A First in Human Study to Assess Safety, Tolerability, Pharmacokinetics of ABI-4334 in Healthy Subjects

A Phase 1, Blinded, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics of Single and Multiple Ascending Doses of ABI-4334 in Healthy Subjects

This study is designed to assess safety, tolerability, and PK of single ascending doses (SAD) of ABI-4334 in Part A and multiple-ascending doses (MAD) of ABI-4334 in Part B in healthy subjects. Effect of food will also be evaluated in Part A.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: ABI-4334 Tablet; Drug: ABI-4334 Placebo

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • New Zealand Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index (BMI) between 18.0 and 30.0 kg/m2
• In good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
• Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1
• Agreement to comply with protocol-specified contraceptive requirements

Exclusion Criteria:

• Positive results for any of the following serology tests, HBsAg, hepatitis B core antibody (HBcAb IgM), hepatitis C virus antibody (HCV Ab), or HIV-1 or -2 antibody
• History of any illness that, in the opinion of the Investigator, might confound the results of the study, pose an additional risk in administering study drug to the subject, or a condition known to interfere with the absorption/ distribution/elimination of drugs.
• History of any significant drug-related allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, urticaria, or multiple drug allergies
• History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
• Has participated in a clinical study involving administration of either an investigational or a marketed drug within 2 months before Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: SAD Cohorts 1-5 ABI-4334 Tablet; A single dose of ABI-4334 will be administered on Day 1 in dose-escalation cohorts with a starting dose of 30 mg. The doses for subsequent cohorts will be determined by evaluation of safety and PK data from previous cohorts.	Drug: ABI-4334 Tablet; ABI-4334 Tablet
Placebo Comparator: Part A: SAD Cohorts 1-5 ABI-4334 Placebo Tablet; A single dose of placebo matching ABI-4334 will be administered on Day 1.	Drug: ABI-4334 Placebo; Placebo to ABI-4334 Tablet
Experimental: Part A: SAD Fed Cohorts 6-7 ABI-4334 Tablet; A single dose of ABI-4334 will be administered after a high-fat meal on Day 1 in cohort 6. A single dose of ABI-4334 will be administered on two separate occasions, once fasted and once after a high-fat meal in cohort 7. The dose administered will be determined after evaluation of cumulative safety and PK data from cohorts 1-5.	Drug: ABI-4334 Tablet; ABI-4334 Tablet
Placebo Comparator: Part A: SAD Fed Cohorts 6 ABI-4334 Placebo Tablet; A single dose of placebo matching ABI-4334 will be administered on Day 1 after a high-fat meal on Day 1 in cohort 6.	Drug: ABI-4334 Placebo; Placebo to ABI-4334 Tablet
Experimental: Part B: MAD Cohorts 1-2 ABI-4334 Tablet; Once-daily doses of ABI-4334 will be administered from Day 1 to Day 8. Cohort B1 will receive a dose determined from evaluation of the data from the SAD cohorts. The doses for the subsequent cohort will be determined by evaluation of safety and PK data from previous cohorts.	Drug: ABI-4334 Tablet; ABI-4334 Tablet
Placebo Comparator: Part B: MAD Cohorts 1-2 ABI-4334 Placebo Tablet; Once-daily doses of placebo matching ABI-4334 will be administered from Day 1 to Day 8.	Drug: ABI-4334 Placebo; Placebo to ABI-4334 Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory results	Up to Day 14

Secondary Outcome Measures

Outcome Measure	Time Frame
SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-4334	before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Maximum Observed Plasma Concentration (Cmax) of ABI-4334	before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Time to Cmax (Tmax) of ABI-4334	before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Apparent Terminal Elimination Half Life (t 1/2) of ABI-4334	before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-4334	before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-4334	before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Comparison of Cmax between fasted and fed treatments of ABI-4334	before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Comparison of AUC between fasted and fed treatments of ABI-4334	before and at pre-specified time points up to 144 hours after dosing
MAD Cohorts 1-2: AUC of ABI-4334	before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: Cmax of ABI-4334	before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: Tmax of ABI-4334	before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: t 1/2 of ABI-4334	before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: CL/F of ABI-4334	before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: Vz/F of ABI-4334	before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8

Collaborators and Investigators

• Sponsor: Assembly Biosciences
• Investigators: Principal Investigator: Edward Gane, New Zealand Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Actual): April 12, 2023
• Study Completion (Actual): April 12, 2023

Study Registration Dates

• First Submitted: October 3, 2022
• First Submitted That Met QC Criteria: October 4, 2022
• First Posted (Actual): October 6, 2022

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: PK; Healthy Subjects; ABI-4334
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Chronic Disease; Hepatitis B; Hepatitis B, Chronic
• Other Study ID Numbers: ABI-4334-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes