participants by arm

Arm	Count
Phase I/Pre-Drug Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	5
Phase II/Genvoya Participants will receive one dose Genvoya. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	8
Phase II/Truvada Experimental: Phase II/Truvada Participants will receive one dose of Truvada. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	10
Phase III/Genvoya Participants will receive Genvoya once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	7
Phase III/Truvada Participants will receive Truvada once daily for ten days. Participants will be asked to provide blood and urine samples and undergo penile, urethral, and rectal swabs. Up to 12 rectal biopsies will be taken.	9
Total	39

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Protocol Violation	0	1	0	0	0
Overall Study	Withdrawal by Subject	0	0	1	0	0

Baseline characteristics

Characteristic	Phase III/Truvada	Phase I/Pre-Drug	Phase II/Genvoya	Phase II/Truvada	Phase III/Genvoya	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	9 Participants	5 Participants	8 Participants	10 Participants	7 Participants	39 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	4 Participants	2 Participants	3 Participants	7 Participants	6 Participants	22 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Race (NIH/OMB) White	4 Participants	3 Participants	5 Participants	2 Participants	1 Participants	15 Participants
Region of Enrollment United States	9 participants	5 participants	8 participants	10 participants	7 participants	39 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	9 Participants	5 Participants	8 Participants	10 Participants	7 Participants	39 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 8	0 / 10	0 / 7	0 / 9
other Total, other adverse events	0 / 5	0 / 8	0 / 10	0 / 7	0 / 9
serious Total, serious adverse events	0 / 5	0 / 8	0 / 10	0 / 7	0 / 9

Outcome results

Primary

Changes in Intracellular Emtricitabine Triphosphate (FTC-TP)

Intracellular emtricitabine triphosphate (FTC-TP) is measured and compared from blood specimen in both arms from baseline to visit 4. For the pharmacokinetic analysis, values reported as Below the Limit of Quantification (BLOQ) are assigned a value of zero if it occurs in a profile after dosing at time zero and before the first measurable concentration.