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

Phase 1TerminatedNCT05763576

Hoffmann-La Roche60 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Chronic Hepatitis B

Interventions

RO7565020DRUG

RO7565020 will be administered by subcutaneous injection or intravenous infusion.

PlaceboOTHER

Matching placebo will be administered by subcutaneous injection or intravenous infusion.

Nucleos(t)ide analogue (NUC) treatmentDRUG

NUC treatment, including tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), or entecavir (ETV), will be administered orally per local prescribing information.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (9)

Quest Clinical Research

San Francisco, California, United States

Queen Mary Hospital

Hong Kong, Hong Kong

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

New Zealand Clinical Research - Auckland

Auckland, New Zealand

Outcomes

Primary Outcomes

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.

Time frame: Up to approximately 40 weeks

Part 2a: Number of CHB Participants With AEs and SAEs

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

Part 1a (SC Cohorts) and Part 2a: Time to Maximum Concentration (Tmax) of RO7565020

Time frame: 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

Time frame: 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

Time frame: 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

Parts 1a and 2a: Area Under the Time-concentration Curve From Time 0 to Infinity (AUC0-inf) of RO7565020

Parts 1a and 2a: Terminal Half-life (t1/2) of RO7565020

Part 1a (IV Cohorts): Volume of Distribution (Vss) of RO7565020

Time frame: 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

Time frame: 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 (SC Cohorts) and Part 2a: Apparent Volume of Distribution (Vz/F) at Terminal Phase of RO7565020

Part 2a: Change From Baseline in Serum Quantitative Hepatitis B Surface Antigen (HBsAg)

IU/mL= international units per milliliter

Time frame: 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

Time frame: Up to Day 169

Part 2a: Percentage of Participants With HBsAg Loss

Time frame: 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.

Time frame: Up to Day 169

Part 2a: Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss Among HBeAg-positive Participants at Baseline

Time frame: 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.

Time frame: 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).

Time frame: Part 1a: Baseline and post-baseline (up to approximately 40 weeks); Part 2a: Baseline and post-baseline (up to approximately 32 weeks)