Study of Imdusiran (AB-729) in Combination With Intermittent Dosing of Durvalumab in Subjects With Chronic HBV Infection

A Phase 2a, Open-Label Multiple Dose Study Evaluating the Safety, Tolerability, and Pharmacodynamics of Imdusiran (AB-729) in Combination With Intermittent Dosing of Durvalumab, a PD-L1 Monoclonal Antibody, in Subjects With Chronic HBV Infection

This is a phase 2a, open-label, multicenter study investigating the safety, tolerability, and antiviral activity of durvalumab administered at targeted times during a 48-week treatment period of imdusiran in virologically-suppressed CHB subjects

Study Overview

• Status: Withdrawn
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Imdusiran; Drug: Durvalumab

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia, 0160
    • Infectious Diseases, AIDS and Clinical Immunology Research Center
  • Tbilisi, Georgia, 0186
    • LLC "Neolab"
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince Of Wales Hospital - The Chinese University Of Hong Kong
• Poland
  • Gdańsk, Poland
    • Punkt Zdrowia Hlebowicz Jakubowski Lekarze Spółka Partnerska
  • Mysłowice, Poland
    • ID Clinic Arkadiusz Pisula
  • Wrocław, Poland
    • Punkt Zdrowia Hlebowicz Jakubowski Lekarze Spółka Partnerska
• Romania
  • Bucharest, Romania
    • Arensia Exploratory Medicine Srl Romania in colaborare cu Institutul National de Boli Infectioase
• Spain
  • Barcelona, Spain
    • Hospital Clinic de Barcelona
  • Barcelona, Spain
    • Hospital Universitario Vall d'Hebron
• Taiwan
  • Chia-Yi City, Taiwan
    • Chia-Yi Christian Hospital
  • Kaohsiung City, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung City, Taiwan
    • China Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei City, Taiwan
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand
    • Siriraj Hospital
  • Bangkok, Thailand
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand
    • The HIV Netherlands Australia Thailand Research Collaboration
  • Khon Kaen, Thailand
    • Srinagarind Hospital
  • Phitsanulok, Thailand
    • Naresuan University Hospital
• United Kingdom
  • London, United Kingdom
    • Royal London Hospital
  • London, United Kingdom
    • Imperial College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female between the ages of 18-65
• Willing and able to provide informed consent
• Willing to follow protocol-specified contraception requirement

Key Exclusion Criteria:

• Have extensive fibrosis or cirrhosis of the liver
• Have or had liver cancer (hepatocellular carcinoma)
• Family history or personal history/current thyroid disease on or off replacement therapy
• Have a history or current autoimmune disease or has been on immunosuppressive medications within 6 months of the start of the study
• Females who are 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Imdusiran 60 mg SC Q8 weeks + nucleos(t)ide analog for 48 weeks + durvalumab at early and mid-treatment period timepoints	Drug: Imdusiran; subcutaneous injection; Drug: Durvalumab; intravenous injection
Experimental: Cohort B; Imdusiran 60 mg SC Q8 weeks + nucleos(t)ide analog for 48 weeks + durvalumab at mid and late-treatment period timepoints	Drug: Imdusiran; subcutaneous injection; Drug: Durvalumab; intravenous injection
Experimental: Cohort C; Imdusiran 60 mg SC Q8 weeks + nucleos(t)ide analog for 48 weeks + durvalumab at 2 late treatment period timepoints	Drug: Imdusiran; subcutaneous injection; Drug: Durvalumab; intravenous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of imdusiran and durvalumab in NA suppressed CHB subjects	• Number of participants with treatment emergent adverse events (TEAEs), immune related adverse events (irAEs), with discontinuations due to adverse events (AEs) and irAEs, with abnormal laboratory tests results, abnormal Vital signs, abnormal physical exam findings and abnormal electrocardiogram (ECG) readings	Up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the effect of imdusiran and durvalumab on HBsAg	• Change in HBsAg levels from baseline during treatment and follow-up	Up to 96 Weeks
To characterize the target engagement (TE) (pharmacodynamics [PD]) of durvalumab in CHB subjects over time	• Measurement of soluble immune marker levels in plasma at multiple timepoints	Up to 48 Weeks
To determine the proportion of subjects who meet NA treatment discontinuation criteria at Week 48	• Proportion of subjects at Week 48 who are HBeAg negative and meet protocol defined ALT, HBV DNA and HBsAg values	Up to Week 48

Collaborators and Investigators

• Sponsor: Arbutus Biopharma Corporation

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Actual): August 1, 2024
• Study Completion (Actual): August 1, 2024

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Chronic Disease; Hepatitis B; Hepatitis B, Chronic; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: AB-729-203

Drug and device information, study documents

• 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