NCT06798454

Single Ascending Dose Study to Evaluate Safety Tolerability, Pharmacokinetics, and Pharmacodynamics of PVT201 in Healthy Subjects and Patients (PBC/PSC)

A Phase 1, First-In-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PVT201 Following Randomized, Double-blind, Placebo-controlled Single Ascending Doses in Healthy Subjects and Patients (PBC/PSC)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (actual)
• Sponsor: Parvus Therapeutics, Inc. · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The goal of this clinical trial is to learn what happens to PVT201 when it enters your body and how it affects your immune system. It will also learn about the safety of PVT201 after a single dose. The main questions it aims to answer are: Will participants experience any side effects when taking PVT201? How long does it take PVT201 to leave your body after you take it? Healthy volunteers will: stay in the clinic for two nights, get one dose of PVT201 or a placebo intravenously (through a vein) on Day 1, have blood drawn periodically throughout their stay and be monitored for side effects, and return to the clinic approximately one week after their dose for a final study visit. Patients with primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) will have the same procedures performed as healthy volunteers; however, none of the patients will receive placebo (all patients will be given PVT201).

Detailed description

This is a randomized, double-blind, placebo-controlled, single ascending dose, multi-cohort study conducted in healthy participants and patients with PBC/PSC. Healthy adult participants will be enrolled to 1 of 4 main cohorts (Cohorts 1-4; 6 participants per cohort), and randomized to receive single ascending doses of PVT201 or placebo. Dosing in each cohort begins with two sentinel subjects randomized such that one will receive PVT201 and the other will receive placebo (normal saline; 0.9% sodium chloride). The safety and tolerability of each sentinel participant will be monitored in the clinic until 24 hours post-dose. Following completion of Day 2 assessments for sentinel participants, all available safety/tolerability information will be reviewed prior to making the decision to dose the remaining participants in each cohort. Participants will be discharged after Day 2 assessments have been completed, and will return to the clinic for a final study visit on Day 7. After the completion of each cohort, the decision to advance to the next dose cohort will be made by the Safety Review Committee (SRC) following review of safety and tolerability data of at least 4 of 6 participants, up to and including the Day 7 visit. Cohorts will be dosed in an escalating order, unless otherwise indicated by the Safety Review Committee. At the discretion of the Sponsor and Safety Review Committee, healthy adult participants may be enrolled in up to one additional cohorts (6 participants per cohort) and randomized to receive single doses of PVT201 or placebo (ratio 2:1 active:placebo), to achieve the objectives of the study. If an additional cohort is required, it will commence with two sentinels, with one of the two sentinels randomized to receive PVT201 and the other randomized to receive placebo. After completion of a minimum of 4 cohorts and with the approval of the SRC, the final cohort of the study will enroll up to 6 patients diagnosed with either PBC or PSC (of which at least half of the participants must have PBC). This cohort will not be blinded or placebo controlled, but will commence with one sentinel subject that will be monitored as noted above for previous cohorts prior to subsequent subject dosing. The dose level of the cohort will be the highest dose administered in the previous cohorts that was deemed safe and well tolerated by the SRC. All study visits and procedures noted for the healthy volunteer cohorts will also apply to the PBC/PSC patient cohort.

Conditions

• Primary Biliary Cholangitis (PBC)

Interventions

Type	Name	Description
DRUG	PVT201	Navacims are a novel class of nano-particle-based therapeutics being developed for the treatment of autoimmune diseases. A navacim consists of an iron oxide core surrounded by dextran that has been linked to multiple copies of a major histocompatibility complex Class II molecule and peptide. The peptide representing a disease-associated autoantigen and its paired MHC II molecule are specific to each autoimmune disease, and will be recognized by the T-cell antigen receptor. PVT201 is a navacim that will be used to target human PDC-reactive effector T-cells in patients with primary biliary cholangitis (PBC), converting them to Type 1 regulatory cells. IV delivery of navacims in nonclinical models of PBC induced immune tolerance and attenuation of disease pathology without impairing normal immunity to vaccines or viral and bacterial infections. PVT201 will be administered intravenously.
OTHER	Placebo	Participants randomized to placebo will be administered normal saline IV.

Timeline

• Start date: 2024-10-15
• Primary completion: 2025-04-23
• Completion: 2025-04-23
• First posted: 2025-01-29
• Last updated: 2025-11-24

Locations

1 site across 1 country: Australia