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

NCT06798454 | Completed Phase 1 DMC

• 1 other identifier: PVT201_C1_001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Primary Biliary Cholangitis (PBC)

Keywords

first-in-human; healthy volunteer; single ascending dose; PBC; PSC; randomized

Outcome Measures

Primary Outcomes (12)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs) (including withdrawals due to AEs);

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in vital signs (temperature measured in degrees Celsius)

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in vital signs (heart rate measured in beats per minute)

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in vital signs (blood pressure measured in mmHg)

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in clinical laboratory parameters (hematology)

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in clinical laboratory parameters (serum chemistry including liver function tests).

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in clinical laboratory parameters (coagulation parameters).

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in clinical laboratory parameters (urinalysis).

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: PR Interval (msec)

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QRS Duration (msec)

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QT Interval (msec)

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

• To evaluate the safety and tolerability of a single IV dose of PVT201 in healthy participants and in PBC/PSC patients.

  Safety endpoints include change from baseline in electrocardiogram (ECG) parameters: QTcF (msec)

  To be measured at Baseline, Day 1, Day 2, and Day 7 (~7 days)

Secondary Outcomes (7)

• To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.

  Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7

• To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.

  Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7

• To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.

  Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7

• To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.

  Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7

• To measure the pharmacokinetics (PK) of PVT201 in plasma following a single IV dose in healthy participants and in PBC/PSC patients.

  Day 1: pre-dose and t= 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 12 hr; Day 2 = 24 hr; Day 7

Study Arms (2)

PVT201

EXPERIMENTAL

PVT201 will be administered as a single IV dose. Planned doses are: Cohort 1 Healthy Volunteers: A mg/kg Cohort 2 Healthy Volunteers: B mg/kg Cohort 3 Healthy Volunteers: C mg/kg Cohort 4 Healthy Volunteers: D mg/kg Final Cohort PBC/PSC Patients: the highest dose that was deemed safe and well tolerated in the Healthy Volunteer cohorts

Drug: PVT201

Placebo (normal saline, 0.9% sodium chloride)

PLACEBO COMPARATOR

All Healthy Volunteer cohorts will be administered either PVT201 or placebo in a ratio of 2:1 PVT201:placebo. Patient receiving placebo will be administered an equivalent volume of normal saline as a single IV dose. The PBC/PSC patients in the final cohort will not be administered placebo - all patients in this cohort will receive PVT201.

Other: Placebo

Interventions

PVT201 DRUG

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.

Also known as: Navacim

PVT201

Placebo OTHER

Participants randomized to placebo will be administered normal saline IV.

Also known as: normal saline, 0.9% NaCl

Placebo (normal saline, 0.9% sodium chloride)

Eligibility Criteria

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

You may qualify if:

• Healthy male or female, aged between 18 and 65 years, inclusive at Screening.
• Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, with body weight ≥ 50.0 kg and \< 120.0 kg.
• Carry the HLA DRB4\*0101 or DRB4\*0103 allele.
• Participant is medically healthy (in the opinion of the Investigator), as determined by pre-study medical history and without CS abnormalities.
• Female participants must be of non-child-bearing potential, or, if of child-bearing potential:
• Must have a negative serum pregnancy test at the Screening visit and a negative urine pregnancy test on Day -1.
• Must agree not to donate ova or attempt to become pregnant from the time of signing consent until at least 30 days after the dose of study drug.
• If not exclusively in a same-sex relationship or abstinent as a committed lifestyle, must agree to use adequate contraception established at Screening until at least 30 days after the dose of study drug.
• Male participants must:
• Agree not to donate sperm from the time of signing consent until at least 90 days after the dose of study drug.
• If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception from the time of signing consent until at least 90 days after the dose of study drug.

You may not qualify if:

• Any active infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
• History of hypersensitivity reaction, anaphylaxis or other CS reactions or known allergy to the study drug or its ingredients including but not limited to dextran.
• History of any clinically significant disorder which, in the opinion of the Investigator would make implementation of the protocol or interpretation of study results difficult, or that would put the participant at risk by participating in the study.
• Participant has undergone splenectomy or thymectomy.
• Laboratory results at Screening that indicate inadequate renal function, with estimated creatinine clearance of \< 60 mL/min/1.73m2.
• Liver function test results elevated more than 1.5-fold above the upper limit of normal for GGT, ALP, AST or ALT.
• Total bilirubin \> 1.5-fold above the upper limit of normal.
• Use of any prescription medication within 14 days prior to the dose of study drug and/or over-the-counter medication/vitamins/supplements/herbal/plant-derived medications within 7 days prior to the dose of study drug.
• Concurrent enrollment in another clinical study, or participation in another clinical study within 30 days prior to Screening.
• Positive alcohol breath test at Screening, upon admission to the clinic on Day -1.
• Positive urine drugs of abuse test at Screening, upon admission to the clinic on Day -1.
• Participant has a positive cotinine test upon admission to the clinic on Day -1.
• Participant is breastfeeding/lactating or pregnant, or planning to breastfeed or become pregnant during the study.
• Positive Hepatitis B surface antigen (HBsAg), Hepatitis C (HepC) virus antibody, or human immunodeficiency (HIV) antibody tests.
• Known substance abuse or medical, psychological, or social conditions that in the opinion of the study doctor would make the participant unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Sponsors & Collaborators

• Parvus Therapeutics, Inc.: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (1)

CMAX Clinical Research

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The treatment assignment of the healthy volunteer cohorts to either PVT201 or placebo will be masked (double-blind); however, the final cohort of patients with PBS/PSC will be open label (all PBC/PSC patients will receive PVT201)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2024
• First Posted: January 29, 2025
• Study Start: October 15, 2024
• Primary Completion: April 23, 2025
• Study Completion: April 23, 2025
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

AU (1)