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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02956850




Registration number
NCT02956850
Ethics application status
Date submitted
3/11/2016
Date registered
6/11/2016
Date last updated
8/02/2024

Titles & IDs
Public title
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
Scientific title
A Phase I, Sponsor-Open, Investigator-Blinded, Subject-Blinded, Multi-Center, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral Administration of RO7020531: (1). Single and Multiple Ascending Doses in Healthy Male and Female Subjects; (2). 6-week Treatment of Patients With Chronic Hepatitis B Virus Infection
Secondary ID [1] 0 0
2016-003723-38
Secondary ID [2] 0 0
NP39305
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B, Chronic 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Placebo
Treatment: Drugs - RO7020531

Experimental: 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.

Experimental: 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.

Experimental: 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.


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

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

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Percentage of SAD Participants With Adverse Events (AEs)
Timepoint [1] 0 0
From randomization up to Day 29
Primary outcome [2] 0 0
Part 1: Percentage of MAD Participants With AEs
Timepoint [2] 0 0
From randomization up to Day 41
Primary outcome [3] 0 0
Part 2: Percentage of Chronic Hepatitis B Participants With AEs
Timepoint [3] 0 0
From randomization up to Week 12
Primary outcome [4] 0 0
Part 1: Percentage of SAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results
Timepoint [4] 0 0
From randomization up to Day 8
Primary outcome [5] 0 0
Part 1: Percentage of MAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results
Timepoint [5] 0 0
From randomization up to Day 20
Primary outcome [6] 0 0
Part 2: Percentage of Chronic Hepatitis B Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results
Timepoint [6] 0 0
From randomization up to Week 12
Primary outcome [7] 0 0
Part 1: Percentage of SAD Participants With Abnormalities in Electrocardiograph (ECG) Parameters
Timepoint [7] 0 0
From randomization up to Day 8
Primary outcome [8] 0 0
Part 1: Percentage of MAD Participants With Abnormalities in ECG Parameters
Timepoint [8] 0 0
From randomization up to Day 20
Primary outcome [9] 0 0
Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in ECG Parameters
Timepoint [9] 0 0
From randomization up to Week 12
Primary outcome [10] 0 0
Part 1: Percentage of SAD Participants With Abnormalities in Vital Signs
Timepoint [10] 0 0
From randomization up to Day 8
Primary outcome [11] 0 0
Part 1: Percentage of MAD Participants With Abnormalities in Vital Signs
Timepoint [11] 0 0
From randomization up to Day 20
Primary outcome [12] 0 0
Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in Vital Signs
Timepoint [12] 0 0
From randomization up to Week 12
Secondary outcome [1] 0 0
Part 1: Maximum Observed Plasma Concentration (Cmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Timepoint [1] 0 0
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Secondary outcome [2] 0 0
Part 2: Cmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Timepoint [2] 0 0
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Secondary outcome [3] 0 0
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Timepoint [3] 0 0
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Secondary outcome [4] 0 0
Part 2: Tmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Timepoint [4] 0 0
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Secondary outcome [5] 0 0
Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Timepoint [5] 0 0
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Secondary outcome [6] 0 0
Part 2: AUCinf of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Timepoint [6] 0 0
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Secondary outcome [7] 0 0
Part 1: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Timepoint [7] 0 0
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Secondary outcome [8] 0 0
Part 2: AUClast of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Timepoint [8] 0 0
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Secondary outcome [9] 0 0
Part 1: Half Life (t1/2) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Timepoint [9] 0 0
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Secondary outcome [10] 0 0
Part 2: t1/2 of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Timepoint [10] 0 0
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Secondary outcome [11] 0 0
Part 1: Total Amount of RO7020531, RO7011785, RO7018822 and RO7033805 in Urine: SAD
Timepoint [11] 0 0
0 to 24 hrs Postdose on Day 1
Secondary outcome [12] 0 0
Part 1:Mean Concentration of Interferon Alpha (IFN-alpha): SAD and MAD
Timepoint [12] 0 0
SAD: Predose, 2, 6, 12 and 24 hrs Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20
Secondary outcome [13] 0 0
Part 2: Mean Concentration of IFN-alpha
Timepoint [13] 0 0
Predose, 6, 8 and 24 hrs Postdose on Day 1; Predose, 4-6, 24 hrs Postdose on Days 3, 7 and 21; Predose, 6, 24 hrs Postdose on Day 41
Secondary outcome [14] 0 0
Part 1: Mean Fold Change From Baseline in Cytokine Markers: SAD and MAD
Timepoint [14] 0 0
SAD: Predose, 2, 6, 12, 24, 48 (only Neopterin) and 96 hrs (only Neopterin) Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20
Secondary outcome [15] 0 0
Part 2: Mean Fold Change From Baseline in Cytokine Markers
Timepoint [15] 0 0
Predose, 6, 8 and 24 hrs Postdose on Day 1; Predose, 4-6, 24 hrs Postdose on Days 3, 7 and 21; Predose, 6, 24 hrs Postdose on Day 41
Secondary outcome [16] 0 0
Part 1:Mean Fold Change From Baseline in Markers of Transcriptional Responses: SAD and MAD
Timepoint [16] 0 0
SAD: Predose, 2, 6, 12 and 24 Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20
Secondary outcome [17] 0 0
Part 2: Mean Fold Change From Baseline in Markers of Transcriptional Responses
Timepoint [17] 0 0
Predose, 6, 8, 24 hrs postdose on Day 1; Predose, 4-6, 24 hrs postdose on Days 3, 7, 21; Predose, 6, 24 hrs postdose on Day 41
Secondary outcome [18] 0 0
Effect of RO7020531 Dosing on ECG Parameters (PR [PQ], QRS, QT, QTcF in Miliseconds [ms]) Using Exposure-response Analysis: SAD and MAD
Timepoint [18] 0 0
SAD: Predose, 0.5, 1, 2, 4, 6, 12, 24 and 48 hrs Post dose on Day 1; MAD: Predose, 0.5, 1,2,4 and 12 hrs Postdose on Day 1 and 13; Predose, 2 and 6 hrs Postdose on Day 3, Predose, 6 and 24 hrs Postdose on Day , 7, 9, and 11
Secondary outcome [19] 0 0
Part 2: Plasma Concentrations of Tenofovir, Tenofovir Alafenamide, Entecavir, Adefovir and Telbivudine
Timepoint [19] 0 0
Pre-dose and 2-4 hours post-dose on Day 1, Day 21 and Day 41

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Sofia
Country [2] 0 0
Hong Kong
State/province [2] 0 0
Hong Kong
Country [3] 0 0
Hong Kong
State/province [3] 0 0
Shatin
Country [4] 0 0
Italy
State/province [4] 0 0
Emilia-Romagna
Country [5] 0 0
Italy
State/province [5] 0 0
Lombardia
Country [6] 0 0
Netherlands
State/province [6] 0 0
Amsterdam
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland
Country [8] 0 0
Taiwan
State/province [8] 0 0
Tainan
Country [9] 0 0
Taiwan
State/province [9] 0 0
Taipei City
Country [10] 0 0
Taiwan
State/province [10] 0 0
Taoyuan
Country [11] 0 0
Taiwan
State/province [11] 0 0
Xitun Dist.
Country [12] 0 0
Thailand
State/province [12] 0 0
Bangkok
Country [13] 0 0
Thailand
State/province [13] 0 0
Chiang Mai
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Liverpool
Country [15] 0 0
United Kingdom
State/province [15] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.