Body Compartment PK for New HIV Pre-exposure Prophylaxis Modalities

NCT02985996 | Completed Phase 1 Results FDA Drug

• 1 other identifier: IRB00092488
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections

Keywords

Preventative Medicine; Infectious Diseases; Sexually Transmitted Diseases

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline, Visit 4 (Up to ten days post drug)

• Changes in Intracellular Tenofovir Diphosphate (TFV-DP)

  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.

  Baseline, Visit 4 (Up to ten days post drug)

Secondary Outcomes (19)

• Change in Plasma Emtricitabine (FTC) Concentration

  Baseline, Visit 4 (Up to ten days post drug)

• Change in Plasma Tenofovir Disoproxil Fumarate (TDF) Concentration

  Baseline, Visit 4 (Up to ten days post drug)

• Change in Plasma Tenofovir Alafenamide (TAF) Concentration

  Baseline, Visit 4 (Up to ten days post drug)

• Change in Plasma Elvitegravir (EVG) Concentration

  Baseline, Visit 4 (Up to ten days post drug)

• Change in Rectal Emtricitabine (FTC) Concentration

  Baseline, Visit 4 (Up to ten days post drug)

Study Arms (5)

Phase I/Pre-Drug

NO INTERVENTION

Ten participants will be asked to complete study phase 1. 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.

Phase II/Genvoya

EXPERIMENTAL

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.

Drug: Genvoya

Phase II/Truvada

EXPERIMENTAL

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.

Drug: Truvada

Phase III/Genvoya

EXPERIMENTAL

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.

Drug: Genvoya

Phase III/Truvada

EXPERIMENTAL

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.

Drug: Truvada

Interventions

Truvada DRUG

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.

Phase II/Truvada; Phase III/Truvada

Genvoya DRUG

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.

Phase II/Genvoya; Phase III/Genvoya

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: 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
• 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.

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
• Significant laboratory abnormalities at baseline visit, including but not limited to:
• Hgb ≤ 10 g/dL
• PTT \> 1.5x ULN or INR \> 1.5x ULN
• Platelet count \<100,000
• 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:
• 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 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:
• Aspirin or more than 4 doses of NSAIDs
• Warfarin, heparin (low-molecular weight or unfractionated), platelet aggregation inhibitors, or fibrinolytic agents

Sponsors & Collaborators

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

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

HIV Infections; Communicable Diseases; Sexually Transmitted Diseases

Interventions

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

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Infections; Sexually Transmitted Diseases, Viral; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

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

colleen.kelley@emory.edu

404-712-1823

Study Officials

• Colleen Kelley, MD, MPH

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 5, 2016
• First Posted: December 7, 2016
• Study Start: February 6, 2017
• Primary Completion: November 29, 2017
• Study Completion: November 29, 2017
• Last Updated: September 17, 2019
• Results First Posted: September 17, 2019

Record last verified: 2019-08

Locations

US (1)