Safety and Pharmacokinetic Study of Tenofovir Alafenamide (TAF)/Elvitegravir (EVG) Administered Rectally

NCT04047420 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MTN-03938470
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and pharmacokinetics of rectal administration of a tenofovir alafenamide (TAF)/elvitegravir (EVG) insert at two dose levels in HIV-uninfected individuals.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (11)

• Number of Participants With Grade 2 and Higher Adverse Events (AEs)

  Graded per the Division of AIDS (DAIDS) Table for Grading Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 and/or Addenda 1, 2 and 3 (Female Genital \[Dated November 2007\], Male Genital \[Dated November 2007\] and Rectal \[Clarification Dated May 2012\] Grading Tables for Use in Microbicide Studies).

  Measured from Enrollment through Final Contact at Visit 11 with a median (IQR) of 76 (47, 292) days. COVID restrictions delayed first dosing 9-10 months in 5 participants. Follow-up time from first dosing was a median (IQR) of 34 (22, 39) days.

• Elvitegravir (EVG) Concentration in Blood

  Based on laboratory evaluations on samples collected at baseline (pre dose), 1, 2, 4, 6, 24, 48, and 72 hours post dose

  Samples collected at baseline (pre dose), 1, 2, 4, 6, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Elvitegravir (EVG) Concentration in Rectal Fluid

  Based on laboratory evaluations on samples collected at 2, 4, 6, 24, 48, and 72 hours post dose

  Samples collected at 2, 4, 6, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Elvitegravir (EVG) Concentration in Rectal Mucosal Tissue Homogenates

  Based on laboratory evaluations on samples collected at 2, 24, 48, and 72 hours post dose

  Samples collected at 2, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Tenofovir Alafenamide (TAF) Concentration in Blood

  Based on laboratory evaluations on samples collected at baseline (pre dose), 1, 2, 4, 6, 24, 48, and 72 hours post dose

  Samples collected at baseline (pre dose), 1, 2, 4, 6, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Tenofovir Alafenamide (TAF) Concentration in Rectal Fluid

  Based on laboratory evaluations on samples collected at 2, 4, 6, 24, 48, and 72 hours post dose

  Samples collected at 2, 4, 6, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Tenofovir Alafenamide (TAF) Concentration in Rectal Mucosal Tissue Homogenates

  Based on laboratory evaluations on samples collected at 2, 24, 48, and 72 hours post dose

  Samples collected at 2, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Tenofovir (TFV) Concentration in Blood

  Based on laboratory evaluations on samples collected at baseline (pre dose), 1, 2, 4, 6, 24, 48, and 72 hours post dose

  Samples collected at baseline (pre dose), 1, 2, 4, 6, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Tenofovir (TFV) Concentration in Rectal Fluid

  Based on laboratory evaluations on samples collected at 2, 4, 6, 24, 48, and 72 hours post dose

  Samples collected at 2, 4, 6, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Tenofovir (TFV) Concentration in Rectal Mucosal Tissue Homogenates

  Based on laboratory evaluations on samples collected at 2, 24, 48, and 72 hours post dose

  Samples collected at 2, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

• Tenofovir Diphosphate (TFV-DP) Concentration in Rectal Mucosal Tissue Cell Isolates

  Based on laboratory evaluations on samples collected at 2, 24, 48, and 72 hours post dose

  Samples collected at 2, 24, 48, and 72 hours after each dose (up to 9 weeks after first dose)

Secondary Outcomes (3)

• Participant Self-report Rectal Insert Acceptability - Ease of Use

  24 hours after each dose (Visits 4 and 8) (up to 9 weeks after first dose)

• Participant Self-report Rectal Insert Acceptability - Feeling When Inserted

  24 hours after each dose (Visits 4 and 8) (up to 9 weeks after first dose)

• Participant Self-report Rectal Insert Acceptability - Problems With Rectal Insert

  24 hours after each dose (Visits 4 and 8) (up to 9 weeks after first dose)

Study Arms (1)

Tenofovir Alafenamide (TAF)/Elvitegravir (EVG) Insert

EXPERIMENTAL

On the first dosing visit (Visit 3), participants will receive a single TAF/EVG Insert for rectal administration. On the second dosing visit (Visit 7), after a washout period of at least 7 days, participants will receive two TAF/EVG Inserts for rectal administration. Each participant will be on study for approximately 6-13 weeks.

Drug: TAF/EVG Insert

Interventions

TAF/EVG Insert DRUG

TAF/EVG Insert (20/16 mg) administered rectally by study staff

Tenofovir Alafenamide (TAF)/Elvitegravir (EVG) Insert

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals who are 18 years of age or older at Screening, verified per site standard operating procedure (SOP)
• Able and willing to provide written informed consent to be screened for and enrolled in MTN-039
• HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in the study protocol and willing to receive HIV test results
• Able and willing to provide adequate locator information, as defined in site SOP
• Able to communicate in spoken and written English
• Available for all visits and able and willing to comply with all study procedural requirements
• In general good health at Screening and Enrollment, as determined by the site Investigator of Record (IoR) or designee
• At Screening, history of consensual receptive anal intercourse (RAI) at least once in lifetime per participant report
• Willing not to take part in other research studies involving drugs, medical devices, genital or rectal products, or vaccines for the duration of study participation (including the time between Screening and Enrollment)
• Willing to comply with abstinence and other protocol requirements as outlined in the study protocol
• For participants of childbearing potential: a negative pregnancy test at Screening and Enrollment
• For participants of childbearing potential: Per participant report at Enrollment, using an effective method of contraception for at least 30 days (inclusive) prior to Enrollment and intending to use an effective method for the duration of study participation. Effective methods include:
• Hormonal methods
• Intrauterine device (IUD) inserted at least 30 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions)
• Sterilization (of participant or partner, as defined in site SOPs)

You may not qualify if:

• At Screening:
• Hemoglobin Grade 1 or higher\*
• Platelet count Grade 1 or higher\*
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher\*
• Serum creatinine greater than 1.3 times the site laboratory upper limit of normal (ULN)
• International normalized ratio (INR) greater than 1.5 times the site laboratory ULN
• History of inflammatory bowel disease by participant report
• Positive hepatitis B surface antigen (HBsAg) test result
• \*As per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 2017.
• Anticipated use of and/or unwillingness to abstain from the following medications during study participation:
• Anticoagulant medications
• Non-study rectally-administered medications and any products containing nonoxynol-9 (N-9)
• Known adverse reaction to any of the components of the study product
• Use of approved or other investigational pre-exposure prophylaxis (PrEP) for HIV prevention within 3 months prior to Enrollment, and/or anticipated use and/or unwillingness to abstain from PrEP during trial participation
• Use of post-exposure prophylaxis (PEP) for potential HIV exposure within 6 months prior to Enrollment

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• CONRAD: collaborator

Study Sites (2)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Riddler SA, Kelly CW, Hoesley CJ, Ho KS, Piper JM, Edick S, Heard F, Doncel GF, Johnson S, Anderson PL, Brand RM, Kunjara Na Ayudhya RP, Bauermeister JA, Hillier SL, Hendrix CW. A Phase 1 Clinical Trial to Assess the Safety and Pharmacokinetics of a Tenofovir Alafenamide/Elvitegravir Insert Administered Rectally for HIV Prevention. J Infect Dis. 2024 Sep 23;230(3):696-705. doi: 10.1093/infdis/jiae211.

  PMID: 38655842 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Sharon Riddler, MD, MPH
• Organization: University of Pittsburgh

riddler@pitt.edu

4123831741

Study Officials

• Sharon A. Riddler, MD, MPH

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 6, 2019
• Study Start: December 11, 2019
• Primary Completion: March 3, 2021
• Study Completion: April 7, 2021
• Last Updated: December 22, 2023
• Results First Posted: December 22, 2023

Record last verified: 2023-12

Locations

US (2)