CompletedPhase 2ACTRN12623000709640

A Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BW-20507 in Healthy Subjects

A Phase 1/2 Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BW-20507 in Healthy Subjects 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

Aug 2, 2023

Study Type

Interventional

Conditions

Chronic Hepatitis B Virus (HBV) Infection

Summary

PART A of the study is investigating the safety and efficay of Single ascending dose of BW-20507 in healthy volunteers in 4 dose level cohorts. Who is it for? You may be eligible for PART A this study if you are a healthy adult aged 18 to 60 years old. Study details Participants will receive either each dose of BW-20507 or placebo which will be administered as SC injection(s). The estimated total time on Part A, inclusive of screening and follow-up, for each subject is up to 8 weeks. The duration of screening is 4 weeks. The duration of treatment is a single dose based on the assigned dose level. The duration of follow-up is 4 weeks after study drug administration. It is hoped that this research will help determine the safe and well toerated 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: 60 Yearss

Inclusion Criteria22

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 60 aged years, inclusive, at the time of informed consent.
BMI (more than equal to) 18 and (less than equal to) 32 kg/m2 with body weight >50 and (less than equal to) 120 kg.
Triplicate 12-lead electrocardiogram (ECG) with normal limits or without clinically significant abnormalities* at screening and on Day -1, 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 90 days following administration of the study drug as per study protocol.
Male subjects with female partners of child-bearing potential must agree to use acceptable methods of contraception* from screening until 90 days following administration of the study drug as per protocol.
'clinically significant abnormalities*
Clinically significant ECG findings include, but are not limited to:
o QTcF interval > 450 ms (male) or 470 ms (female)
o QTcF interval < 340 ms
o PR interval < 120 ms
o PR interval > 220 ms, intermittent second or third-degree AV block, or AV
dissociation.
o RBBB, LBBB, IBBB, or IVCD
'effective methods of contraception* 'acceptable methods of contraception*
Hormonal methods of contraception including oral contraceptives containing combined estrogen and progesterone, a vaginal ring, injectable and implantable hormonal contraceptives, intrauterine hormone-releasing system (e.g. Mirena) and progestogen-only hormonal contraception associated with inhibition of ovulation
o Nonhormonal intrauterine device (IUD)
o Bilateral tubal occlusion
o Vasectomised subject/partner with documented azoospermia 90 days after procedure, if that partner is the sole sexual partner.
o True abstinence: when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception
For female subjects and female partners of subjects, hormonal contraceptives should begin at least 28 days prior to screening to ensure contraceptive is in full effect. Subjects will not be allowed to donate ova or sperm during the study.

Exclusion Criteria20

Any clinically significant medical condition or clinically significant abnormality in laboratory parameters that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.
Hospitalization for any reason within 60 days prior to screening.
Any clinically significant acute condition such as fever (>38 degree celsius) or acute respiratory illness within 7 days of study drug administration.
Systolic blood pressure (more than equal to) 140 mmHg and/or diastolic blood pressure (more than equal to) 90 mmHg after at least 5 minutes resting (sitting or supine) at screening.
Any liver function panel analyte value >1.2 ×upper limits of normal (ULN) which includes aspartate transaminase (AST), alanine transaminase (ALT), total bilirubin (TBIL), and alkaline phosphatase (ALP) at screening.
International normalized ratio (INR) above 1.5 at screening.
Calculated creatinine clearance (less than equal to) 60 mL/min (Cockcroft-Gault equation).
Use of an investigational agent or device within 30 days or 5 half-lives (whichever is longer) prior to dosing or current participation in an investigational study.
Used prescription drugs, excluding oral contraceptive pills, within 14 days or 5 halflives (whichever is longer) before the dose of study drug.
Used over-the-counter medications, excluding routine vitamins and paracetamol, within 7 days or 5 half-lives (whichever is longer) before the dose of study drug, unless determined by the Investigator and Sponsor to be not clinically relevant.
Known history or test positive for HBsAg, hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. (Subjects with previous or treated hepatitis B or hepatitis C are not allowed to participate.)
Use of more than 10 tobacco/nicotine-containing products or equivalent per day within 30 days prior to screening.
History or clinical evidence of alcohol abuse, within the 12 months before screening. Alcohol abuse is defined as a regular weekly intake of more than 21 units for males and 14 units for females (unit: 1 glass of wine [125 mL] = 1 measure of spirits [30 mL] = one-half pint of beer [284 mL]).
History or clinical evidence of drug abuse, within the 12 months before screening. Drug abuse is defined as compulsive, repetitive, and/or chronic use of drugs or other substances with or without problems related to their use and/or where stopping or a reduction in dose will lead to withdrawal symptoms (in the judgement of the Investigator).
Positive test for alcohol or drugs of abuse at screening and Day -1.
History of allergic reaction to a synthetic small interfering RNA (siRNA) or Nacetylgalactosamine (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.
Donated or lost >200 mL of blood within 30 days prior to screening.
With abdominal skin conditions such as tattoos, active skin diseases (inflammation, rashes, etc.) which in the opinion of the investigator may impact the subcutaneous administration of study drug and/or visibility of injection site reactions.
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 active pharmaceutical ingredient (API) in water with necessary pH adjustment by NaOH or H3P04. It will be supplie

BW-20507 injection is a sterile solution manufactured through dissolution of BW-20507 active pharmaceutical ingredient (API) in water with necessary pH adjustment by NaOH or H3P04. 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 the study staff The study will be conducted in 2 Parts: • Part A: Single ascending dose (SAD) phase in healthy subjects where subjects will receive a single dose of either BW-20507 or placebo based on their assigned dose in cohort. • Part B: Multiple ascending dose (MAD) phase in subjects with chronic HBV infection PART A Cohorts are- Cohort A1: A single 35mg dose of BW-20507 or placebo Cohort A2: A single 100mg dose of BW-20507 or placebo Cohort A3: A single 200mg dose of BW-20507 or placebo Cohort A3: A single 400mg dose of BW-20507 or placebo This registration is for the PART A of the study. Part B: Multiple ascending dose (MAD - registered in a separate form)