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

NCT03976752 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: IRB00108386
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV/AIDS

Keywords

HIV; MSM; Anti-retrovirals; Pharmacokinetics; Peri-exposure HIV prophylaxis

Outcome Measures

Primary Outcomes (3)

• Plasma Concentration of Tenofovir (TFV)

  Median drug concentrations of the TFV component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

  Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

• Plasma Concentration of Emtricitabine (FTC)

  Median drug concentrations of the FTC component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

  Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

• Plasma Concentration of Elvitegravir (EVG)

  Median drug concentrations of the EVG component of Genvoya were determined at baseline and at each of the protocol specified follow-up time points. Concentrations below the limit of quantification (LOQ) are assigned a value of zero.

  Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Secondary Outcomes (2)

• Peripheral Blood Mononuclear Cell (PBMC) Concentration of Tenofovir-diphosphate (TFV-DP)

  Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

• Peripheral Blood Mononuclear Cell (PBMC) Concentration of Emtricitabine-triphosphate (FTC-TP)

  Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

Other Outcomes (5)

• Rectal Tissue Concentration of Tenofovir (TFN)

  Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

• Rectal Tissue Concentration of Emtricitabine (FTC)

  Baseline, and 2, 4, 8, 24, 48, 72, 96 hours after taking the second dose of medication

• Rectal Tissue Concentration of Elvitegravir (EVG)

  Baseline, and 2, 4, 8, 24, 72, 96 hours after taking the second dose of medication

Study Arms (5)

Pre-drug

NO INTERVENTION

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.

Genvoya - 2 and 48 hours specimen collection

EXPERIMENTAL

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 - 4 and 72 hours specimen collection

EXPERIMENTAL

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 - 24 and 96 hours specimen collection

EXPERIMENTAL

Specimen collection 24 hours after taking the medication in the clinic (visit 4), and 96 hours after taking the medication in the clinic (visit 5).

Drug: Genvoya

Genvoya - Single time point specimen collection

EXPERIMENTAL

Specimen collection 8 hours after taking the medication in the clinic (visit 4).

Drug: Genvoya

Interventions

Genvoya DRUG

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 24 hours after home dosing, participants will be given another single dose of Genvoya at the clinic.

Also known as: Cobicistat/Elvitegravir/Emtricitabine/Tenofovir alafenamide

Genvoya - 2 and 48 hours specimen collection; Genvoya - 24 and 96 hours specimen collection; Genvoya - 4 and 72 hours specimen collection; Genvoya - Single time point specimen collection

Eligibility Criteria

• Age: 18 Years - 49 Years
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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, or vaginal perforation, 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

Sponsors & Collaborators

• Emory University: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Hope Clinic

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Cobicistat

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Colleen Kelley
• Organization: Emory University

colleen.kelley@emory.edu

404-712-1823

Study Officials

• Colleen Kelley, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 4, 2019
• First Posted: June 6, 2019
• Study Start: March 13, 2019
• Primary Completion: September 20, 2019
• Study Completion: September 20, 2019
• Last Updated: August 13, 2021
• Results First Posted: August 13, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

US (1)