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

Arbutus Biopharma

Status and phase: Terminated; Phase 1

Conditions: Chronic Hepatitis

Treatments: Drug: Placebo; Drug: AB-836; Drug: Nucleos(t)ide Analogue

Study type: Interventional

Funder types: Industry

Identifiers

NCT04775797

AB-836-001

Details and patient eligibility

About

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.

Enrollment: 110 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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110 participants in 5 patient groups

Part 1 (Healthy Subjects): Single Ascending Dose (SAD)

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Placebo

Drug: AB-836

Drug: AB-836

Part 2a (Healthy Subjects): Multiple Ascending Dose (MAD)

Experimental group

Description:

Participants in Cohorts C, D and E will receive a once daily dose of AB-836/placebo for 10 days

Treatment:

Drug: Placebo

Drug: Placebo

Drug: AB-836

Drug: AB-836

Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohorts F-H

Experimental group

Description:

Participants in Cohorts F, G, and H will receive multiple doses of AB-836/placebo once daily for 28 days.

Treatment:

Drug: Placebo

Drug: Placebo

Drug: AB-836

Drug: AB-836

Part 3 (Chronic Hepatitis B [CHB] Participants): MAD Cohort I

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: Placebo

Drug: AB-836

Drug: AB-836

Drug: Nucleos(t)ide Analogue

Part 2b (Healthy Subjects): MAD

Experimental group

Description:

Participants in Cohorts J will receive a once daily dose of AB-836/placebo for 35 days

Treatment:

Drug: Placebo

Drug: Placebo

Drug: AB-836

Drug: AB-836