Hepatitis B, ChronicPhase 2NCT02391805
A Study of Treatment With RO6864018 in Virologically Suppressed Participants With Chronic Hepatitis B Virus (HBV) Infection
A Phase 2 study testing Entecavir, RO6864018 and Tenofovir in people with Hepatitis B, Chronic, run by Hoffmann-La Roche at 14 sites in 6 countries.
Trial summary
This randomized, multicenter, partially double-blind, placebo-controlled study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antiviral effects of treatment with RO6864018 in virologically suppressed participants with chronic HBV infection. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Entecavir, RO6864018 and Tenofovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 14 sitesin 6 countries
- Study dates
- 17 May 2015to 16 Oct 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic hepatitis B infection
- Positive test for HBsAg for more than 6 months prior to randomization
- HBsAg titer greater than or equal to (>/=) 250 international units per milliliter (IU/mL) at Screening
- Treatment with any nucleoside/nucleotide analogue for >/= 1 year with ongoing entecavir and/or tenofovir treatment at randomization and for at least 3 months prior to randomization
- HBV DNA less than (<) 90 IU/mL for at least the preceding 6 months
- HBeAg positive at randomization and for at least 6 months prior to randomization
Who cannot join
- Pregnant or lactating women
- Documented history of HBV genotype D
- History or other evidence of bleeding from esophageal varices
- History of decompensated liver disease, chronic liver disease other than HBV infection, or any evidence of metabolic liver disease
- Positive test for hepatitis A, hepatitis C, or human immunodeficiency virus (HIV)
- Documented history of hepatitis D infection
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- History of or suspicion of hepatocellular carcinoma
- History of immunologically mediated disease
- History of organ transplantation
- History of thyroid disease
- Significant acute infection
Trial locations and contacts
14 sites in 6 countries.
14 sites in 6 countries
Malaysia3 sites
Hospital Ampang
Ampang, 68000
Hospital Selayang; Medicine
Batu Caves, 68100
University Malaya Medical Center
Kuala Lumpur, 59100
South Korea3 sites
Seoul National University Hospital
Seoul, 03080
Severance Hospital, Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Taiwan3 sites
Kaohsiung Medical Uni Chung-Ho Memorial Hospital; Dept of Internal Medicine
Kaohsiung City, 807
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 112
Hong Kong2 sites
Queen Mary Hospital
Hong Kong
Prince of Wales Hospital; Special Medical Clinic
N.T.
New Zealand2 sites
Auckland Clinical Studies Limited
Grafton, 1010
Waikato Hospital
Hamilton, 3248
About this study
Official title: A Multiple-Center, Randomized, Partially Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antiviral Effects of 12-Week Treatment With RO6864018 in Virologically Suppressed Patients With Chronic Hepatitis B Virus Infection
This randomized, multicenter, partially double-blind, placebo-controlled study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antiviral effects of treatment with RO6864018 in virologically suppressed participants with chronic HBV infection.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Entecavir, Placebo, RO6864018, Tenofovir
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntecavirDrug
Entecavir will be administered as per local labeling.
PlaceboDrug
Participants will be administered PO placebo capsules matched to RO6864018, either QOD or QWk for 12 weeks of treatment.
RO6864018Drug
Participants will be administered RO6864018 as 200-mg PO capsules at a dose of 800 mg or 1200 mg, either QOD or QWk for 12 weeks of treatment.
TenofovirDrug
Tenofovir will be administered as per local labeling.
| Study group | Role | What they receive |
|---|---|---|
| Placebo, Every Other Day (QOD) | Placebo comparator | Placebo orally (PO) QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician Receives: Drug: Entecavir; Drug: Placebo; Drug: Tenofovir |
| Placebo, Once a Week (QWk) | Placebo comparator | Placebo PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician Receives: Drug: Entecavir; Drug: Placebo; Drug: Tenofovir |
| RO6864018, 1200 milligrams (mg) QOD | Experimental | RO6864018 1200 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician Receives: Drug: Entecavir; Drug: RO6864018; Drug: Tenofovir |
| RO6864018, 1200 mg QWk | Experimental | RO6864018 1200 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician Receives: Drug: Entecavir; Drug: RO6864018; Drug: Tenofovir |
| RO6864018, 800 mg QOD | Experimental | RO6864018 800 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician Receives: Drug: Entecavir; Drug: RO6864018; Drug: Tenofovir |
| RO6864018, 800 mg QWk | Experimental | RO6864018 800 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician Receives: Drug: Entecavir; Drug: RO6864018; Drug: Tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety: Percentage of Participants with Adverse Events
Measured: Baseline up to approximately 36 weeks
Secondary outcomes (47)
Pharmacodynamics: Peripheral Blood Levels of Interferon (IFN)-Alpha in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IFN-Alpha in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IFN-Gamma-Induced Protein (IP)-10 in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IP-10 in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Quantitative HBV Deoxyribonucleic Acid (DNA) Level in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up; and at any point that breakthrough occurs (up to 36 weeks)
Efficacy: Quantitative HBV DNA Level in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up; and at any point that breakthrough occurs (up to 36 weeks)
Efficacy: Quantitative Hepatitis B Surface Antigen (HBsAg) Level in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Quantitative HBsAg Level in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Loss of HBsAg in QOD Dosing Cohorts
Measured: Baseline; on Day 7 of Week 12; then at Week 36 during follow-up
Efficacy: Percentage of Participants with Loss of HBsAg in QWk Dosing Cohorts
Measured: Baseline; on Day 7 of Week 12; then at Week 36 during follow-up
Efficacy: Percentage of Participants with Loss of Hepatitis B Envelope Antigen (HBeAg) in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Loss of HBeAg in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with HBsAg Seroconversion in QOD Dosing Cohorts
HBsAg Seroconversion = antibody to HBsAg (Anti-HBs) Positive Status and Loss of HBsAg
Measured: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Week 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with HBsAg Seroconversion in QWk Dosing Cohorts
HBsAg Seroconversion = anti-HBs Positive Status and Loss of HBsAg
Measured: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with HBeAg Seroconversion in QOD Dosing Cohorts
HBeAg Seroconversion = antibody to HBeAg (anti-HBe) Positive Status and Loss of HBeAg
Measured: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Week 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with HBeAg Seroconversion in QWk Dosing Cohorts
HBeAg Seroconversion = anti-HBe Positive Status and Loss of HBeAg
Measured: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of RO6864018 Metabolite in QOD Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: Cmax of RO6864018 Metabolite in QWk Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of RO6864018 Metabolite in QOD Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: Tmax of RO6864018 Metabolite in QWk Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of RO6864018 Metabolite in QOD Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: AUCinf of RO6864018 Metabolite in QWk Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of RO6864018 Metabolite in QOD Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: AUClast of RO6864018 Metabolite in QWk Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: Half-life (t1/2) of RO6864018 Metabolite in QOD Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: T1/2 of RO6864018 Metabolite in QWk Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacodynamics: Peripheral Blood Levels of Neopterin in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of Neopterin in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of Tumor Necrosis Factor (TNF)-Alpha in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of TNF-alpha in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of Interleukin (IL)-6 in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-6 in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-10 in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-10 in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-12p40 in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-12p40 in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Development of Anti-HBe in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Development of Anti-HBe in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Development of Anti-HBs in QOD Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Development of Anti-HBs in QWk Dosing Cohorts
Measured: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Transcriptional Responses as Measured by messenger ribonucleic acid (mRNA) Levels for QWk Cohorts
Measured: QWk: Baseline; pre-dose (0 hours) and post-dose (6 and 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12, and Day 7 of Week 12; then Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Transcriptional Responses as Measured by messenger ribonucleic acid (mRNA) Levels for QOD Cohorts
Measured: Baseline; pre-dose; post-dose (6 and 24 hours) on Days 1, 3, and 7 for Week 1, Day 1 of Weeks 3, 5, 7, Day 6 of Week 12; then Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Percentage of T Cells, B Cells, and NK Cells (TBNK)
Measured: For QOD and QWk Cohorts: Baseline; pre-dose (0 hours) on Day 1 of Weeks 1, 2, 5; then Weeks 20, 28, 36 during follow-up
Pharmacodynamics: Percentage of Myeloid Cells
Measured: For QOD and QWk Cohorts: Baseline; pre-dose (0 hours) on Day 1 of Weeks 1, 2, 5; then Weeks 20, 28, 36 during follow-up
Pharmacodynamics: Percentage of Plasmacytoid Dendritic Cells
Measured: For QOD and QWk Cohorts: Baseline; pre-dose (0 hours) on Day 1 of Weeks 1, 2, 5; then Weeks 20, 28, 36 during follow-up
Pharmacokinetics: Cmax of Entecavir in QWk Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: AUCinf of Entecavir in QWk Dosing Cohorts
Measured: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2015 (estimated)
- Study start17 May 2015
- Primary completion16 Oct 2017
- Study completion16 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02391805
- Sponsor's protocol ID
- NP28938
- Status last verified
- Jun 2018
- First submitted
- 6 Mar 2015
- Last updated
- 6 Jun 2018
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multiple-Center, Randomized, Partially Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antiviral Effects of 12-Week Treatment With RO6864018 in Virologically Suppressed Patients With Chronic Hepatitis B Virus Infection
- ClinicalTrials.gov ID
- NCT02391805
- Acronym / sponsor ID
- NP28938
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 17 May 2015 (actual)
- Primary completion
- 16 Oct 2017 (actual)
- Study completion
- 16 Oct 2017 (actual)
- First posted
- 18 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized, multicenter, partially double-blind, placebo-controlled study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antiviral effects of treatment with RO6864018 in virologically suppressed participants with chronic HBV infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Placebo, Every Other Day (QOD) | Placebo comparator | Drug: Entecavir, Drug: Placebo, Drug: TenofovirPlacebo orally (PO) QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician |
| Placebo, Once a Week (QWk) | Placebo comparator | Drug: Entecavir, Drug: Placebo, Drug: TenofovirPlacebo PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician |
| RO6864018, 1200 milligrams (mg) QOD | Experimental | Drug: Entecavir, Drug: RO6864018, Drug: TenofovirRO6864018 1200 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician |
| RO6864018, 1200 mg QWk | Experimental | Drug: Entecavir, Drug: RO6864018, Drug: TenofovirRO6864018 1200 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician |
| RO6864018, 800 mg QOD | Experimental | Drug: Entecavir, Drug: RO6864018, Drug: TenofovirRO6864018 800 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician |
| RO6864018, 800 mg QWk | Experimental | Drug: Entecavir, Drug: RO6864018, Drug: TenofovirRO6864018 800 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Chronic hepatitis B infection
- Positive test for HBsAg for more than 6 months prior to randomization
- HBsAg titer greater than or equal to (>/=) 250 international units per milliliter (IU/mL) at Screening
- Treatment with any nucleoside/nucleotide analogue for >/= 1 year with ongoing entecavir and/or tenofovir treatment at randomization and for at least 3 months prior to randomization
- HBV DNA less than (<) 90 IU/mL for at least the preceding 6 months
Key exclusion criteria (11 listed)
- Pregnant or lactating women
- Documented history of HBV genotype D
- History or other evidence of bleeding from esophageal varices
- History of decompensated liver disease, chronic liver disease other than HBV infection, or any evidence of metabolic liver disease
- Positive test for hepatitis A, hepatitis C, or human immunodeficiency virus (HIV)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntecavirEntecavir will be administered as per local labeling. | Drug | Placebo, Every Other Day (QOD), Placebo, Once a Week (QWk), RO6864018, 1200 mg QWk, RO6864018, 1200 milligrams (mg) QOD, RO6864018, 800 mg QOD, RO6864018, 800 mg QWk |
| PlaceboParticipants will be administered PO placebo capsules matched to RO6864018, either QOD or QWk for 12 weeks of treatment. | Drug | Placebo, Every Other Day (QOD), Placebo, Once a Week (QWk) |
| RO6864018Participants will be administered RO6864018 as 200-mg PO capsules at a dose of 800 mg or 1200 mg, either QOD or QWk for 12 weeks of treatment. | Drug | RO6864018, 1200 mg QWk, RO6864018, 1200 milligrams (mg) QOD, RO6864018, 800 mg QOD, RO6864018, 800 mg QWk |
| TenofovirTenofovir will be administered as per local labeling. | Drug | Placebo, Every Other Day (QOD), Placebo, Once a Week (QWk), RO6864018, 1200 mg QWk, RO6864018, 1200 milligrams (mg) QOD, RO6864018, 800 mg QOD, RO6864018, 800 mg QWk |
Primary outcome
Safety: Percentage of Participants with Adverse Events
Time frame: Baseline up to approximately 36 weeks
47 secondary outcomes
Pharmacodynamics: Peripheral Blood Levels of Interferon (IFN)-Alpha in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IFN-Alpha in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IFN-Gamma-Induced Protein (IP)-10 in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IP-10 in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Quantitative HBV Deoxyribonucleic Acid (DNA) Level in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up; and at any point that breakthrough occurs (up to 36 weeks)
Efficacy: Quantitative HBV DNA Level in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up; and at any point that breakthrough occurs (up to 36 weeks)
Efficacy: Quantitative Hepatitis B Surface Antigen (HBsAg) Level in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Quantitative HBsAg Level in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Loss of HBsAg in QOD Dosing Cohorts
Time frame: Baseline; on Day 7 of Week 12; then at Week 36 during follow-up
Efficacy: Percentage of Participants with Loss of HBsAg in QWk Dosing Cohorts
Time frame: Baseline; on Day 7 of Week 12; then at Week 36 during follow-up
Efficacy: Percentage of Participants with Loss of Hepatitis B Envelope Antigen (HBeAg) in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Loss of HBeAg in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with HBsAg Seroconversion in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Week 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with HBsAg Seroconversion in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with HBeAg Seroconversion in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Week 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with HBeAg Seroconversion in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of RO6864018 Metabolite in QOD Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: Cmax of RO6864018 Metabolite in QWk Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of RO6864018 Metabolite in QOD Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: Tmax of RO6864018 Metabolite in QWk Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of RO6864018 Metabolite in QOD Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: AUCinf of RO6864018 Metabolite in QWk Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of RO6864018 Metabolite in QOD Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: AUClast of RO6864018 Metabolite in QWk Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacokinetics: Half-life (t1/2) of RO6864018 Metabolite in QOD Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Pharmacokinetics: T1/2 of RO6864018 Metabolite in QWk Dosing Cohorts
Time frame: Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Pharmacodynamics: Peripheral Blood Levels of Neopterin in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of Neopterin in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of Tumor Necrosis Factor (TNF)-Alpha in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of TNF-alpha in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of Interleukin (IL)-6 in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-6 in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-10 in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-10 in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-12p40 in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Pharmacodynamics: Peripheral Blood Levels of IL-12p40 in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Development of Anti-HBe in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Development of Anti-HBe in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Development of Anti-HBs in QOD Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Efficacy: Percentage of Participants with Development of Anti-HBs in QWk Dosing Cohorts
Time frame: Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
14 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Entecavir, RO6864018 and Tenofovir in people with Hepatitis B, Chronic, run by Hoffmann-La Roche at 14 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Malaysia, South Korea, Taiwan, Hong Kong, New Zealand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety: Percentage of Participants with Adverse Events (time frame: Baseline up to approximately 36 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2018; AzTrials last refreshed its copy on 8 Nov 2026.