Griffithsin-based Rectal Microbicide for PREvention of Viral ENTry (PREVENT)

NCT04032717 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY19030322U19AI113182
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is the first-in-human clinical study to see if a single dose of an investigational enema made from a modified plant protein called Q-Griffithsin is safe, tolerated, and acceptable for use by healthy adults 18-45 years of age who practice receptive anal intercourse.

Conditions

HIV Prevention

Keywords

microbicide; enema; receptive anal intercourse; HIV prevention; HIV transmission

Outcome Measures

Primary Outcomes (7)

• The number and frequency of adverse events Grade 2 or higher and genitourinary adverse events Grade 1 or higher

  Safety analysis will be conducted on all participants who have receive study product. The number and the frequency of ≥ Grade 2 adverse events (AEs) and ≥ Grade 1 Genitourinary AEs as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric AEs, Version 2.1 (March 2017), Addendum 1 Female Genital Grading Table for Use in Microbicide Studies (November 2007), and/or Addendum 3 Rectal Grading Table for Use in Microbicide Studies (Clarification dated May 2012) to this table will be tabulated for each of the three methods of administration from Baseline through the final study contact. To determine whether AEs are occurring excessively, the proportion of subjects that experience an AE will be calculated for each method of administration. Additional safety analyses will also tabulate the number and type of AEs observed overall, and by severity, site, and study product. AEs that lead to discontinuation of study participation will be tabulated separately.

  Baseline through the final study contact, or about 8 weeks

• The proportion of participants who report product characteristics to be considered a barrier in study product use, operationalized as having a rating of lower than 3 on a 5-point Likert scale, in disliking or likelihood of future use

  One day after study product administration, participants will complete an acceptability questionnaire to provide descriptive statistics on participants' opinions on the enema's characteristics, application process, the applicator design and the use-regimen, as well as the degree to which participants believe these characteristics and side-effects could pose barriers in future sustained use. On a 5-point Likert scale, with 1 being completely unacceptable and 5 being highly acceptable, the distributions of scores on all product characteristics will be examined to determine product characteristics that pose or could pose significant barriers in current or future product use.

  Once 24 hours post-dose

• Area under the concentration-time curve (AUC) of Q-GRFT

  AUC of Q-GRFT as measured in plasma, rectal fluid, rectal mucosal tissue homogenates, and enema fluid effluent.

  Pre-dose and 1, 4, and 24 hours post-dose

• Maximum concentration (Cmax) of Q-GRFT

  Cmax of Q-GRFT as measured in plasma, rectal fluid, rectal mucosal tissue homogenates, and enema fluid effluent.

  Pre-dose and 1, 4, and 24 hours post-dose

• Time to maximum concentration (Tmax) of Q-GRFT

  Tmax of Q-GRFT as measured in plasma, rectal fluid, rectal mucosal tissue homogenates, and enema fluid effluent .

  Pre-dose and 1, 4, and 24 hours post-dose

• Minimum concentration (Cmin) of Q-GRFT

  Cmin of Q-GRFT as measured in plasma, rectal fluid, rectal mucosal tissue homogenates, and enema fluid effluent.

  Pre-dose and 1, 4, and 24 hours post-dose

• Half-life (t½) of Q-GRFT

  t½ of Q-GRFT as measured in plasma, rectal fluid, rectal mucosal tissue homogenates, and enema fluid effluent.

  Pre-dose and 1, 4, and 24 hours post-dose

Secondary Outcomes (1)

• Change in humoral antibody responses to Q-GRFT in blood by ELISA and PBMC Q-GRFT antigen stimulation

  Baseline and 4 weeks post-dose

Study Arms (3)

Open-label Q-GRFT enema

EXPERIMENTAL

Open-label Q-GRFT enema administered rectally once as a single dose (Arm 1)

Drug: Q-Griffithsin (Q-GRFT) enema

Randomized, blinded Q-GRFT enema

EXPERIMENTAL

Blinded Q-GRFT enema administered rectally once as a single dose (Arm 2)

Drug: Q-Griffithsin (Q-GRFT) enema

Randomized, blinded placebo enema

PLACEBO COMPARATOR

Blinded placebo enema administered once as a single dose (Arm 3)

Other: Placebo enema

Interventions

Q-Griffithsin (Q-GRFT) enema DRUG

Investigational enema composed of 4.2mL Q-Griffithsin (Q-GRFT) 9.6mg/mL combined with approximately 120.8mL of 0.9% sodium chloride solution to yield an active enema study product that will contain and deliver a dose of approximately 40mg of Q-GRFT

Also known as: Study product enema

Open-label Q-GRFT enema; Randomized, blinded Q-GRFT enema

Placebo enema OTHER

Approximately 125mL of 0.9% sodium chloride solution

Randomized, blinded placebo enema

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: This study will exclude transgender populations. Although it is recognized that this is a critical group to include in the evaluation of new HIV prevention products it is felt that inclusion of transgender populations would increase the heterogeneity of the study population and it is not clear what the impact of exogenous hormones might be on immunological or pharmacokinetic parameters being evaluated in the study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age of 18 through 45 years at screening, verified per site SOP
• Male participants, born male; female participants, born female.
• Availability to return for all study visits, barring unforeseen circumstances
• Willing and able to
• communicate in English
• provide written informed consent to take part in the study
• provide adequate locator information, as defined in site SOP
• Must agree
• not to participate in other concurrent interventional and/or drug trials
• to use study-provided condoms for vaginal or anal intercourse for the duration of the study
• to avoid insertion of anything in the vagina or rectum (e.g., penis, sex toy, medication, enemas) 72 hours before and after study product exposure and rectal sampling visits
• Understands and agrees to local STI reporting requirements
• HIV-1 seronegative at screening and enrollment
• A history of RAI at least 5 times in lifetime and once in the prior year. (Required to assure that participants are comfortable with study procedures and study product administration.)
• Must be in general good health in the opinion of the investigator

You may not qualify if:

• Undergoing or completed gender reassignment
• Participant reports any of the following at Screening:
• Post-exposure prophylaxis for HIV exposure within 4 weeks prior to screening
• Condomless insertive or receptive anal intercourse with more than one partner in the past six months
• Known HIV-positive sexual partner within the last 6 months
• History of STI in the last 3 months
• Transactional sex within the last 12 months
• Non-therapeutic injection drug use in the 12 months prior to screening
• Any use of methamphetamine, gamma hydroxybutyrate, cocaine or heroin in the 12 months prior to screening
• History of recurrent urticaria
• Use of antiretroviral medications with activity against HIV within the 4 weeks prior to the Enrollment, including PrEP with Truvada®
• Use of systemic immunomodulatory medications within the 4 weeks prior to the Enrollment
• Use of rectally administered medications or products (including condoms) containing Nonoxynol-9 (N-9) within the 4 weeks prior to the Enrollment
• Participating in another research study involving drugs or medical devices within the 4 weeks prior to the Enrollment
• Has plans to relocate away from the study site area during the period of study participation

Sponsors & Collaborators

• Rhonda Brand: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Intrucept Biomedicine LLC: collaborator

Study Sites (1)

HIV/AIDS Clinical Research Unit / University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Shrivastava-Ranjan P, Lo MK, Chatterjee P, Flint M, Nichol ST, Montgomery JM, O'Keefe BR, Spiropoulou CF. Hantavirus Infection Is Inhibited by Griffithsin in Cell Culture. Front Cell Infect Microbiol. 2020 Nov 4;10:561502. doi: 10.3389/fcimb.2020.561502. eCollection 2020.

  PMID: 33251157 DERIVED

MeSH Terms

Interventions

q-griffithsin; Enema

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• Ken Ho, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Arm 1 will enroll 3 participants to receive the open-label Q-GRFT enema. The remaining 18 participants will be randomized 2:1 (Q-GRFT enema: placebo enema) resulting in twelve participants enrolled into Arm 2 and six participants enrolled into Arm 3. The randomization scheme will be generated by the statistical group.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: randomized, double-blind

Study Record Dates

• First Submitted: April 2, 2019
• First Posted: July 25, 2019
• Study Start: July 10, 2019
• Primary Completion: February 4, 2021
• Study Completion: February 4, 2021
• Last Updated: July 6, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Upon publication

Locations

US (1)