Clinical trial NCT02604355: A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7020322 Following Oral Administration in Healthy Participants and Chronic Hepatitis B Patients
Official title: A Multiple-Center, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose and Multiple-Ascending Dose, Adaptive Parallel Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7020322 Following Oral Administration in Healthy Subjects and Chronic Hepatitis B Patients
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatitis B, Chronic
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-11-13
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a multiple-center, randomized, double-blind, placebo-controlled, single-ascending dose and multiple-ascending dose, adaptive parallel study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7020322 following oral administration in healthy participants and chronic hepatitis B patients.


Eligibility criteria: Inclusion Criteria:

Healthy Participants' Inclusion Criteria:

* A Body Mass Index (BMI) between 18 to 30 kg/m\^2, inclusive, and a body weight of at least 50 kg
* Males must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm during the study
* Women should be of non-childbearing potential
* Able to comply with study restrictions
* Non-smoker (nor tobacco-containing products) for at least 90 days prior to dosing on Day 1 and agreeing not to smoke during the study

Chronic Hepatitis B-Infected Participants' Inclusion Criteria:

* Chronic hepatitis B infection
* A BMI between 18 to 32 kg/m\^2, inclusive
* Positive test for HBsAg for more than 6 months prior to randomization
* On entecavir or tenofovir treatment for at least 6 months prior to randomization and remaining on stable treatment during the study
* Liver biopsy, fibroscan® or equivalent test obtained within the past 6 months demonstrating liver disease consistent with chronic hepatitis B (HBV) infection without evidence of bridging fibrosis or cirrhosis
* Males must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm during the study
* Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use non-hormonal contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least until the end of the follow-up period

Exclusion Criteria:

Healthy Participants' Exclusion Criteria:

* Women who are lactating
* Any suspicion or history of alcohol and/or other substance abuse or dependence in the past 6 months
* Positive urine drug and alcohol screen (barbiturates, benzodiazepines, methadone, amphetamines, methamphetamines, opiates, cocaine, cannabinoids, and alcohol), or positive cotinine test at Day -1
* Positive result on HBV, hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 and 2
* A personal history of unexplained blackouts or faints, or known risk factors for Torsade de Pointes
* Clinically significant abnormalities (as judged by the Investigator) in the physical examination and in the laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis) at screening and on Day -1
* Participation in an investigational drug or device study within 90 days prior to screening or 5 times the half-life of the investigational drug (whichever is longer)
* Donation of blood over 500 mL within three months prior to screening
* Concomitant disease or condition (including allergic reactions against any drug, or multiple allergies) 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 healthy participant in this study

Chronic Hepatitis B-Infected Participants' Exclusion Criteria:

* Women who are pregnant (positive pregnancy test) or lactating
* History or other evidence of bleeding from esophageal varices
* Decompensated liver disease
* History or other evidence of a medical condition associated with chronic liver disease other than HBV infection
* Documented history or other evidence of metabolic liver disease within one year of randomization
* Positive test for hepatitis A (IgM anti-HAV), hepatitis C, or HIV
* Documented history of infection with hepatitis D virus
* Expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study, with the exception of oral therapy for herpes simplex virus (HSV) I or HSV II
* History of immunologically-mediated disease

Primary outcomes:
measure: Number of participants with adverse events
timeFrame: Up to 8 weeks
measure: Intensity of adverse events
timeFrame: Up to 8 weeks
measure: Number of participants with clinically significant laboratory abnormalities
timeFrame: Up to 8 weeks
measure: Number of participants with clinically significant electrocardiogram (ECG) abnormalities
timeFrame: Up to 8 weeks
measure: Number of participants with clinically significant vital signs abnormalities
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of RO7020322
timeFrame: Up to 18 days
measure: Time from dosing to Cmax (Tmax) of RO7020322
timeFrame: Up to 18 days
measure: Trough plasma concentrations (Ctrough) of RO7020322
timeFrame: Up to 18 days
measure: Area under the plasma concentration-time curve between time zero (pre-dose) and the time of the last quantifiable concentration (AUClast) of RO7020322
timeFrame: Up to 18 days
measure: Area under the plasma concentration-time curve between time zero (pre-dose) extrapolated to infinity (AUC0-Inf) of RO7020322
timeFrame: Up to 18 days
measure: Apparent clearance (CL/F) of RO7020322
timeFrame: Up to 18 days
measure: Apparent volume (V/F) of RO7020322
timeFrame: Up to 18 days
measure: Apparent terminal phase half-life (t1/2) of RO7020322
timeFrame: Up to 18 days
measure: Area under the plasma concentration-time curve (AUC0-t,ss) of RO7020322 at steady state
timeFrame: Up to 18 days
measure: Area under the plasma concentration-time curve (AUC0-t) of RO7020322 on Day 1
timeFrame: Up to 18 days
measure: Plasma concentration of hepatitis B surface antigen (HBsAg)
timeFrame: Up to 8 weeks
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Grafton
country: New Zealand
facility: Auckland Clinical Studies Limited
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: