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

Back to results

Primary Purpose

Status

Completed

Phase

Phase 1

Locations

New Zealand

Study Type

Interventional

Intervention

ABI-H3733 Liquid Oral Dosage Form

ABI-H3733 Solid Oral Dosage Form

Placebo to ABI-H3733 Liquid Oral Dosage Form

Placebo to ABI-H3733 Solid Oral Dosage Form

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Auckland Clinical Studies

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

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

Part 1: SAD Cohorts 1-7 Placebo Liquid Form

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

Part 1: MAD Cohorts 8-10 Placebo Liquid Form

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

Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form

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

Part 2: Single Dose Fed Cohort 12 Placebo Solid Form

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants with One or More Adverse Events

Number of Participants with One or More Related Adverse Events

Number of Participants with One or More Severe (Grade ≥3) Adverse Events

Secondary Outcome Measures

SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-H3733

SAD Cohorts 1-7: Maximum Plasma Concentration (Cmax) ABI-H3733

SAD Cohorts 1-7: Time of Cmax (Tmax) of ABI-H3733

SAD Cohorts 1-7: Apparent Terminal Elimination Half-life (t1/2) of ABI-H3733

SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-H3733

SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-H3733

MAD Cohorts 8-10: AUC of ABI-H3733

MAD Cohorts 8-10: Cmax Over the Dosing Interval of ABI-H3733

MAD Cohorts 8-10: Tmax of ABI-H3733

MAD Cohorts 8-10: t1/2 of ABI-H3733

Single Dose Cohorts 11-12: AUC of ABI-H3733

Single Dose Cohorts 11-12: Cmax of ABI-H3733

Single Dose Cohorts 11-12: Tmax of ABI-H3733

Single Dose Cohorts 11-12: t1/2 of ABI-H3733

Full Information

NCT ID

NCT04271592

First Posted

February 13, 2020

Last Updated

January 26, 2021

Sponsor

Assembly Biosciences

1. Study Identification

Unique Protocol Identification Number

NCT04271592

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Completed

Study Start Date

May 17, 2020 (Actual)

Primary Completion Date

November 3, 2020 (Actual)

Study Completion Date

January 14, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assembly Biosciences

4. Oversight

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

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Hepatitis B

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 1: SAD Cohorts 1-7 Placebo Liquid Form

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

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

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 1: MAD Cohorts 8-10 Placebo Liquid Form

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

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

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 2: Single Dose Fasted Cohort 11 Placebo Solid Form

Arm Type

Placebo Comparator

Arm Description

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.

Arm Title

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

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 2: Single Dose Fed Cohort 12 Placebo Solid Form

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

ABI-H3733 Liquid Oral Dosage Form

Intervention Description

ABI-H3733 liquid oral dosage form

Intervention Type

Drug

Intervention Name(s)

ABI-H3733 Solid Oral Dosage Form

Intervention Description

ABI-H3733 solid oral dosage form

Intervention Type

Drug

Intervention Name(s)

Placebo to ABI-H3733 Liquid Oral Dosage Form

Intervention Description

Placebo to ABI-H3733 liquid oral dosage form

Intervention Type

Drug

Intervention Name(s)

Placebo to ABI-H3733 Solid Oral Dosage Form

Intervention Description

Placebo to ABI-H3733 solid oral dosage form

Primary Outcome Measure Information:

Title

Number of Participants with One or More Adverse Events

Time Frame

Up to Day 10

Title

Number of Participants with One or More Related Adverse Events

Time Frame

Up to Day 10

Title

Number of Participants with One or More Severe (Grade ≥3) Adverse Events

Time Frame

Up to Day 10

Secondary Outcome Measure Information:

Title

SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

SAD Cohorts 1-7: Maximum Plasma Concentration (Cmax) ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

SAD Cohorts 1-7: Time of Cmax (Tmax) of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

SAD Cohorts 1-7: Apparent Terminal Elimination Half-life (t1/2) of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

MAD Cohorts 8-10: AUC of ABI-H3733

Time Frame

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

Title

MAD Cohorts 8-10: Cmax Over the Dosing Interval of ABI-H3733

Time Frame

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

Title

MAD Cohorts 8-10: Tmax of ABI-H3733

Time Frame

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

Title

MAD Cohorts 8-10: t1/2 of ABI-H3733

Time Frame

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

Title

Single Dose Cohorts 11-12: AUC of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

Single Dose Cohorts 11-12: Cmax of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

Single Dose Cohorts 11-12: Tmax of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

Title

Single Dose Cohorts 11-12: t1/2 of ABI-H3733

Time Frame

before and at pre-specified time points up to 120 hours after dosing

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Katia Alves, MD

Organizational Affiliation

Assembly Biosciences

Official's Role

Study Director

Facility Information:

Facility Name

Auckland Clinical Studies

City

Auckland

Country

New Zealand

12. IPD Sharing Statement

Plan to Share IPD

No

Chronic Hepatitis B

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial