A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7565020 in Healthy Participants and in Participants With Chronic Hepatitis B Virus Infection

A Phase I Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7565020 in Healthy Participants and in Participants With Chronic Hepatitis B Virus Infection

This is a first in human (FIH), multi-center, dose-finding, and dose-escalation Phase I clinical study of RO7565020 to investigate the safety and tolerability and to characterize the pharmacokinetics and pharmacodynamics following single and/or multiple doses of RO7565020 in healthy participants and/or virologically suppressed participants with chronic hepatitis B (CHB).

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: RO7565020; Drug: Nucleos(t)ide analogue (NUC) treatment; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Shatin, New Territories, Hong Kong
    • Prince of Wales Hospital
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research - Auckland
• South Korea
  • Chuncheon, South Korea, 24253
    • Hallym University Chuncheon Sacred Heart Hospital
• Spain
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Hospital Álvaro Cunqueiro
• Taiwan
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation Linkou Branch
• Thailand
  • Bangkok, Thailand, 10700
    • Faculty of Medicine Siriraj Hospital
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital
• United States
  • California
    • San Francisco, California, United States, 94115
      • Quest Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Healthy volunteers:

• Healthy participants
• Body mass index (BMI) between 18 and 32 kg/m^2

CHB participants:

• CHB infection (HBsAg-positive for >/= 6 months)
• On NUC (ETV, TAF, or TDF) monotherapy for >/= 12 months
• Liver biopsy, FibroScan, or equivalent test within the past 6 months demonstrating liver disease consistent with chronic HBV infection without evidence of bridging fibrosis or cirrhosis
• BMI between 18 and 32 kg/m^2

Exclusion Criteria:

Healthy volunteers:

• History of any clinically significant disease
• Concomitant disease that could interfere with treatment or conduct of study
• Use of any treatment within the 2 weeks or within 5 half-lives prior to first dosing (whichever is longer)

CHB participants:

• Evidence of liver cirrhosis or decompensated liver disease
• History or suspicion of hepatocellular carcinoma (HCC)
• History or evidence of a medical condition associated with chronic liver disease other than HBV infection, or clinically significant and not adequately controlled non-hepatic disease
• History of or currently receiving any systemic anti-neoplastic or immune-modulatory treatment within the 8 weeks prior to the first dosing or the expectation that such treatment will be needed at any time during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Matching placebo will be administered by subcutaneous injection or intravenous infusion.
Experimental: RO7565020	Drug: RO7565020; RO7565020 will be administered by subcutaneous injection or intravenous infusion.; Drug: Nucleos(t)ide analogue (NUC) treatment; NUC treatment, including tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), or entecavir (ETV), will be administered orally per local prescribing information.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1a: Number of Healthy Volunteers With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptoms, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention.	Up to approximately 40 weeks
Part 2a: Number of CHB Participants With AEs and SAEs	An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptoms, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention.	Up to approximately 32 weeks
Part 1a: Number of Healthy Volunteers With Adverse Events of Special Interest (AESI)	An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptoms, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AESI includes elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value in combination with either an elevated bilirubin value or clinical jaundice and suspected transmission of an infectious agent by the study treatment.	Up to approximately 40 weeks
Part 2a: Number of CHB Participants With AESI	An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptoms, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AESI includes elevated ALT or AST value in combination with either an elevated bilirubin value or clinical jaundice and suspected transmission of an infectious agent by the study treatment.	Up to approximately 32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1a (SC Cohorts) and Part 2a: Time to Maximum Concentration (Tmax) of RO7565020		Part 1a: Predose, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 21, 29, 57, 85, 141, 197, and 253. Part 2a: Predose, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, and 169
Part 1a (IV Cohorts): Tmax of RO7565020		Predose, 0.08, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 21, 29, 57, 85, 141, 197, and 253
Parts 1a and 2a: Maximum Serum Concentration (Cmax) of RO7565020		Both Part 1a & 2a Cohorts: Predose, 1, 4, 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 29, 57, 85, & 141. Additionally, Part 1a: Days 21, 197, & 253; Part 2a: Days 22, 113, & 169; IV Cohorts: 0.08 hours after start of infusion, Days 21, 197, & 253
Parts 1a and 2a: Area Under the Time-concentration Curve From Time 0 to Time of Last Sampling Point or Last Quantifiable Sample, Whichever Comes First (AUC0-last) of RO7565020		Both Part 1a & 2a Cohorts: Predose, 1, 4, 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 29, 57, 85, & 141. Additionally, Part 1a: Days 21, 197, & 253; Part 2a: Days 22, 113, & 169; IV Cohorts: 0.08 hours after start of infusion, Days 21, 197, & 253
Parts 1a and 2a: Area Under the Time-concentration Curve From Time 0 to Infinity (AUC0-inf) of RO7565020		Both Part 1a & 2a Cohorts: Predose, 1, 4, 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 29, 57, 85, & 141. Additionally, Part 1a: Days 21, 197, & 253; Part 2a: Days 22, 113, & 169; IV Cohorts: 0.08 hours after start of infusion, Days 21, 197, & 253
Parts 1a and 2a: Terminal Half-life (t1/2) of RO7565020		Both Part 1a & 2a Cohorts: Predose, 1, 4, 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 29, 57, 85, & 141. Additionally, Part 1a: Days 21, 197, & 253; Part 2a: Days 22, 113, & 169; IV Cohorts: 0.08 hours after start of infusion, Days 21, 197, & 253
Part 1a (IV Cohorts): Volume of Distribution (Vss) of RO7565020		Predose, 0.08, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 21, 29, 57, 85, 141, 197 and 253
Part 1a (IV Cohorts): Clearance (CL) of RO7565020		Predose, 0.08, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 21, 29, 57, 85, 141, 197 and 253
Part 1a (SC Cohorts) and Part 2a: Apparent Clearance (CL/F) of RO7565020		Part 1a: Predose, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 21, 29, 57, 85, 141, 197, and 253. Part 2a: Predose, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, and 169
Part 1a (SC Cohorts) and Part 2a: Apparent Volume of Distribution (Vz/F) at Terminal Phase of RO7565020		Part 1a: Predose, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 21, 29, 57, 85, 141, 197, and 253. Part 2a: Predose, 1, 4, and 8 hours post-dose on Day 1; Days 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, and 169
Part 2a: Change From Baseline in Serum Quantitative Hepatitis B Surface Antigen (HBsAg)	IU/mL= international units per milliliter	Baseline, 4- and 8-hours post-dose on Day 1; subsequently on Days 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, and 169
Part 2a: Maximum Reduction From Baseline in Serum HBsAg		Up to Day 169
Part 2a: Percentage of Participants With HBsAg Loss		Up to Day 169
Part 2a: Percentage of Participants With HBsAg Seroconversion	HBsAg seroconversion was defined as sustained loss of HBsAg and detection of anti-HBs antibody.	Up to Day 169
Part 2a: Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss Among HBeAg-positive Participants at Baseline		At Days 2, 3, 4, 8, 15, 22, 29, 57, 85, 113, 141, and 169
Part 2a: Percentage of Participants With HBeAg Seroconversion Among HBeAg-positive Participants at Baseline	HBeAg seroconversion was defined as sustained loss of HBeAg and detection of anti-HBe antibody.	Up to Day 169
Number of Participants With Anti-Drug Antibodies (ADAs) to RO7565020	The number of ADA-positive participants at baseline (baseline prevalence) and after drug administration was determined in participants exposed to RO7565020 (post-baseline). Participants were considered ADA positive if they had ADA negative or have missing data at baseline but develop an ADA response following study treatment administration (treatment-induced ADA response), or if they are ADA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold (e.g., ≥ 0.60-titer units) greater than the titer of the baseline sample (treatment enhanced ADA response).	Part 1a: Baseline and post-baseline (up to approximately 40 weeks); Part 2a: Baseline and post-baseline (up to approximately 32 weeks)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2023
• Primary Completion (Actual): December 23, 2024
• Study Completion (Actual): December 23, 2024

Study Registration Dates

• First Submitted: February 28, 2023
• First Submitted That Met QC Criteria: February 28, 2023
• First Posted (Actual): March 10, 2023

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis B; Hepatitis B, Chronic; Amino Acids, Peptides, and Proteins; Proteins; DNA-Binding Proteins; Carrier Proteins; Calcium-Binding Proteins; Therapeutics; Nucleobindins
• Other Study ID Numbers: BP44118; EU trial number (Other Identifier: 2023-510333-28-00)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No