ActivePhase 2ACTRN12623000708651

A Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Subjects with Chronic Hepatitis B Virus (HBV) Infection

A Phase 1/2 Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Subjects with Chronic HBV Infection and a Long-term Study to Evaluate the Safety, Tolerability, and Efficacy of BW-20507 in Subjects with Chronic HBV Infection

Sponsor

Argo Biopharma Australia Pty Ltd

Enrollment

32 participants

Start Date

Jan 9, 2024

Study Type

Interventional

Conditions

Chronic Hepatitis B Virus (HBV) Infection

Summary

Part B of the study is investigating the safety and efficacy of multiple ascending doses of BW-20507 in subjects with chronic HBV infection while Part C is a long-term Study to Evaluate the Safety, Tolerability, and Efficacy of BW-20507 in Subjects with Chronic HBV Infection Who is it for? You may be eligible for PART B of the study if you are an adult with chronic Hepatitis B virus infection in the age group between 18-65 years. Subjects who participated in the Part B and completed the Week 32 visit will be automatically enrolled into Part C if his or her HBsAg is = 0.05 IU/ml at Week 32 or following visits in Part B Study details Participants will receive multiple dose of BW-20507 which will be administered as SC injection(s). The estimated total time on Part B, inclusive of screening. treatment and post-treatment follow-up. for each subject. is up to 24 weeks. For subjects consenting to extended follow-up, the estimated total time is up to 52 weeks. Estimated total time for Part C is about 124 weeks. It is hoped that this research will help determine the safe and well tolerated dose and define the dosing regimen of BW-20507 can be safely given to patients with Chronic HBV Infection.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria19

Subjects must meet all the following criteria to be eligible to participate in the study.
Must have given written informed consent and be able to comply with all study requirements.
Males or females aged 18 to 65 aged years, inclusive, at the time of informed consent.
BMI (more than and equal to) 18 and (less than equal to) 32 kg/m2 with body weight >50 kg at screening.
Chronic HBV infection as defined by a positive serum HBsAg for (more than equal to) 6 months at screening.
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)
NUC naive at screening (Only for NUC naive subjects).
HBSAg >50 IU/mL at screening.
HBV DNA <9o IU/mL at screening (Not applicable for NUC naive subjects).
Triplicate 12-lead electrocardiogram(ECG) with normal limits or without clinically significant abnormalities· at screening, as determined by the Investigator.
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..
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.
Completion of the Week 32 visit in Part B with adequate compliance or completion of the Week 48 visit in Part B with adequate compliance within 6 months before screening.
Must have given written informed consent and be able to comply with all study requirements.
HBsAg is = 0.05 IU/ml at Week 32 or following visits in Part B or at screening (for subjects who completed Week 48 visit).
On NUCs therapy for at least 6 months without an interruption of 7 or more consecutive days at screening.
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 90 days following last administration of the study drug and use contraceptives as per study protocol.
Male subjects with female partners of child-bearing potential must agree to use acceptable methods of contraception from study drug administration until 90 days following last administration of the study drug and use contraceptives as per study protocol.

Exclusion Criteria37

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.
Any clinically significant acute condition such as fever (>38 degree celsius) or acute respiratory illness within 7 days of study drug administration.
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.
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).
Active infection with HCV, hepatitis Delta virus (HDV), or HIV at screening.
Use of an investigational agent or device within 30 days or 5 half-lives (whichever is longer) before the first dose of study drug.
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.
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.
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.
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.
Calculated creatinine clearance (less than equal to) 60 ml/min (Cockcroft-Gault equation).
History of chronic liver disease from any cause other than chronic HBV infection.
Diagnosed or suspected hepatocellular carcinoma.
History of hepatic decompensation, including ascites, hepatic encephalopathy and/or esophageal or gastric varices
Currently taking, or has taken within 12 months of screening, any interferon-containing therapy.
History of allergic reaction to a siRNA or GalNAc.
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.
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.
Unresolved drug related SAE from Part B per Investigators’ judgement.
Significant liver fibrosis or cirrhosis defined as FibroScan > 8.5kPa at screening.
Subject has the following laboratory parameters at screening (by local laboratory):
o INR > 1.2 × ULN
o serum ALT or AST > 2 × ULN
Study laboratory tests may be repeated once (eg, for values thought to be erroneous).
Active infection with HCV, hepatitis Delta virus (HDV), or HIV at screening.
Use of an investigational agent (except BW-20507) or device within 6 months before screening.
History or clinical evidence of alcohol or drug abuse, within 6 months before screening.
Calculated creatinine clearance =60 mL/min (Cockcroft-Gault equation) at screening.
Diagnosed or suspected hepatocellular carcinoma.
History of hepatic decompensation, including ascites, hepatic encephalopathy and/or esophageal or gastric varices.
Currently taking, or has taken within 12 months before screening, any interferon-containing therapy.
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.
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.

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Interventions

BW-20507 injection is a sterile solution manufactured through dissolution of BW-20507 API in water with necessary pH adjustment by NaOH or H3P. It will be supplied as a sterile 200 mg/1mL solution fo

BW-20507 injection is a sterile solution manufactured through dissolution of BW-20507 API in water with necessary pH adjustment by NaOH or H3P. It will be supplied as a sterile 200 mg/1mL solution for SC injection. BW-20507 (35, 100, 200, and 400 mg) or a matching placebo (sodium chloride injection, 0.9% w/v) will be administered as SC injection(s). Investigational Product: BW-20507 Dosage Formulation: Solution Route to Administration: Sub-cutaneous Injection which will be administered by study staff The study will be conducted in 2 Parts: • Part A: Subjects will receive a single dose of either BW-20507 or placebo based on their assigned dose in the cohort • Part B: Multiple ascending dose (MAD) phase in subjects with chronic HBV infection where a group of subjects will receive multiple low doses of the drug and the dose is subsequently escalated for further groups, up to a predetermined level. • Part C: Long-term treatment phase in subjects who participated in the Part B and completed the Week 32 visit with HBsAg = 0.05 IU/ml at Week 32 or following visits in Part B. Subjects who completed Part B (Week 48 visit) within 6 months before screening may also participate in Part C if they are deemed eligible. This registration is for PART B and C of the study. PART A Single Ascending dose (SAD-registered in a separate form) - Cohorts 1b, 2b, and 4b will receive BW-20507 at three dose-levels of 100 mg, 200 mg, and 400 mg in subjects with chronic HBV infection on NUC therapy respectively. Cohort 3b will receive three doses of 200 mg of BW-20507 in subjects with chronic HBV infection not on NUC therapy (NUC naïve). Cohort 3b will start NUC therapy based on the Principal Investigator discretion on Day 1. - Method of allocation: Cohorts 1b to 4b will each enroll a minimum of 6 and a maximum of 8 subjects with chronic HBV infection in an open-label fashion to receive three doses of BW-20507 (Day 1, Day 29, Day 57). The doses for MAD protocol will be determined based on safety and pharmacokinetic data from Part A, etc. Part C: For Part C, BW-20507 (300 mg) will be administrated subcutaneously every 4 weeks for 24 weeks (7 doses) and then every 8 weeks for 72weeks (9 doses). Up to 31 subjects from Part B will be enrolled into this part.