Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection

Sponsor

Arbutus Biopharma Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04775797

Collaborator

(none)

Enrollment

Locations

Arms

16.2

Anticipated Duration (Months)

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This three-part, Phase 1 protocol will be the first clinical study of AB-836. Parts 1 and 2 will be a Phase 1a SAD/MAD of AB-836 in healthy adult subjects. Part 3 will be a Phase 1b dose-ranging assessment of AB-836 in non-cirrhotic Chronic Hepatitis B (CHB) subjects.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis	Drug: AB-836 Drug: Placebo Drug: Tenofovir Disoproxil Fumarate	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Dose Study Evaluating the Safety, Tolerability, and Pharmacokinetics of AB-836, an HBV Capsid Inhibitor, in Healthy Subjects and Subjects With Chronic HBV Infection

Actual Study Start Date :

Mar 25, 2021

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 (Healthy Subjects): Single Ascending Dose (SAD) Two cohorts (Cohorts A and B) of healthy subjects will receive single doses of AB-836/placebo in an alternating cohort design under fasted conditions. One additional treatment will be administered under fed conditions.	Drug: AB-836 Capsules or Tablets Drug: Placebo Capsules or Tablets
Experimental: Part 2 (Healthy Subjects): Multiple Ascending Dose (MAD) Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days	Drug: AB-836 Capsules or Tablets Drug: Placebo Capsules or Tablets
Experimental: Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days.	Drug: AB-836 Capsules or Tablets Drug: Placebo Capsules or Tablets
Experimental: Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I Participants in Cohort I will receive multiple doses of AB-836/placebo once daily for 28 days in combination with ongoing nucleos(t)ide analog (NA) therapy.	Drug: AB-836 Capsules or Tablets Drug: Placebo Capsules or Tablets
Experimental: Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort J Participants in Cohort J will receive AB-836/placebo and TDF in combination once daily for 28 days.	Drug: AB-836 Capsules or Tablets Drug: Placebo Capsules or Tablets Drug: Tenofovir Disoproxil Fumarate Tablets

Outcome Measures

Primary Outcome Measures

Incidence of TEAEs [Up to 28 days after last dose of AB-836/placebo]
Incidence of discontinuations due to AEs [Up to 28 days after last dose of AB-836/placebo]
Incidence of lab abnormalities [Up to 28 days after last dose of AB-836/placebo]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Healthy Subjects

Male subjects or female subjects not of childbearing potential between 18 and 45 years old.
Free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results.
BMI of 18-32 kg/m2.

CHB Subjects:

Male or female between 18 and 65 years old.
Chronic HBV infection documented as a positive HBsAg, HBV DNA, or HBeAg test at least 6 months prior to the Screening Visit, or a historical liver biopsy consistent with chronic HBV infection
For cohort F, G, H and J:
HBV DNA ≥2,000 IU/mL at Screening (subjects may be either treatment-naïve or treatment-experienced but currently off-treatment).
ALT ≤ 5x ULN
For Cohort I:
HBV DNA <LLOQ at Screening
Subjects must have been receiving either TAF, TDF, or ETV consistently for ≥6 months prior to Day 1 and are willing to continue with the same NA treatment through the final study visit.
ALT ≤ 2.5 x ULN
HbsAg ≥250 IU/mL at screening

Exclusion Criteria:

CHB Subjects

Advanced fibrosis, cirrhosis or other signs of advanced liver disease as assessed by clinical history, ultrasound or FibroScan, or history of cirrhosis or any clinically significant medical condition associated with chronic liver disease.
Co-infection with HIV or other non-B hepatitis viruses.
Any clinically significant or unstable medical condition or illness that could confound study findings.
Subjects who are unwilling to comply with protocol contraception requirements, and female subjects who are pregnant or breastfeeding.
Previous treatment with a capsid inhibitor, core inhibitor, or core protein assembly modifier [CpAM or CAM]) within 6 months of the Day 1 visit, or prior treatment with an HBV-targeted siRNA or antisense oligonucleotide compound at any time.

Contacts and Locations

Locations

	Site	City	Country
1	Queen Mary Hospital	Hong Kong	Hong Kong
2	Arensia Exploratory Medicine	Chisinau	Moldova, Republic of
3	Auckland Clinical Studies	Auckland	New Zealand
4	Arensia Exploratory Medicine	Kapitanivka	Ukraine

Sponsors and Collaborators

Arbutus Biopharma Corporation

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Arbutus Biopharma Corporation

ClinicalTrials.gov Identifier:

NCT04775797

Other Study ID Numbers:

AB-836-001

First Posted:

Mar 1, 2021

Last Update Posted:

Jul 14, 2021

Last Verified:

Jun 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Hepatitis, Chronic

Tenofovir

Study Results

No Results Posted as of Jul 14, 2021