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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02952924




Registration number
NCT02952924
Ethics application status
Date submitted
1/11/2016
Date registered
2/11/2016
Date last updated
31/10/2024

Titles & IDs
Public title
A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7049389 in Healthy Volunteers and Chronic Hepatitis B Virus (HBV) Infected Participants
Scientific title
A Safety, Tolerability, Pharmacokinetics and Efficacy Study of ro7049389 in: (1) Single- (With or Without Food) and Multiple- (With Midazolam) Ascending Doses in Healthy Volunteers; (2) Patients Chronically Infected With Hepatitis b Virus (3) Patients With Chronic Hepatitis B.
Secondary ID [1] 0 0
YP39364
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
Treatment: Drugs - Midazolam
Other interventions - Placebo
Treatment: Drugs - RO7049389

Placebo comparator: Parts 1a and 1b: SAD in Healthy Volunteers (Placebo) - In Part 1a, participants will receive a single oral dose of placebo matching to RO7049389 film coated tablet on Day 1. In Part 1b, minimum 8 participants from Part 1a will be selected and 2 of whom will receive another single dose of placebo matching to RO7049389 on Day 16 after eating the standard United States - Food and Drug Administration (US FDA)-recommended high-fat and high-calorie breakfast.

Experimental: Parts 1a and 1b: SAD in Healthy Volunteers (RO7049389) - In Part 1a, participants will receive a single oral dose of RO7049389 film coated tablet on Day 1 in dose-escalation cohorts with a starting dose of 150 milligrams (mg). The doses for subsequent cohorts will be defined by an adaptive approach based on the safety and PK data in previously-dosed healthy volunteers. In Part 1b, minimum 8 participants from Part 1a will be selected and 6 of whom will receive another single dose of RO7049389 on Day 16 after eating the standard US FDA-recommended high-fat and high-calorie breakfast.

Placebo comparator: Part 1c: MAD in Healthy Volunteers (Placebo) - Participants will receive placebo matching to RO7049389 film coated tablet from Days 1 to 13 (either once a day \[QD\] or twice a day \[BID\]) and a single dose of placebo matching to RO7049389 film coated tablet in the morning of Day 14. Participants will also receive a single dose of midazolam solution (100 micrograms \[mcg\]) on Day -1 and Day 14.

Experimental: Part 1c: MAD in Healthy Volunteers (RO7049389) - Participants will receive RO7049389 film coated tablet from Days 1 to 13 (either QD or BID; dose and regimen will be decided based on the available PK and safety data) and a single dose of RO7049389 film coated tablet in the morning of Day 14. Participants will also receive a single dose of midazolam solution (100 mcg) on Day -1 and Day 14.

Placebo comparator: Part 2: POM in Chronic HBV Participants (Placebo) - Participants will receive placebo matching to RO7049389 film coated tablet from Days 1 to 27 (either QD or BID) and a single dose of placebo matching to RO7049389 film coated tablet in the morning of Day 28.

Experimental: Part 2: POM in Chronic HBV Participants (RO7049389) - Participants will receive RO7049389 film coated tablet from Days 1 to 27 (either QD or BID; dose and regimen will be decided based on the available PK and safety data) and a single dose of RO7049389 film coated tablet in the morning of Day 28.

Experimental: Part 3: POM in NUC-Suppressed CHB Participants (Cohort A) - Participants will receive RO7049389 on top of a NUC for 48 weeks at a dose determined from Part 2. NUC therapy will be administered per local label or guidelines.

Experimental: Part 3: POM in Treatment-Naive CHB Participants (Cohort B) - Participants will receive RO7049389 for 4 weeks, followed by RO7049389 with an added NUC for 44 weeks. RO7049389 will be administered at a dose determined from Part 2. NUC therapy will be administered per local label or guidelines.

Experimental: Part 3: POM in Treatment-Naive CHB Participants (Cohort C) - Participants will receive RO7049389 + NUC + Pegylated-Interferon (Peg-IFN) for 48 weeks. RO7049389 will be administered at a dose determined from Part 2. NUC and Peg-IFN therapy will be administered per local label or guidelines.


Treatment: Drugs: Midazolam
Single dose of 100 mcg midazolam solution will be administered orally, before (Day -1) and after (Day 14) the treatment with RO7049389 or matching placebo

Other interventions: Placebo
Placebo matching to RO7049389 will be administered as per schedule described in individual arm.

Treatment: Drugs: RO7049389
RO7049389 will be administered as per schedule described in individual arm.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Percentage of Participants With Adverse Events
Timepoint [1] 0 0
Up to Day 29 (Part 1a), Day 44 (Part 1b), Day 42 (Part 1c)
Primary outcome [2] 0 0
Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389
Timepoint [2] 0 0
Up to 28 days
Primary outcome [3] 0 0
Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389
Timepoint [3] 0 0
Up to 28 days
Primary outcome [4] 0 0
Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389
Timepoint [4] 0 0
Up to 28 days
Primary outcome [5] 0 0
Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389
Timepoint [5] 0 0
Up to 28 days
Primary outcome [6] 0 0
Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389
Timepoint [6] 0 0
Up to Day 28
Primary outcome [7] 0 0
Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389
Timepoint [7] 0 0
Up to Day 28
Primary outcome [8] 0 0
Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389
Timepoint [8] 0 0
Up to Day 28
Primary outcome [9] 0 0
Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389
Timepoint [9] 0 0
Up to Day 28
Primary outcome [10] 0 0
Part 2: Percentage of Participants With Adverse Events
Timepoint [10] 0 0
Up to Day 112
Primary outcome [11] 0 0
Part 2: Quantitative Plasma HBV DNA Level
Timepoint [11] 0 0
Baseline - Day 112
Primary outcome [12] 0 0
Part 3: Proportion of Patients Achieving Functional Cure
Timepoint [12] 0 0
Every 2-4 weeks from Baseline through Week 72
Secondary outcome [1] 0 0
Part 1b: Food Effect on Cmax of RO7049389
Timepoint [1] 0 0
Day 16
Secondary outcome [2] 0 0
Part 1b: Food Effect on AUCinf of RO7049389
Timepoint [2] 0 0
Day 16
Secondary outcome [3] 0 0
Part 1c: Cmax of Midazolam
Timepoint [3] 0 0
Up to Day 14
Secondary outcome [4] 0 0
Part 1c: AUCinf of Midazolam
Timepoint [4] 0 0
Up to Day 14
Secondary outcome [5] 0 0
Part 1c: Tmax of RO7049389
Timepoint [5] 0 0
Up to Day 14
Secondary outcome [6] 0 0
Part 1c: Cmax of RO7049389
Timepoint [6] 0 0
Up to Day 14
Secondary outcome [7] 0 0
Part 1c: AUC0-12hr of RO7049389
Timepoint [7] 0 0
Up to Day 14
Secondary outcome [8] 0 0
Part 1c: CLr of RO7049389
Timepoint [8] 0 0
Up to Day 14
Secondary outcome [9] 0 0
Part 1c: Accumulation Ratio of RO7049389
Timepoint [9] 0 0
Day 1, Day 14
Secondary outcome [10] 0 0
Part 1c: T1/2 of RO7049389
Timepoint [10] 0 0
Up to Day 14
Secondary outcome [11] 0 0
Part 1c: Ae of RO7049389
Timepoint [11] 0 0
Up to Day 14
Secondary outcome [12] 0 0
Part 1c: Ctrough of RO7049389
Timepoint [12] 0 0
Up to Day 14
Secondary outcome [13] 0 0
Part 2: HBV DNA < Lower Limit of Quantification (LLOQ)
Timepoint [13] 0 0
Baseline - Day 112/Follow-up Day 84
Secondary outcome [14] 0 0
Part 2: Tmax of RO7049389
Timepoint [14] 0 0
Up to Day 28
Secondary outcome [15] 0 0
Part 2: Cmax of RO7049389
Timepoint [15] 0 0
Up to Day 28
Secondary outcome [16] 0 0
Part 2: AUCtau of RO7049389
Timepoint [16] 0 0
Up to Day 28
Secondary outcome [17] 0 0
Part 2: Accumulation Ratio of RO7049389
Timepoint [17] 0 0
Day 1, Day 28
Secondary outcome [18] 0 0
Part 2: T1/2 of RO7049389
Timepoint [18] 0 0
Up to Day 28
Secondary outcome [19] 0 0
Part 2: Ctrough of RO7049389
Timepoint [19] 0 0
Up to Day 28
Secondary outcome [20] 0 0
Part 3: Percentage of Participants With AEs
Timepoint [20] 0 0
72 weeks
Secondary outcome [21] 0 0
Part 3: Hepatitis B Surface Antigen (HBsAg) Level
Timepoint [21] 0 0
Baseline - Week 72
Secondary outcome [22] 0 0
Part 3: Hepatitis B e-Antigen (HBeAg) Levels
Timepoint [22] 0 0
Baseline - Week 72
Secondary outcome [23] 0 0
Part 3: HBV RNA Level
Timepoint [23] 0 0
Baseline - Week 72
Secondary outcome [24] 0 0
Part 3: HBV Core-Related Antigen (HBcrAg) Levels
Timepoint [24] 0 0
Baseline - Week 72
Secondary outcome [25] 0 0
Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation
Timepoint [25] 0 0
Week 12 - Week 72
Secondary outcome [26] 0 0
Part 3: Percentage of Participants With Anti-Hepatitis B Core Antigen (HBc) Antibodies
Timepoint [26] 0 0
Up to Week 72
Secondary outcome [27] 0 0
Part 3: HBV DNA Level
Timepoint [27] 0 0
Baseline - Week 72
Secondary outcome [28] 0 0
Part 3: HBV DNA < Lower Limit of Quantification (LLOQ)
Timepoint [28] 0 0
Baseline - Week 72
Secondary outcome [29] 0 0
Part 3: Tmax of RO7049389
Timepoint [29] 0 0
Day 1 - Week 48
Secondary outcome [30] 0 0
Part 3: Cmax of RO7049389
Timepoint [30] 0 0
Day 1 - Week 48
Secondary outcome [31] 0 0
Part 3: AUCtau of RO7049389
Timepoint [31] 0 0
Day 1 - Week 48
Secondary outcome [32] 0 0
Part 3: T1/2 of RO7049389
Timepoint [32] 0 0
Day 1 - Week 48

Eligibility
Key inclusion criteria
Part 1- Healthy Volunteers only:

* Absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead Electrocardiogram (ECG), hematology, blood chemistry, serology and urinalysis
* A Body Mass Index (BMI) between 18 to 30 kilograms per square meter (kg/m^2) inclusive
* Female participants must be either surgically sterile or post-menopausal for at least one year
* For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Part 2- Chronic HBV-infected participants only:

* A BMI between 18 to 30 kg/m^2 inclusive
* Chronic Hepatitis B infection, defined as positive test for Hepatitis B surface antigen (HBsAg) for more than 6 months prior to randomization
* HBV DNA at screening greater than or equal to (>/=) 2 × 10^4 international units per milliliter (IU/mL) for Hepatitis B e antigen (HBeAg) positive participants, or >/=2 × 10^3 IU/mL for HBeAg-negative participants
* Liver biopsy, fibroscan or equivalent test obtained within the past 6 months demonstrating liver disease consistent with chronic HBV infection with absence of extensive bridging fibrosis and absence of cirrhosis
* For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
* For women of childbearing potential: agreement to remain abstinent or use non-hormonal contraceptive methods that result in a failure rate of less than (<)1 percent (%) per year during the treatment period and for at least 3 months after the last dose of study drug

Part 3- Chronic HBV Participants Only:

* A BMI between 18 to 32 kg/m^2 inclusive
* Chronic hepatitis B infection, defined as positive test for HBsAg or HBV DNA, or positive HBeAg, for more than 6 months prior to screening
* For Cohorts only enrolling NUC-suppressed CHB participants (e.g. POM Cohort A), participants must have been treated with a single NUC (entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate) for at least 12 months. Participants must be on the same NUC therapy for at least 3 months prior to screening
* For Cohorts only enrolling anti-HBV treatment-naive and immune-active participants (e.g. POM Cohort B and Cohort C), previous anti-HBV treatments <30 days in total, and did not receive any anti-HBV treatments within 3 months prior to the first study dose
* Liver biopsy, fibroscan, or equivalent test obtained within the past 6 months demonstrating liver disease consistent with chronic HBV infection with absence of extensive bridging fibrosis and absence of cirrhosis
* For men: agreement to remain abstinent or use contraceptive measures, and agree to refrain from donating sperm
* For women of childbearing potential: agreement to remain abstinent or to use two approved contraceptive methods during the study and for at least 6 months after the last dose of study drug
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Part 1- Healthy Volunteers only:

* History or symptoms of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis
* History of Gilbert's syndrome
* Participants who have had significant acute infection, e.g., influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks of dose administration
* Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies
* Any clinically significant concomitant diseases or condition that could interfere with, or treatment of which 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 test at screening of any of the following: Hepatitis A (HAV IgM Ab), Hepatitis B (HBsAg), Hepatitis C (HCV RNA or HCV Ab) or human immunodeficiency virus (HIV Ab)
* Acute narrow-angle glaucoma (for MAD-midazolam cohorts)

Part 2- Chronic HBV-infected participants only:

* History or other evidence of bleeding from esophageal varices
* Evidence of liver cirrhosis or decompensated liver disease such as ascites, esophageal or gastric varices, splenomegaly, nodular liver, jaundice, hepatic encephalopathy
* 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 steatohepatitis, etc.)
* Documented history or other evidence of metabolic liver disease within one year of randomization
* Positive test for hepatitis A (IgM anti-HAV), hepatitis C, hepatitis D, or human immunodeficiency virus
* History of or suspicion of hepatocellular carcinoma or alphafetoprotein >/= Upper limit of normal (ULN) at screening
* History of clinically significant gastrointestinal, cardiovascular, endocrine, renal, ocular, pulmonary, psychiatric or neurological disease
* History of organ transplantation
* Previous or concurrent HBV treatments in the past 6 months
* Significant acute infection (e.g., influenza, local infection) or any other clinically significant illness within 2 weeks of randomization

Part 3- Chronic Hepatitis B Participants Only:

* History or other evidence of bleeding from esophageal varices
* Evidence of liver cirrhosis or decompensated liver disease such as ascites, esophageal or gastric varices, splenomegaly, nodular liver, jaundice, or hepatic encephalopathy
* 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 statohepatitis, etc.)
* History of thyroid disease poorly controlled on prescribed medications or clinically relevant abnormal thyroid function tests
* Documented history or other evidence of metabolic liver disease within one year of screening
* Positive test for hepatitis A (IgM anti-HAV), hepatitis C, hepatitis D, HEV, or HIV
* Diagnosed or suspected hepatocellular carcinoma
* History of clinically significant gastrointestinal, cardiovascular, endocrine, renal, ocular, pulmonary, psychiatric, or neurological disease
* History of organ transplantation
* Significant acute infection (e.g. influenza, local infection) or any other clinically significant illness within 2 weeks of screening

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
14/12/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/03/2022
Sample size
Target
Accrual to date
Final
192
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Sofia
Country [2] 0 0
China
State/province [2] 0 0
Guangzhou
Country [3] 0 0
China
State/province [3] 0 0
Shanghai City
Country [4] 0 0
China
State/province [4] 0 0
Shanghai
Country [5] 0 0
Hong Kong
State/province [5] 0 0
Hong Kong
Country [6] 0 0
Hong Kong
State/province [6] 0 0
Shatin, New Territories
Country [7] 0 0
New Zealand
State/province [7] 0 0
Auckland
Country [8] 0 0
New Zealand
State/province [8] 0 0
Grafton
Country [9] 0 0
Singapore
State/province [9] 0 0
Singapore
Country [10] 0 0
Taiwan
State/province [10] 0 0
Kaohsiung City
Country [11] 0 0
Taiwan
State/province [11] 0 0
Kaohsiung
Country [12] 0 0
Taiwan
State/province [12] 0 0
Taichung
Country [13] 0 0
Taiwan
State/province [13] 0 0
Tainan
Country [14] 0 0
Taiwan
State/province [14] 0 0
Taipei City
Country [15] 0 0
Taiwan
State/province [15] 0 0
Taipei
Country [16] 0 0
Thailand
State/province [16] 0 0
Bangkok
Country [17] 0 0
Thailand
State/province [17] 0 0
Chiang Mai

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.

Results are available at https://clinicaltrials.gov/study/NCT02952924