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

NCT04271592 | Completed Phase 1 FDA Drug

• 2 other identifiers: ABI-H3733-101U1111-1246-2965
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (14)

• 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

Study Arms (8)

Part 1: SAD Cohorts 1-7 ABI-H3733 Liquid Form

EXPERIMENTAL

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

Part 1: SAD Cohorts 1-7 Placebo Liquid Form

PLACEBO COMPARATOR

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

Part 1: MAD Cohorts 8-10 ABI-H3733 Liquid Form

EXPERIMENTAL

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

Part 1: MAD Cohorts 8-10 Placebo Liquid Form

PLACEBO COMPARATOR

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

Part 2: Single Dose Fasted Cohort 11 ABI-H3733 Solid Form

EXPERIMENTAL

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

Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form

PLACEBO COMPARATOR

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

Part 2: Single Dose Fed Cohort 12 ABI-H3733 Solid Form

EXPERIMENTAL

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

Part 2: Single Dose Fed Cohort 12 Placebo Solid Form

PLACEBO COMPARATOR

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

Interventions

ABI-H3733 Liquid Oral Dosage Form DRUG

ABI-H3733 liquid oral dosage form

Part 1: MAD Cohorts 8-10 ABI-H3733 Liquid Form; Part 1: SAD Cohorts 1-7 ABI-H3733 Liquid Form

ABI-H3733 Solid Oral Dosage Form DRUG

ABI-H3733 solid oral dosage form

Part 2: Single Dose Fasted Cohort 11 ABI-H3733 Solid Form; Part 2: Single Dose Fed Cohort 12 ABI-H3733 Solid Form

Placebo to ABI-H3733 Liquid Oral Dosage Form DRUG

Placebo to ABI-H3733 liquid oral dosage form

Part 1: MAD Cohorts 8-10 Placebo Liquid Form; Part 1: SAD Cohorts 1-7 Placebo Liquid Form

Placebo to ABI-H3733 Solid Oral Dosage Form DRUG

Placebo to ABI-H3733 solid oral dosage form

Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form; Part 2: Single Dose Fed Cohort 12 Placebo Solid Form

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Assembly Biosciences: lead

Study Sites (1)

Auckland Clinical Studies

Auckland, New Zealand

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Katia Alves, MD

  Assembly Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 17, 2020
• Study Start: May 17, 2020
• Primary Completion: November 3, 2020
• Study Completion: January 14, 2021
• Last Updated: January 27, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)