A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7020322 Following Oral Administration in Healthy Participants and Chronic Hepatitis B Patients

Phase 1

Terminated

• Conditions: Hepatitis B, Chronic
• Interventions: Other: Matching Placebo; Drug: RO7020322

• Registration Number: NCT02604355
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-11-10
• Study First Submitted QC: 2015-11-10
• Study First Posted: 2015-11-13
• Study Start: 2015-11-28
• Primary Completion: 2016-05-09
• Study Completion: 2016-05-09
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-23
• Last Update Posted: 2017-05-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 49

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Participants (Single-Ascending Dosing)	Matching Placebo	-
Healthy Participants (Study of Food Effect)	Matching Placebo	-
Healthy Participants (Multiple-Ascending Dosing)	Matching Placebo	-
Participants with Chronic Hepatitis B (Proof of mechanism)	Matching Placebo	-
Healthy Participants (Single-Ascending Dosing)	RO7020322	-
Healthy Participants (Study of Food Effect)	RO7020322	-
Healthy Participants (Multiple-Ascending Dosing)	RO7020322	-
Participants with Chronic Hepatitis B (Proof of mechanism)	RO7020322	-

Primary Outcome Measures

Name	Time	Method
Number of participants with clinically significant laboratory abnormalities	Up to 8 weeks
Number of participants with adverse events	Up to 8 weeks
Number of participants with clinically significant electrocardiogram (ECG) abnormalities	Up to 8 weeks
Intensity of adverse events	Up to 8 weeks
Number of participants with clinically significant vital signs abnormalities	Up to 8 weeks

Secondary Outcome Measures

Name	Time	Method
Area under the plasma concentration-time curve between time zero (pre-dose) extrapolated to infinity (AUC0-Inf) of RO7020322	Up to 18 days
Apparent clearance (CL/F) of RO7020322	Up to 18 days
Apparent volume (V/F) of RO7020322	Up to 18 days
Area under the plasma concentration-time curve (AUC0-t,ss) of RO7020322 at steady state	Up to 18 days
Apparent terminal phase half-life (t1/2) of RO7020322	Up to 18 days
Area under the plasma concentration-time curve (AUC0-t) of RO7020322 on Day 1	Up to 18 days
Plasma concentration of hepatitis B surface antigen (HBsAg)	Up to 8 weeks
Time from dosing to Cmax (Tmax) of RO7020322	Up to 18 days
Trough plasma concentrations (Ctrough) of RO7020322	Up to 18 days
Area under the plasma concentration-time curve between time zero (pre-dose) and the time of the last quantifiable concentration (AUClast) of RO7020322	Up to 18 days
Maximum observed plasma concentration (Cmax) of RO7020322	Up to 18 days

Trial Locations

Locations (4)

Auckland Clinical Studies Limited; 🇳🇿 Grafton, New Zealand

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Tauranga Hospital; 🇳🇿 Tauranga, New Zealand

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong