Evaluating the Safety and Pharmacokinetics of PC-1005 Administered Rectally to HIV-1 Seronegative Adults

NCT03408899 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MTN-03735122
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and pharmacokinetics of PC-1005 gel when used as a rectal microbicide in HIV-uninfected men and women (cis or transgender) with a history of consensual receptive anal intercourse.

Conditions

HIV Infections

Keywords

Microbicides

Outcome Measures

Primary Outcomes (4)

• Frequency of Grade 2 or Higher Adverse Events (AEs)

  AEs are defined by the Division of AIDS Table for Grading the Severity of 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 through participants' last study visit which will occur at Month 3 to 5, depending on the participant

• MIV-150 Concentrations in Plasma

  Descriptive statistics such as the mean and median and corresponding 95% confidence intervals will be used to describe the MIV-150 concentrations in all biological matrices assessed at all scheduled time points

  Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant

• MIV-150 Concentrations in Rectal Fluid

  Descriptive statistics such as the mean and median and corresponding 95% confidence intervals will be used to describe the MIV-150 concentrations in all biological matrices assessed at all scheduled time points

  Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant

• MIV-150 Concentrations in Rectal Mucosal Tissue Homogenates

  Descriptive statistics such as the mean and median and corresponding 95% confidence intervals will be used to describe the MIV-150 concentrations in all biological matrices assessed at all scheduled time points

  Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant

Secondary Outcomes (5)

• Participant Self-report Gel Acceptability - Ease of Use

  Through study completion, approximately 3-5 months for each participant

• Participant Self-report Gel Acceptability - Feeling When Inserted

  Through study completion, approximately 3-5 months for each participant

• Participant Self-report Gel Acceptability - Problems With Gel Use

  Through study completion, approximately 3-5 months for each participant

• Participant Self-report Gel Acceptability - Gel Acceptability

  Through study completion, approximately 3-5 months for each participant

• MIV-150 Concentrations in Vaginal Fluid

  Measured through participants' last study visit which will occur at Month 3 to 5, depending on the participant

Study Arms (1)

PC-1005

EXPERIMENTAL

All participants will receive 3 single escalating doses of PC-1005 gel during Visits 3, 5, and 7, with a 2-to-6-week washout period between dosing visits. Each participant will be on study for approximately 3 to 5 months.

Drug: PC-1005 gel

Interventions

PC-1005 gel DRUG

PC-1005 (0.002% MIV-150/0.3% zinc acetate in 3.0% carrageenan gel) in 4 mL, 16 mL, and 32 mL doses administered rectally.

PC-1005

Eligibility Criteria

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

You may qualify if:

• Men and women (cis or transgender) who are 18 years or older at Screening, verified per site standard operating procedure (SOP)
• Able and willing to provide written informed consent
• HIV-1/2 uninfected at Screening and Enrollment, per applicable algorithm in the protocol and willing to receive HIV test results
• Able and willing to provide adequate locator information, as defined in site SOP
• Available to return for all study visits and willing to comply with study participation 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 their lifetime per participant report
• Willing to not 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 follow abstinence requirements for the duration of study participation (See the protocol for additional information)
• 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 and intending to use an effective method for the duration of study participation; these include:
• Hormonal methods, excluding vaginal rings
• Intrauterine device (IUD) inserted at least 42 days prior to Enrollment (but not past the maximum length of recommended usage according to package instructions)
• Sterilization of participant or partner at least 42 days prior to Enrollment
• Self-identifies as having sex with women exclusively

You may not qualify if:

• At Screening:
• Hemoglobin Grade 1 or higher\*
• Platelet count Grade 1 or higher\*
• White blood count Grade 2 or higher\*
• Aspartate aminotransferase (AST) or alanine transaminase (ALT) Grade 1 or higher\*
• Serum creatinine greater than 1.3x the site laboratory upper limit of normal (ULN)
• International normalized ratio (INR) greater than 1.5x the site laboratory ULN
• History of inflammatory bowel disease by participant report
• \* As per the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1, July 2017
• Known adverse reaction to latex or polyurethane (ever)
• Anticipated use of and/or unwillingness to abstain from the following medications during study participation:
• Anticoagulant medications
• Rectally-administered medications
• Known adverse reaction to any of the components of the study product
• Use of pre-exposure prophylaxis (PrEP) for HIV prevention within 1 month prior to Enrollment, and/or anticipated use and/or unwillingness to abstain from PrEP during trial participation

Sponsors & Collaborators

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

Study Sites (2)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Ho K, Hoesley C, Anderson PL, Fernandez-Romero JA, Friedland BA, Kelly CW, Jiao Y, Edick S, Brand R, Kunjara Na Ayudhya RP, Zyhowski A, Hartman DJ, Reddy NB, Al-Khouja A, Piper J, Bauermeister JA, Teleshova N, Melo C, Cornejal N, Barnable P, Singh D, Scheckter R, McClure T, Hillier SL, Hendrix CW; MTN-037 Study Team. Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037). J Acquir Immune Defic Syndr. 2024 Dec 1;97(4):379-386. doi: 10.1097/QAI.0000000000003506.

  PMID: 39808074 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: Craig Hendrix, MD
• Organization: Johns Hopkins University

chendrix@jhmi.edu

4109559707

Study Officials

• Craig Hendrix, MD

  Johns Hopkins University

  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: January 18, 2018
• First Posted: January 24, 2018
• Study Start: June 19, 2018
• Primary Completion: April 19, 2019
• Study Completion: April 19, 2019
• Last Updated: April 14, 2023
• Results First Posted: April 14, 2023

Record last verified: 2023-04

Locations

US (2)