Safety, Tolerability, PK & PD of AB-101 Following Oral Administration in Healthy and CHB Subjects.

Sponsor

Arbutus Biopharma Corporation (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05960240

Collaborator

(none)

164

Enrollment

Location

Arms

Anticipated Duration (Months)

3.8

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-101. Parts 1 and 2 will be a Phase 1a SAD/MAD of AB-101 in healthy adult subjects.

Part 3 will be a Phase 1b dose-ranging assessment of AB-101 in non-cirrhotic Chronic Hepatitis B (CHB) subjects.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis b	Drug: AB-101 Drug: Placebo Drug: Nucleos(t)ide Analogue	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

164 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

A Double-Blind, Randomized, Placebo-Controlled, Single and Multiple Dose Study Evaluating the Safety, Tolerability, PK and PD of AB-101, an Oral PD-L1 Inhibitor, in Healthy Subjects and Subjects With Chronic HBV Infection.

Anticipated Study Start Date :

Sep 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2026

Anticipated Study Completion Date :

Apr 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1	Drug: AB-101 AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents. Drug: Placebo A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study.
Experimental: Part 2	Drug: AB-101 AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents. Drug: Placebo A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study.
Experimental: Part 3	Drug: AB-101 AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents. Drug: Placebo A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study. Drug: Nucleos(t)ide Analogue Nucleos(t)ide analogues (NUCs) are the standard and mostly lifelong treatment for chronic HBeAg-negative hepatitis B.

Arm

Intervention/Treatment

Experimental: Part 1

Drug: AB-101

AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents.

Drug: Placebo

A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study.

Experimental: Part 2

Drug: AB-101

AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents.

Drug: Placebo

A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study.

Experimental: Part 3

Drug: AB-101

AB-101 is an oral small molecule PD-L1 checkpoint inhibitor being developed for the treatment of chronic infection with HBV in combination with other agents.

Drug: Placebo

A placebo is any treatment that has no active properties, such as a sugar pill. We will use matching placebo for this study.

Drug: Nucleos(t)ide Analogue

Nucleos(t)ide analogues (NUCs) are the standard and mostly lifelong treatment for chronic HBeAg-negative hepatitis B.

Outcome Measures

Primary Outcome Measures

Parts 1 and 2: Incidence of adverse events (AEs), serious AEs (SAEs), immune related AEs (irAEs) and discontinuations due to AEs and irAEs. [[Time Frame: Up to 57 (Part 1) or 84 (Part 2) days]]
Part 3: Incidence of AEs, SAEs, irAEs and discontinuations due to AEs and irAEs [[Time Frame: Up to 196 days]]
Parts 1 and 2: Incidence of clinically significant laboratory abnormalities Parts 1 and 2: Incidence of clinically significant laboratory abnormalities [[Time Frame: Up to 57 (Part 1) or 84 (Part 2) days]]
Parts 1 and 2: Incidence of clinically significant changes in vital signs (heart rate, blood pressure, temperature, respiratory rate), physical examinations and electrocardiograms (ECGs) [[Time Frame: Up to 57 (Part 1) or 84 (Part 2) days]]
Part 3: Incidence of clinically significant laboratory abnormalities [[Time Frame: Up to 196 days]]
Part 3: Incidence of clinically significant changes in vital signs (heart rate, blood pressure, temperature, respiratory rate), physical examinations and electrocardiograms (ECGs) [[Time Frame: Up to 196 days]]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria: Part 1 and 2 (Healthy Volunteers)

Male between ages 18-50 years
Willing and able to provide informed consent

Willing to follow protocol-specified contraception requirement

Inclusion Criteria: Part 3 (CHB Subjects)

Male or female subjects between the ages of 18-60 years
Willing to provide informed consent
Chronic HBV infection for at least 6 months
Willing to follow protocol-specified contraception requirement

Exclusion Criteria: Part 1 and 2 (Healthy Volunteers)

Key Exclusion Criteria:

Clinically significant lab abnormalities
A history of clinically significant gastrointestinal, hematologic, renal, hepatic, bronchopulmonary, neurological, psychiatric, cardiovascular, autoimmune or other immune-mediated disease.
HIV or Hep C positive
Known chronic or severe infection or recent significant exposure to infections such as tuberculosis or endemic mycosis, untreated latent infections like tuberculosis, or a positive or indeterminate QuantiFERON test.

Exclusion Criteria: Part 3 (CHB Subjects)

Have extensive fibrosis or cirrhosis of the liver
Have or had liver cancer (hepatocellular carcinoma)
Have a history or current autoimmune disease or has been on immunosuppressive medications within 6 months of the start of the study
Females who breastfeeding, pregnant or who wish to become pregnant during the study
Known chronic or severe infection or recent significant exposure to infections such as tuberculosis or endemic mycosis, untreated latent infections like tuberculosis, or a positive or indeterminate QuantiFERON test.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New Zealand Clinical Research Auckland	Auckland		New Zealand

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:

NCT05960240

Other Study ID Numbers:

AB-101-001

First Posted:

Jul 25, 2023

Last Update Posted:

Jul 28, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

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

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

Additional relevant MeSH terms:

Hepatitis B

Hepatitis B, Chronic

Study Results

No Results Posted as of Jul 28, 2023