A PHASE I, SPONSOR-OPEN, INVESTIGATORBLINDED,SUBJECT-BLINDED, MULTI-CENTER, PLACEBO-CONTROLLED STUDY TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF ORAL ADMINISTRATION OF RO7020531: (1). SINGLE AND MULTIPLE ASCENDING DOSES IN HEALTHY MALE AND FEMALE SUBJECTS; (2). 6-WEEK TREATMENT OF VIROLOGICALLY SUPPRESSED PATIENTS WITH CHRONIC HEPATITIS B VIRUS INFECTIO

Completed

• Conditions: Chronic Hepatitis B virus infection; 10019654; 10047438

• Registration Number: NL-OMON55546
• Lead Sponsor: Covance

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2022-01-29
• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 4

Inclusion Criteria

Patients must meet the following criteria for study entry:
1. Adult male and female patients, 18 to 65 years of age, inclusive.
2. Informed of, and willing and able to comply with, all of the protocol
requirements and the
investigational nature of the study, and have signed an informed consent form
(ICF) in accordance
with institutional and regulatory requirements.
3. A BMI between 21 to 32 kg/m2, inclusive. Males must be above 55 kg and
females above 45 kg body weight.
4. Chronic hepatitis B infection (positive test for hepatitis B surface
antigen (HBsAg) for more
than 6 months prior to randomization).
5. HBsAg detectable at screening.
6. On treatment with tenofovir, entecavir, adefovir, or telbivudine, either
as single agents or
in combination, for at least 6 months. For Cohort 4: HBV treatment naïve or not
on any anti-HBV treatment for the past 6 monts.
7. HBV DNA < 90 IU/mL for at least 6 months prior to randomization; HBV DNA <
90
IU/mL at screening by Roche Cobas assay. For Cohort 4: HBV DNA at screening *2
x 104 IU/mL for HBeAg positive and * 2 x 103 IU/mL for HBeAg negative patients.
8. Alanine amino transferase (ALT) * 1.5 × upper limit of normal (ULN) during
the 6 months prior
to randomization confirmed by two measurements separated by at least 14 days
(one of the ALT measurements can be done at screening); ALT at screening * 1.5
× ULN. For Cohort 4: ALT and aspartate aminotransferase (AST) at screening and
Day -1 visit: *5 x ULN.
9. Screening laboratory values (including hematology, chemistry, urinalysis)
obtained up
to 28 days prior to first study treatment within acceptable range or judged to
be not clinically
significant by the Principal Investigator (PI) and Medical Monitor.
10. Aspartate aminotransferase (AST), Gamma glutamyl transpeptidase (GGT),
alkaline phosphatase
(ALP), albumin, total and direct bilirubin within normal range or judged to be
not clinically
significant by the Investigator and Medical Monitor at screening.
11. Negative ANA test, or positive with dilutions not greater than 1:40 and
with no associated
history or symptoms of potential connective tissue disease or other
immune-mediated diseases.
12. Liver biopsy, fibroscan* or equivalent elastography test obtained within 6
months prior to
randomization demonstrating liver disease consistent with chronic HBV infection
with absence of
cirrhosis and absence of extensive bridging fibrosis (cirrhosis or extensive
bridging fibrosis are
defined as * Metavir 3, recommended cutoff for fibroscan 8.5 kPa).
13. For women of childbearing potential: agreement to remain abstinent (refrain
from heterosexual
intercourse) or use two approved contraceptive methods, of which one must be a
barrier method and
the other should be an established non-barrier form of contraception with a
failure rate of < 1%
per year, during the treatment period and for at least one month after the last
dose of study drug.
a. A woman is considered to be of childbearing potential if she is
post-menarcheal, has not
reached a post-menopausal state (* 12 continuous months of amenorrhea with no
identified cause
other than menopause), and has not undergone surgical sterilization (removal of
ovaries and/or
uterus).
b. Examples of contraceptive methods with a failure rate

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from study
entry:
1. Pregnant (positive pregnancy test) or lactating women and male partners of
women who are
pregnant or lactating.
2. History of liver cirrhosis.
3. History or other evidence of bleeding from esophageal varices.
4. Decompensated liver disease (e.g., Child-Pugh Class B or C clinical
classification or clinical
evidence such as ascites or varices).
5. 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 steato-hepatitis, etc.).
6. Documented history or other evidence of metabolic liver disease within one
year of
randomization.
7. Positive test for Hepatitis A virus (IgM anti-HAV), Hepatitis C (HVC),
Hepatitis D virus, Hepatitis E virus (HEV), or human immunodeficiency virus
(HIV).
8. 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 type I (HSV I) or HSV II.
9. History of or suspicion of hepatocellular carcinoma or alpha fetoprotein *
13 ng/mL at
screening.
10. History of immunologically mediated disease (e.g., inflammatory bowel
disease,
idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic
anemia, scleroderma,
severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other
autoimmune disease).
11. History of clinically significant cardiovascular, endocrine, renal, ocular,
pulmonary or
neurological disease (as per Investigator*s judgment).
12. History of clinically significant GI disease including inflammatory bowel
disease, peptic ulcer
disease, GI hemorrhage.
13. History of clinically significant psychiatric disease, especially major
depression (significant
psychiatric disease is defined as treatment with an antidepressant medication
or a major
tranquilizer at therapeutic doses for major depression or psychosis,
respectively, or any history
of the following: a suicide attempt, hospitalization for psychiatric disease,
or a period of
disability due to a psychiatric disease).
14. Evidence of an active or suspected cancer or a history of malignancy, where
in the
Investigator*s opinion, there is a risk of recurrence
15. History of having received or currently receiving any systemic
anti-neoplastic (including
radiation) or immune-modulatory treatment (including systemic oral or inhaled
corticosteroids, IFN
or PEG-IFN) within the 8 weeks prior to the first dose of study drug or the
expectation that such
treatment will be needed at any time during the study. Eye drop-containing and
infrequent inhaled
corticosteroids are permissible up to 4 weeks prior to the first dose of study
drug.
16. History of organ transplantation.
17. Clinically significant thyroid disease; also, patients with clinically
significant elevated
TSH concentrations at screening.
18. Any confirmed clinically significant allergic reactions (anaphylaxis)
against any drug, or
multiple drug allergies (non-active hay fever is acceptable).
19. Clinically significant acute infection (e.g., influenza, lo

Study & Design

• Study Type: Interventional
• Study Design: Not specified