Clincosm LogoSign in Get a demo

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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02952924
Collaborator
(none)
192
Enrollment
21
Locations
9
Arms
63
Actual Duration (Months)
9.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a multicenter, three-part study. Parts 1 and 2 are randomized, investigator- and participant-blinded, placebo-control, single-ascending dose (SAD) and multiple-ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RO7049389 following oral administration in healthy volunteers and chronic HBV infected participants. Part 3 is a non-randomized, non-controlled, open-label part to assess the efficacy and safety of RO7049389 when administered in combination with standard-of-care therapies for up to 48 weeks in nucleos(t)ide (NUC)-suppressed and treatment-naive chronic hepatitis B (CHB) participants.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
192 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official 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.
Actual Study Start Date :
Dec 14, 2016
Actual Primary Completion Date :
Mar 16, 2022
Actual Study Completion Date :
Mar 16, 2022

Arms and Interventions

Arm Intervention/Treatment
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.

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

Drug: RO7049389
RO7049389 will be administered as per schedule described in individual arm.
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.

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

Drug: 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

Drug: RO7049389
RO7049389 will be administered as per schedule described in individual arm.
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.

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

Drug: RO7049389
RO7049389 will be administered as per schedule described in individual arm.
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.

Drug: RO7049389
RO7049389 will be administered as per schedule described in individual arm.
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.

Drug: RO7049389
RO7049389 will be administered as per schedule described in individual arm.
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.

Drug: RO7049389
RO7049389 will be administered as per schedule described in individual arm.

Outcome Measures

Primary Outcome Measures

  1. Part 1: Percentage of Participants With Adverse Events [From randomization up to Day 44]

  2. Part 2: Percentage of Participants With Adverse Events [From randomization up to Day 56]

  3. Part 2: HBV DNA Level [Baseline; Days 8, 15, 22, 28, 35, 56, 84, and 112]

  4. Part 1c- MAD Cohort: Area Under the Plasma Concentration Versus Time Curve for a Dosing Interval (AUC0-tau) of RO7049389 and Metabolites [Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose]

  5. Part 1c- MAD Cohort: Plasma Trough Concentration (Ctrough) of RO7049389 and Metabolites [Pre-dose (0 hr before morning dose) on Days 2, 3, 4, 5, 7]

  6. Part 1c- MAD Cohort: Apparent Terminal t1/2 of RO7049389 and Metabolites [Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose]

  7. Part 1c- MAD Cohort: Accumulation Index of RO7049389 and Metabolites [Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose]

  8. Part 1c- MAD Cohort: Ae of RO7049389 and Metabolites [Pre-dose (0 hr), 0-4, 4-8, 8-12, 12-24 hours post morning dose on Days 1 and 14]

  9. Part 1c- MAD Cohort: CLR of RO7049389 and Metabolites [Pre-dose (0 hr), 0-4, 4-8, 8-12, 12-24 hours post morning dose on Days 1 and 14]

  10. Part 1a- SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 and Metabolites [Pre-dose (0 hour [hr]) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose]

  11. Part 1a- SAD Cohort: Time to Reach Cmax (Tmax) of RO7049389 and Metabolites [Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose]

  12. Part 1a- SAD Cohort: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUC0-last) of RO7049389 and Metabolites [Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose]

  13. Part 1a- SAD Cohort: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO7049389 and Metabolites [Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose]

  14. Part 1a- SAD Cohort: Apparent Terminal Half-life (t1/2) of RO7049389 and Metabolites [Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose]

  15. Part 1a- SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 and Metabolites [Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose]

  16. Part 1a-SAD Cohort- Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 and Metabolites [Pre-dose (0 hr) on Day 1; 0-4, 4-8, 8-12, 12-24, 24-48 hours post Day 1 dose]

  17. Part 1a- SAD Cohort: Renal Clearance (CLR) of RO7049389 and Metabolites [Pre-dose (0 hr) on Day 1; 0-4, 4-8, 8-12, 12-24, 24-48 hours post Day 1 dose]

  18. Part 1c- MAD Cohort: Cmax of RO7049389 and Metabolites [Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose]

  19. Part 1c- MAD Cohort: Tmax of RO7049389 and Metabolites [Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose]

  20. Part 3 HBV DNA Level [Every 2-4 weeks from Baseline through Week 72]

  21. Part 3: HBsAg Level [Every 2-4 weeks from baseline through week 72]

Secondary Outcome Measures

  1. Part 1b- Food-Effect SAD Cohort: Cmax of RO7049389 [Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose]

  2. Part 1b- Food-Effect SAD Cohort: Tmax of RO7049389 [Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose]

  3. Part 1b- Food-Effect SAD Cohort: AUC0-last of RO7049389 [Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose]

  4. Part 1b- Food-Effect SAD Cohort: AUC0-inf of RO7049389 [Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose]

  5. Part 1b- Food-Effect SAD Cohort: Apparent Terminal t1/2 of RO7049389 [Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose]

  6. Part 1b- Food-Effect SAD Cohort: Apparent CL/F of RO7049389 [Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose]

  7. Part 1c- MAD Cohort: Cmax of Midazolam [Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14]

  8. Part 1c- MAD Cohort: Tmax of Midazolam [Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14]

  9. Part 1c- MAD Cohort: AUC0-last of Midazolam [Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14]

  10. Part 1c- MAD Cohort: AUC0-inf of Midazolam [Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14]

  11. Part 1c- MAD Cohort: Area Under the Plasma Concentration Versus Time Curve up to 6 h Post-dose (AUC0-6h) of Midazolam [Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14]

  12. Part 1c- MAD Cohort: Apparent Terminal t1/2 of Midazolam [Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14]

  13. Part 1c- MAD Cohort: CL/F of Midazolam [Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14]

  14. Part 2: Cmax of RO7049389 [Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose]

  15. Part 2: Tmax of RO7049389 [Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose]

  16. Part 2: AUC0-tau of RO7049389 [Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose]

  17. Part 2: Ctrough of RO7049389 [Pre-morning dose (0 hr) on Days 2, 3, 4, 8, 15, 22]

  18. Part 2: Apparent t1/2 of RO7049389 [Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose]

  19. Part 2: Accumulation Index of RO7049389 [Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose]

  20. Part 2: Anti-HBe Antibodies [Baseline; Days 8,15,22,28,35,56,84, and 112]

  21. Part 3: Cmax of RO7049389 and its Metabolites [Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)]

  22. Part 3: Tmax of RO7049389 and its metabolites [Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)]

  23. Part 3: AUC0-tau of RO7049389 and its metabolites [Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)]

  24. Part 3: Ctrough of RO7049389 and its metabolites [Pre-dose Days 14 and 28; thereafter predose every 28 days up to Week 48]

  25. Part 3: T1/2 of RO7049389 and its metabolites [Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)]

  26. Part 3: Accumulation Index of RO7049389 and its Metabolites [Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)]

  27. Part 3: Ctrough of Nucleos(t)ide Analogs (NUCs) [Pre-dose Days 14 (Cohort A and C only) and 28; thereafter predose every 28 days up to Week 48]

  28. Part 3: Hepatitis B e-Antigen (HBeAg) Levels [Every 2-4 weeks from Baseline through Week 72]

  29. Part 3: Anti-HBs Antibodies [Every 2-4 weeks from Baseline through Week 72]

  30. Part 3: Anti-HBe Antibodies [Every 2-4 weeks from Baseline through Week 72]

  31. Part 3: Anti-HBc antibodies [Every 2-4 weeks from Baseline through Week 72]

  32. Part 3: HBV RNA Level [Every 2-4 weeks from Baseline through Week 72]

  33. Part 3: HBV Core-Related Antigen Levels (HBcrAg) [Every 2-4 weeks from baseline through week 72]

  34. Part 3: Viral Resistance Monitoring [Every 2-4 weeks from baseline through week 72]

  35. Part 3 Percentage of Participants With Adverse Events [From randomization up to 72 Weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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 × 104 international units per milliliter (IU/mL) for Hepatitis B e antigen (HBeAg) positive participants, or >/=2 × 103 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

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Royal Brisbane and Women's Hospital Herston Queensland Australia 4029
2 Royal Melbourne Hospital Parkville Victoria Australia 3050
3 Acibadem City Clinic Tokuda Hospital Ead Sofia Bulgaria 1407
4 Nanfang Hospital, Southern Medical University Guangzhou China 510515
5 Huashan Hospital Affiliated to Fudan University Shanghai City China 200040
6 Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital) Shanghai China 200025
7 The University of Hong Kong; Queen Mary Hospital Hong Kong Hong Kong
8 Prince of Wales Hospital Shatin, New Territories Hong Kong
9 Middlemore Hospital Auckland New Zealand
10 Auckland Clinical Studies Limited Grafton New Zealand 1010
11 National University Health System Singapore Singapore 119228
12 Singapore General Hospital Singapore Singapore 169608
13 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung City Taiwan 807
14 Chang Gung Memorial Hospital - Kaohsiung Branch Kaohsiung Taiwan
15 Taichung Veterans Gen Hosp Taichung Taiwan 40705
16 National Cheng Kung University Hospital Tainan Taiwan 70457
17 Taipei Veterans General Hospital Taipei City Taiwan 112
18 Chang Gung Memorial Hospital - Linkou Branch Taipei Taiwan
19 King Chulalongkorn Memorial Hospital Bangkok Thailand 10330
20 Siriraj Hospital Bangkok Thailand 10700
21 Maharaj Nakorn Chiang Mai Hospital Chiang Mai Thailand 50200

Sponsors and Collaborators

  • Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02952924
Other Study ID Numbers:
  • YP39364
First Posted:
Nov 2, 2016
Last Update Posted:
Jul 8, 2022
Last Verified:
Jul 1, 2022
Additional relevant MeSH terms:
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Midazolam

Study Results

No Results Posted as of Jul 8, 2022