A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABI-H3733 in Healthy Adults

A Phase 1, Randomized, Blinded, Placebo-Controlled, Single and Multiple Dose Escalation and Food Effect Study of ABI-H3733 in Healthy Subjects

This study is designed to assess safety, tolerability, pharmacokinetics (PK), formulation (liquid and solid oral forms) and food effect of ABI-H3733 in healthy participants. Part 1 includes evaluation of the safety, tolerability, and PK of ABI-H3733 during single ascending dose (SAD) and multiple-ascending dose (MAD) administration of the oral liquid formulation. Part 2 includes assessment of a solid dosage formulation of ABI-H3733 in participants under fasted conditions or after a high-fat meal. Optional cohorts may be enrolled in Parts 1 and 2 of the study to explore additional dose levels, solid oral dosage formulations, or for cohort expansion.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: ABI-H3733 Liquid Oral Dosage Form; Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form; Drug: ABI-H3733 Solid Oral Dosage Form; Drug: Placebo to ABI-H3733 Solid Oral Dosage Form

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Auckland Clinical Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• No clinically significant abnormal findings on physical exam, medical history, or clinical laboratory results at screening.

Exclusion Criteria:

• Positive test results for human immunodeficiency virus (HIV) or hepatitis B or C.
• History of or current persistent drug or alcohol abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1: SAD Cohorts 1-7 ABI-H3733 Liquid Form; A single dose of ABI-H3733 liquid oral dosage form administered on Day 1. Cohort 1 will receive a 100-mg dose. Subsequent cohorts 2-7 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.	Drug: ABI-H3733 Liquid Oral Dosage Form; ABI-H3733 liquid oral dosage form
PLACEBO_COMPARATOR: Part 1: SAD Cohorts 1-7 Placebo Liquid Form; A single dose of placebo matching ABI-H3733 liquid oral dosage form will be administered on Day 1. Cohort 1 will receive a 100-mg dose. Subsequent cohorts 2-7 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.	Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form; Placebo to ABI-H3733 liquid oral dosage form
EXPERIMENTAL: Part 1: MAD Cohorts 8-10 ABI-H3733 Liquid Form; Once-daily doses of ABI-H3733 liquid oral dosage form will be administered from Day 1 to Day 5. Cohort 8 will receive a dose determined from evaluation of the data from the SAD cohorts. Subsequent cohorts 9 and 10 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.	Drug: ABI-H3733 Liquid Oral Dosage Form; ABI-H3733 liquid oral dosage form
PLACEBO_COMPARATOR: Part 1: MAD Cohorts 8-10 Placebo Liquid Form; Once-daily doses of placebo matching ABI-H3733 liquid oral dosage form will be administered from Day 1 to Day 5. Cohort 8 will receive a dose determined from evaluation of the data from the SAD cohorts. Subsequent cohorts 9 and 10 will receive a ≤3-fold increase in dose from the previous cohort; the dose will be determined by evaluation of safety and PK data from previous cohorts.	Drug: Placebo to ABI-H3733 Liquid Oral Dosage Form; Placebo to ABI-H3733 liquid oral dosage form
EXPERIMENTAL: Part 2: Single Dose Fasted Cohort 11 ABI-H3733 Solid Form; A single dose of ABI-H3733 solid oral dosage form will be administered in a fasted state on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.	Drug: ABI-H3733 Solid Oral Dosage Form; ABI-H3733 solid oral dosage form
PLACEBO_COMPARATOR: Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form; A single dose of placebo matching ABI-H3733 liquid oral dosage form will be administered in a fasted state on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.	Drug: Placebo to ABI-H3733 Solid Oral Dosage Form; Placebo to ABI-H3733 solid oral dosage form
EXPERIMENTAL: Part 2: Single Dose Fed Cohort 12 ABI-H3733 Solid Form; A single dose of ABI-H3733 solid oral dosage form will be administered after a high-fat meal on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.	Drug: ABI-H3733 Solid Oral Dosage Form; ABI-H3733 solid oral dosage form
PLACEBO_COMPARATOR: Part 2: Single Dose Fed Cohort 12 Placebo Solid Form; A single dose of placebo matching ABI-H3733 solid oral dosage form will be administered after a high-fat meal on Day 1. The decision to proceed with Part 2 and the dose administered will be determined after evaluation of cumulative safety and PK data from Part 1.	Drug: Placebo to ABI-H3733 Solid Oral Dosage Form; Placebo to ABI-H3733 solid oral dosage form

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with One or More Adverse Events	Up to Day 10
Number of Participants with One or More Related Adverse Events	Up to Day 10
Number of Participants with One or More Severe (Grade ≥3) Adverse Events	Up to Day 10

Secondary Outcome Measures

Outcome Measure	Time Frame
SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
SAD Cohorts 1-7: Maximum Plasma Concentration (Cmax) ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
SAD Cohorts 1-7: Time of Cmax (Tmax) of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
SAD Cohorts 1-7: Apparent Terminal Elimination Half-life (t1/2) of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
MAD Cohorts 8-10: AUC of ABI-H3733	before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5
MAD Cohorts 8-10: Cmax Over the Dosing Interval of ABI-H3733	before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5
MAD Cohorts 8-10: Tmax of ABI-H3733	before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5
MAD Cohorts 8-10: t1/2 of ABI-H3733	before and at pre-specified time points up to 24 hours after dosing on Day 1; before and up to 120 hours after dosing on Day 5
Single Dose Cohorts 11-12: AUC of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
Single Dose Cohorts 11-12: Cmax of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
Single Dose Cohorts 11-12: Tmax of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing
Single Dose Cohorts 11-12: t1/2 of ABI-H3733	before and at pre-specified time points up to 120 hours after dosing

Collaborators and Investigators

• Sponsor: Assembly Biosciences
• Investigators: Study Director: Katia Alves, MD, Assembly Biosciences

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 17, 2020
• Primary Completion (ACTUAL): November 3, 2020
• Study Completion (ACTUAL): January 14, 2021

Study Registration Dates

• First Submitted: February 13, 2020
• First Submitted That Met QC Criteria: February 13, 2020
• First Posted (ACTUAL): February 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 26, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Hepatitis B; Hepatitis B, Chronic
• Other Study ID Numbers: ABI-H3733-101; U1111-1246-2965 (OTHER: World Health Organization)

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