A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531

NCT ID: NCT02956850

Last Updated: 2024-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-12
• Study Completion Date: 2021-06-15

Brief Summary

This sponsor-open, investigator- and participant-blinded, multi-center study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7020531 in healthy participants and in participants with chronic hepatitis B. Part I will be conducted in two portions: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) which will include only healthy volunteers. Part II will commence after completion of the MAD portion of Part I and will include only Chronic Hepatitis B (CHB) participants.

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part I: SAD in Healthy Volunteers

Healthy volunteers will receive single dose of RO7020531 or matching placebo orally on Day 1 of each cohort. A planned dose-escalation sequence for SAD is 3 milligrams (mg), 10 mg, 20 mg, 40 mg, 60 mg, 100 mg, 140 mg, and 170 mg.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: OTHER

Placebo matching to RO7020531 will be administered as per schedule specified in the respective arm.

RO7020531

Intervention Type: DRUG

RO7020531 will be administered as per schedule specified in the respective arm.

Part I: MAD in Healthy Volunteers

Healthy volunteers will receive RO7020531 (100 mg, 140 mg, and 170 mg as selected based on safety, pharmacokinetic (PK) and pharmacodynamic (PD) data of SAD cohorts) or matching placebo orally every other day (QOD) from Day 1 through to Day 13.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: OTHER

Placebo matching to RO7020531 will be administered as per schedule specified in the respective arm.

RO7020531

Intervention Type: DRUG

RO7020531 will be administered as per schedule specified in the respective arm.

Part II: CHB Participants

CHB participants will receive RO7020531 (150 mg and 170 mg as selected based on safety, PK and PD data of MAD cohorts) or matching placebo orally QOD from Day 1 through to Day 41, unless in Cohort 4 in case of once a week (QW) dosing as dose modification.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: OTHER

Placebo matching to RO7020531 will be administered as per schedule specified in the respective arm.

RO7020531

Intervention Type: DRUG

RO7020531 will be administered as per schedule specified in the respective arm.

Interventions

Placebo

Placebo matching to RO7020531 will be administered as per schedule specified in the respective arm.

Intervention Type: OTHER

RO7020531

RO7020531 will be administered as per schedule specified in the respective arm.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Part 1: SAD and MAD in Healthy Volunteers

• Non-smokers, or use of less than (<) 10 cigarettes (or equivalent nicotine-containing product) per day
• Negative Anti-Nuclear Antibody (ANA) test; or positive with dilutions not greater than 1:40 and with no associated history or symptoms of potential connective tissue disease or other immune-mediated diseases

Part 2: CHB Participants

• CHB infection (positive test for Hepatitis B surface antigen [HBsAg] for more than 6 months prior to randomization)
• For Cohort 1, 2, 3 and 4: HBsAg detectable at screening
• For Cohort 1, 2 and 3: Hepatitis B virus deoxyribose nuclic acid (HBV DNA) < 90 international unit per milliliter (IU/mL) for at least 6 months prior to randomization; HBV DNA < 90 IU/mL at screening by Roche Cobas assay
• For Cohort 4: HBV DNA at screening >= 2 × 10*4 IU/mL for HBeAg positive and >= 2 x 10*3 IU/mL for hepatitis B e antigen (HBeAg) negative participants
• For Cohort 1, 2 and 3: Alanine amino transferase (ALT) =<1.5 × upper limit of normal (ULN) during the 6 months prior to randomization confirmed by two measurements separated by at least 14 days; ALT at screening =< 1.5 × ULN.
• For Cohort 4: ALT and aspartate aminotransferase (AST) at screening and Day -1 visit: =< 5 × ULN.
• Negative ANA test; or positive with dilutions not greater than 1:40 and with no associated history or symptoms of potential connective tissue disease or other immune-mediated diseases
• Liver biopsy, Fibroscan® or equivalent elastography test obtained within 6 months prior to randomization demonstrating liver disease consistent with chronic HBV infection with absence of cirrhosis and absence of extensive bridging fibrosis (cirrhosis or extensive bridging fibrosis are defined as greater than or equal to (>/=) Metavir 3, recommended cut-off for Fibroscan 8.5 kilopascals [kPa])
• For Cohort 1, 2 and 3: On treatment with tenofovir, entecavir, adefovir, or telbivudine, either as single agents or in combination, for at least 6 months
• For Cohort 4: Hepatitis B virus (HBV) treatment naïve or not on any anti-HBV treatment for the past 6 months

Exclusion Criteria

Part 1: SAD and MAD in Healthy Volunteers

• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease); clinically significant psychiatric disease, acute infection (e.g., influenza), gastrointestinal (GI) disease (including inflammatory bowel disease, peptic ulcer disease, GI hemorrhage)
• History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids, IFN or pegylated interferon [PEG-IFN]) within the 8 weeks prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
• Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study
• Positive Hepatitis A virus antibody (HAV Ab IgM), HBsAg, Hepatitis C antibody (HCV Ab), or positive for human immunodeficiency virus (HIV) at screening
• History of clinically significant thyroid disease; also, participants with clinically significant elevated thyroid-stimulating hormone (TSH) concentrations at screening
• Positive results for anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) or thyroid peroxidase antibody

Part 2: CHB Participants

• History of liver cirrhosis
• History or other evidence of bleeding from esophageal varices
• Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or clinical evidence such as ascites or varices)
• History or other evidence of a medical condition associated with chronic liver disease other than HBV infection (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure, thalassemia, nonalcoholic steato-hepatitis, etc.). A clinical diagnosis of fatty liver is allowed provided that non alcoholic steatohepatitis (NASH) has been excluded by liver biopsy.
• Documented history or other evidence of metabolic liver disease within one year of randomization
• Positive test for Hepatitis A virus (IgM anti-HAV), Hepatitis C virus (HCV), Hepatitis D virus, Hepatitis E virus (HEV), or human immunodeficiency virus (HIV).
• History of or suspicion of hepatocellular carcinoma or alpha fetoprotein >/=13 nanograms per milliliter (ng/mL) at screening
• History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease); clinically significant psychiatric disease; acute infection (e.g., influenza); GI disease (including inflammatory bowel disease, peptic ulcer disease, GI hemorrhage, or history of pancreatitis); clinically significant cardiovascular (including postural hypotension), endocrine, renal, ocular, pulmonary or neurological disease.
• History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids,IFN or PEG-IFN) within the 8 weeks prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
• Cohort 4: Concurrent HBV treatments
• History of organ transplantation
• Clinically significant thyroid disease; also, participants with clinically significant elevated TSH concentrations at screening
• Positive results for AMA, ASMA or thyroid peroxidase antibody

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Gastroenterology department, Second clinic of internal diseases

Sofia, , Bulgaria

COMAC Medical; Clinical Research Unit for Phase I

Sofia, , Bulgaria

Queen Mary Hospital

Hong Kong, , Hong Kong

The Chinese University of Hong Kong

Shatin, , Hong Kong

Azienda Ospedaliero Universitaria Di Modena Policlinico; U.O. Farmacia

Modena, Emilia-Romagna, Italy

ASST PAPA GIOVANNI XXIII; Epatologia e gastroenterologia pediatrica e dei trapianti

Bergamo, Lombardy, Italy

Medicina Generale ed Epatologia (Humanitas-Rozzano)

Rozzano, Lombardy, Italy

Academisch Medisch Centrum Universiteit Amsterdam; Dermatology and VU University Medical Center

Amsterdam, , Netherlands

Auckland Clinical Studies

Auckland, , New Zealand

National Cheng Kung University Hospital

Tainan City, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Taichung Veterans General Hospital

Xitun Dist., , Taiwan

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Royal Liverpool University Hospital

Liverpool, , United Kingdom

King College Hospital NHS Foundation Trust

London, , United Kingdom

Countries

Bulgaria; Hong Kong; Italy; Netherlands; New Zealand; Taiwan; Thailand; United Kingdom

References

Yuen MF, Balabanska R, Cottreel E, Chen E, Duan D, Jiang Q, Patil A, Triyatni M, Upmanyu R, Zhu Y, Canducci F, Gane EJ. TLR7 agonist RO7020531 versus placebo in healthy volunteers and patients with chronic hepatitis B virus infection: a randomised, observer-blind, placebo-controlled, phase 1 trial. Lancet Infect Dis. 2023 Apr;23(4):496-507. doi: 10.1016/S1473-3099(22)00727-7. Epub 2022 Dec 9.

Reference Type: DERIVED

PMID: 36509100 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2016-003723-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NP39305

Identifier Type: -

Identifier Source: org_study_id