PREVENT CLINICAL STUDY
The PREVENT Phase I Clinical Study
The PREVENT clinical study at the core of this Program is the first clinical trial of the proprietary lectin Q-GRFT as an HIV microbicide. The upcoming PREVENT trial will be a prospective, randomized, placebo-controlled, Phase I clinical trial of a Q-GRFT-containing solution, administered rectally to men and women participants. The study will be conducted at the University of Pittsburgh Medical Center.
Plant-produced Q-GRFT is one of the most potent, broad-spectrum HIV entry inhibitors yet described, with picomolar activity against HIV-1 (strains from all major clades), HIV-2, HSV, and HCV. We have shown that various formulations of the active pharmaceutical ingredient (API) have outstanding preclinical safety profiles. Addressing immunotoxicity is an important goal for microbicide clinical trials, and particularly so for potentially antigenic protein APIs such as Q-GRFT. Our study will investigate whether Q-GRFT exposure increases the numbers of HIV target cells in the rectal mucosa. We will also analyze the global impact of Q-GRFT treatment on the mucosal environment in the rectum following exposure to Q-GRFT focusing on changes in transcriptomic, proteomic, and microbiome profiles. Given an increasing awareness of the link between microbiome dynamics and host health, these studies will provide a novel dimension to the package of preclinical safety data that we intend to collect.
Participants in the PREVENT study will be enrolled in 3 cohorts or study arms: Arm 1 (n=3) will receive Q-GRFT enema open-label, and Arm 2 (n=12) and Arm 3 (n=6) will receive, respectively, Q-GRFT or placebo enema in a randomized, blinded fashion. As shown in the study diagram below, the study will have two separate stages with all product administered directly by a study clinician.
Participants in the PREVENT study will be screened to exclude those with HIV infection, and anorectal sexually transmitted infections (STIs) (Visit 1). Up to 28 days after screening, eligible participants will return for a baseline visit (Visit 2), be assigned to a study arm, and undergo sample collection.
The first 3 participants will be assigned to Arm 1 and receive a clinician administered single dose exposure of open-label Q-GRFT. The remaining 18 participants will be assigned 2:1 in a randomized and blinded fashion to either Study Arm 2 or 3, respectively.
At Visit 3, participants will receive a clinician-administered single-dose exposure followed by tissue collection at 1-hr and PK sampling at 1-hr and 4-hr. Participants will return to clinic the next day (Visit 4) for 24-hr tissue and PK sampling. Participants in Arm 1 will return for additional tissue and PK sampling at 48 hrs (Visit 4a) following Visit 3.
Once the participants in Arm 1 complete Visit 4, study activity will be paused while the study Protocol Safety Review Team (PSRT) conducts an interim review of the clinical and laboratory data. In the absence of any significant safety concerns, the PSRT will be asked to approve enrollment of Study Arms 2 and 3. Participants will be contacted by study staff approximately 3 days after Visit 4 to collect safety information. Participants will return for a final study visit, Visit 5, 4 weeks +/- 1 week after Visit 4/4a to collect blood samples for PK and immunogenicity assessments. A final study exit call for safety will occur within one week after the final study visit.
Additional subjects in Arm 1 (open label, non-randomized) will be enrolled at the discretion of the Principal Investigator until complete data is obtained on three subjects to account for research participants who are enrolled but exit the study prior to completion. There will be no additional enrollment of subjects in Arms 2 and 3.
Samples collected in this clinical study will be used to assess product efficacy by challenging the tissues with HIV-1 ex vivo. Thus, we will derive PD data by: (1) assessing antiviral activity of rectal fluids collected throughout the study; and (2) challenging tissue explants with virus to qualify the efficacy of the product in the context of any immune response that might have developed during exposure.