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

NCT02604355 | Terminated Phase 1

• 1 other identifier: BP29948
• Study Type: interventional
• Target: 49
• Locations: 3 countries
• Sites: 4

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.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (5)

• Number of participants with adverse events

  Up to 8 weeks

• Intensity of adverse events

  Up to 8 weeks

• Number of participants with clinically significant laboratory abnormalities

  Up to 8 weeks

• Number of participants with clinically significant electrocardiogram (ECG) abnormalities

  Up to 8 weeks

• Number of participants with clinically significant vital signs abnormalities

  Up to 8 weeks

Secondary Outcomes (11)

• Maximum observed plasma concentration (Cmax) of RO7020322

  Up to 18 days

• 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

• Area under the plasma concentration-time curve between time zero (pre-dose) extrapolated to infinity (AUC0-Inf) of RO7020322

  Up to 18 days

Study Arms (4)

Healthy Participants (Multiple-Ascending Dosing)

EXPERIMENTAL

Other: Matching Placebo; Drug: RO7020322

Healthy Participants (Single-Ascending Dosing)

EXPERIMENTAL

Other: Matching Placebo; Drug: RO7020322

Healthy Participants (Study of Food Effect)

EXPERIMENTAL

Other: Matching Placebo; Drug: RO7020322

Participants with Chronic Hepatitis B (Proof of mechanism)

EXPERIMENTAL

Other: Matching Placebo; Drug: RO7020322

Interventions

Matching Placebo OTHER

Oral dosing with placebo capsules to match RO7020322.

Healthy Participants (Multiple-Ascending Dosing); Healthy Participants (Single-Ascending Dosing); Healthy Participants (Study of Food Effect); Participants with Chronic Hepatitis B (Proof of mechanism)

RO7020322 DRUG

Adaptive oral dosing with RO7020322 capsules, starting at 1 mg daily, with ascending or adjusted dosing based on the results of previous dosing.

Healthy Participants (Multiple-Ascending Dosing); Healthy Participants (Single-Ascending Dosing); Healthy Participants (Study of Food Effect); Participants with Chronic Hepatitis B (Proof of mechanism)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (4)

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Auckland Clinical Studies Limited

Grafton, 1010, New Zealand

Location

Tauranga Hospital

Tauranga, 3143, New Zealand

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2015
• First Posted: November 13, 2015
• Study Start: November 28, 2015
• Primary Completion: May 9, 2016
• Study Completion: May 9, 2016
• Last Updated: May 25, 2017

Record last verified: 2017-05

Locations

HK (1); TW (1); NZ (2)