Clinical trial NCT04775797: Safety, Tolerability, and Pharmacokinetics of AB-836 in Healthy Subjects and Subjects With Chronic HBV Infection
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Hepatitis
Lead sponsor: Arbutus Biopharma Corporation
Sponsor class: INDUSTRY
First posted: 2021-03-01
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This three-part, Phase 1 protocol will be the first clinical study of AB-836. Parts 1 and 2a/b 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.


Eligibility criteria: Inclusion Criteria:

* Healthy Subjects

  1. Male and Female (not of childbearing potential in Part 1 and 2a) subjects between 18 and 45 years old
  2. Free from clinically significant illness or disease as determined by their medical history, physical examination, vital signs, and clinical laboratory test results.
  3. BMI of 18-32 kg/m2.
* CHB Subjects:

  1. Male or female between 18 and 65 years old.
  2. 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
  3. For cohort F, G, H:

     1. HBV DNA ≥2,000 IU/mL at Screening (subjects may be either treatment-naïve or treatment-experienced but currently off-treatment).
     2. ALT ≤ 5x ULN
  4. For Cohort I:

     1. HBV DNA \<LLOQ at Screening
     2. 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.
     3. ALT ≤ 2.5 x ULN
  5. HbsAg ≥250 IU/mL at screening

Exclusion Criteria:

* CHB Subjects

  1. 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.
  2. Co-infection with HIV or other non-B hepatitis viruses.
  3. Any clinically significant or unstable medical condition or illness that could confound study findings.
  4. Subjects who are unwilling to comply with protocol contraception requirements, and female subjects who are pregnant or breastfeeding.
  5. 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.

Primary outcomes:
measure: Incidence of TEAEs
timeFrame: Up to 35 days after last dose of AB-836/placebo
measure: Incidence of discontinuations due to AEs
timeFrame: Up to 35 days after last dose of AB-836/placebo
measure: Incidence of lab abnormalities
timeFrame: Up to 35 days after last dose of AB-836/placebo
Secondary outcomes:
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto Liver Center
state: Ontario
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Chisinau
country: Moldova, Republic of
facility: Arensia Exploratory Medicine
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research Auckland
city: Bangkok
country: Thailand
facility: Hospital For Tropical Diseases
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
city: Phitsanulok
country: Thailand
facility: Naresuan University Hospital
city: Kyiv
country: Ukraine
facility: Medical Center of Limited Liability Company Arensia Exploratory Medicine
Study officials:
References: