Chronic Hepatitis B
Conditions
Brief summary
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).
Interventions
DRUGRO7565020
RO7565020 will be administered by subcutaneous injection or intravenous infusion.
OTHERPlacebo
Matching placebo will be administered by subcutaneous injection or intravenous infusion.
DRUGNucleos(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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1a: Number of Healthy Volunteers With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to approximately 40 weeks | 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. |
| Part 2a: Number of CHB Participants With AEs and SAEs | Up to approximately 32 weeks | 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. |
| Part 1a: Number of Healthy Volunteers With Adverse Events of Special Interest (AESI) | Up to approximately 40 weeks | 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. |
| Part 2a: Number of CHB Participants With AESI | Up to approximately 32 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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 | IU/mL= international units per milliliter |
| 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 | Up to Day 169 | HBsAg seroconversion was defined as sustained loss of HBsAg and detection of anti-HBs antibody. |
| 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 | — |
| Number of Participants With Anti-Drug Antibodies (ADAs) to RO7565020 | Part 1a: Baseline and post-baseline (up to approximately 40 weeks); Part 2a: Baseline and post-baseline (up to approximately 32 weeks) | 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 2a: Percentage of Participants With HBeAg Seroconversion Among HBeAg-positive Participants at Baseline | Up to Day 169 | HBeAg seroconversion was defined as sustained loss of HBeAg and detection of anti-HBe antibody. |
| 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 | — |
Countries
Hong Kong, New Zealand, South Korea, Spain, Taiwan, Thailand, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
A total of 48 healthy participants (Part 1a) and 12 participants with chronic hepatitis B (CHB) virus infection (Part 2a) took part in the study across 10 investigative sites in Hong Kong, Thailand, New Zealand, Republic of Korea, United States, Spain, and Taiwan from 28 April 2023 to 23 December 2024.
Pre-assignment details
The study consists of 3 parts- Part 1a: single-ascending dose (SAD) and Part 1b: multiple doses in healthy participants, Part 2 (a and b): SAD in participants with CHB, and Part 3: multiple doses in participants with CHB. No participants were enrolled in the Part 1b, Part 2b, and Part 3 as the study was terminated by the sponsor.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 4.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 12 | 4 / 6 | 5 / 6 | 4 / 6 | 6 / 6 | 6 / 6 | 1 / 6 | 2 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
None listed