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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]

2016-003723-38

Secondary ID [2]

NP39305

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Hepatitis B, Chronic

Condition category

Condition code

Infection

Other infectious diseases

Oral and Gastrointestinal

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]

Other interventions

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1: Percentage of SAD Participants With Adverse Events (AEs)

Timepoint [1]

From randomization up to Day 29

Primary outcome [2]

Part 1: Percentage of MAD Participants With AEs

Timepoint [2]

From randomization up to Day 41

Primary outcome [3]

Part 2: Percentage of Chronic Hepatitis B Participants With AEs

Timepoint [3]

From randomization up to Week 12

Primary outcome [4]

Part 1: Percentage of SAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

Timepoint [4]

From randomization up to Day 8

Primary outcome [5]

Part 1: Percentage of MAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

Timepoint [5]

From randomization up to Day 20

Primary outcome [6]

Part 2: Percentage of Chronic Hepatitis B Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

Timepoint [6]

From randomization up to Week 12

Primary outcome [7]

Part 1: Percentage of SAD Participants With Abnormalities in Electrocardiograph (ECG) Parameters

Timepoint [7]

From randomization up to Day 8

Primary outcome [8]

Part 1: Percentage of MAD Participants With Abnormalities in ECG Parameters

Timepoint [8]

From randomization up to Day 20

Primary outcome [9]

Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in ECG Parameters

Timepoint [9]

From randomization up to Week 12

Primary outcome [10]

Part 1: Percentage of SAD Participants With Abnormalities in Vital Signs

Timepoint [10]

From randomization up to Day 8

Primary outcome [11]

Part 1: Percentage of MAD Participants With Abnormalities in Vital Signs

Timepoint [11]

From randomization up to Day 20

Primary outcome [12]

Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in Vital Signs

Timepoint [12]

From randomization up to Week 12

Secondary outcome [1]

Part 1: Maximum Observed Plasma Concentration (Cmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD

Timepoint [1]

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]

Part 2: Cmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

Timepoint [2]

Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

Secondary outcome [3]

Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD

Timepoint [3]

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]

Part 2: Tmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

Timepoint [4]

Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

Secondary outcome [5]

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]

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]

Part 2: AUCinf of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

Timepoint [6]

Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

Secondary outcome [7]

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]

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]

Part 2: AUClast of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

Timepoint [8]

Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

Secondary outcome [9]

Part 1: Half Life (t1/2) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD

Timepoint [9]

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]

Part 2: t1/2 of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

Timepoint [10]

Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

Secondary outcome [11]

Part 1: Total Amount of RO7020531, RO7011785, RO7018822 and RO7033805 in Urine: SAD

Timepoint [11]

0 to 24 hrs Postdose on Day 1

Secondary outcome [12]

Part 1:Mean Concentration of Interferon Alpha (IFN-alpha): SAD and MAD

Timepoint [12]

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]

Part 2: Mean Concentration of IFN-alpha

Timepoint [13]

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]

Part 1: Mean Fold Change From Baseline in Cytokine Markers: SAD and MAD

Timepoint [14]

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]

Part 2: Mean Fold Change From Baseline in Cytokine Markers

Timepoint [15]

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]

Part 1:Mean Fold Change From Baseline in Markers of Transcriptional Responses: SAD and MAD

Timepoint [16]

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]

Part 2: Mean Fold Change From Baseline in Markers of Transcriptional Responses

Timepoint [17]

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]

Effect of RO7020531 Dosing on ECG Parameters (PR [PQ], QRS, QT, QTcF in Miliseconds [ms]) Using Exposure-response Analysis: SAD and MAD

Timepoint [18]

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]

Part 2: Plasma Concentrations of Tenofovir, Tenofovir Alafenamide, Entecavir, Adefovir and Telbivudine

Timepoint [19]

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

12/12/2016

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

15/06/2021

Sample size

Target

Accrual to date

Final

160

Recruitment in Australia

Recruitment state(s)

Recruitment outside Australia

Country [1]

Bulgaria

State/province [1]

Sofia

Country [2]

Hong Kong

State/province [2]

Hong Kong

Country [3]

Hong Kong

State/province [3]

Shatin

Country [4]

Italy

State/province [4]

Emilia-Romagna

Country [5]

Italy

State/province [5]

Lombardia

Country [6]

Netherlands

State/province [6]

Amsterdam

Country [7]

New Zealand

State/province [7]

Auckland

Country [8]

Taiwan

State/province [8]

Tainan

Country [9]

Taiwan

State/province [9]

Taipei City

Country [10]

Taiwan

State/province [10]

Taoyuan

Country [11]

Taiwan

State/province [11]

Xitun Dist.

Country [12]

Thailand

State/province [12]

Bangkok

Country [13]

Thailand

State/province [13]

Chiang Mai

Country [14]

United Kingdom

State/province [14]

Liverpool

Country [15]

United Kingdom

State/province [15]

London

Funding & Sponsors

Primary sponsor type

Commercial sector/industry

Name

Hoffmann-La Roche

Address

Country

Ethics approval

Ethics application status

Summary

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.

Trial website

https://clinicaltrials.gov/study/NCT02956850

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Clinical Trials

Address

Hoffmann-La Roche

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02956850

Trial Review

Registering a new trial?

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