A Multiple Ascending Dose Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Pharmacodynamics in Subjects with Chronic Hepatitis B Virus (HBV) Infectio
- Conditions
- Chronic Hepatitis B Virus (HBV) InfectionInfection - Studies of infection and infectious agentsOral and Gastrointestinal - Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
- Registration Number
- ACTRN12623000708651
- Lead Sponsor
- Argo Biopharma Australia Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 32
PART B Inclusion Criteria:
Subjects must meet all the following criteria to be eligible to participate in the study.
1. Must have given written informed consent and be able to comply with all study requirements.
2. Males or females aged 18 to 65 aged years, inclusive, at the time of informed consent.
3. BMI (more than and equal to) 18 and (less than equal to) 32 kg/m2 with body weight >50 kg at screening.
4. Chronic HBV infection as defined by a positive serum HBsAg for (more than equal to) 6 months at screening.
5. On nucleotide/nucleoside analogs (NUC) therapy for at least 6 months without an interruption of 7 or more consecutive days at screening (Not applicable for NUC naive subjects)
6. NUC naive at screening (Only for NUC naive subjects).
7. HBSAg >50 IU/mL at screening.
8. HBV DNA <9o IU/mL at screening (Not applicable for NUC naive subjects).
9. Triplicate 12-lead electrocardiogram(ECG) with normal limits or without clinically significant abnormalities· at screening, as determined by the Investigator.
10. Female subjects must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal. Women of child-bearing potential, defined as all women
physiologically capable of becoming pregnant. with male partners, can participate if they are using highly effective methods of contraception· from 28 days prior to screening until go days following last administration of the study drug and use contraceptive as per study protocol..
11. Male subjects with female partners of child-bearing potential must agree to use acceptable methods of contraception from study drug administration until go days following last administration of the study drug and use contraceptives as per study protocol.
PART B Exclusion Criteria:
1. Any clinically significant chronic medical condition other than chronic HBV infection or clinically significant abnormality in laboratory parameters not related to chronic HBV infection that. in the opinion of the Investigator, makes the participant unsuitable for participation in the study.
2. Any clinically significant acute condition such as fever (>38 degree celsius) or acute respiratory illness within 7 days of study drug administration.
3. Significant liver fibrosis or cirrhosis as defined by having either a FibroScan result of > 8.5kPa at screening or a liver biopsy within 1 year with Metavir F3 fibrosis or F4 cirrhosis.
4. Subject has the following laboratory parameters at screening (by local laboratory):
- INR > 1.2 x ULN
- serum ALT or AST > 2 ULN
Study laboratory tests may be repeated once (eg, for values thought to be erroneous).
5. Active infection with HCV, hepatitis Delta virus (HDV), or HIV at screening.
6. Use of an investigational agent or device within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug.
7. Used prescription drugs within 14 days or 5 half-lives (whichever is longer) before study drug administration except for a stable dose of: medication to treat hypertension, inhaler or nebulizer to treat asthma, hormone replacement therapy, antihistamines, and contraceptive therapy. Hypertension must be well controlled on no more than 2 medications or 1 medication with two active components for >6 months. Asthma must be well controlled, requiring, on average, use of a rescue bronchodilator no more than twice per week.
8. Over-the-counter medications, excluding routine vitamins and paracetamol, within 7 days or 5 half-lives (whichever is longer) before study drug administration, unless determined by the Investigator and Sponsor to be not clinically relevant. and unlikely to interfere with study conduct. and unlikely to interfere with study conduct.
9. Consume more than 7 units of alcohol per week within one month before screening (unit: 1 glass of wine [125 mL = 1 measure of spirits [30 mL = one-half pint of beer [284 mL]). Alcohol is limited to no more than 1 unit per day for the duration of the study.
10. History or clinical evidence of alcohol or drug abuse, within the 12 months before screening or a positive test for alcohol or drugs of abuse at screening.
11. Calculated creatinine clearance (less than equal to) 60 ml/min (Cockcroft-Gault equation).
12. History of chronic liver disease from any cause other than chronic HBV infection.
13. Diagnosed or suspected hepatocellular carcinoma.
14. History of hepatic decompensation, including ascites, hepatic encephalopathy and/or esophageal or gastric varices
15. Currently taking, or has taken within 12 months of screening, any interferon-containing therapy.
16. History of allergic reaction to a siRNA or GalNAc.
17. Have received vaccination with a live vaccine (except for influenza vaccine) during the past 4 weeks before Screening or have the intention to receive a live vaccine during the study period. NOTE: Receipt of
inactivated vaccines (inactivated influenza vaccines and approved COVID-19 vaccines) is not considered exclusionary if received at least 7 days prior to study drug administration.
18. Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrollment or could interfere with the subject's participation in or completion of the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method