None listed
Conditions
Brief summary
This study is investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single ascending dose of BW-20829 in subjects with elevated lipoprotein(a) in 5 dose level cohorts (up to 3 optional cohorts with 24 subjects may be added). Approximately 40 men and women aged (more than equal to) 18 to (less than equal to) 65 years who fulfill the inclusion and exclusion criteria will be enrolled at sites in Australia. Eligible subjects will be admitted to the clinical research unit on Day -1, dosed on Day 1, discharged on Day 2 (24 hours post-dose), and return for outpatient visits through Day365. Within each cohort, 8 subjects will be randomized in a 3:1 ratio to receive a single dose of BW-20829 (n=6) or placebo (n=2) on Day 1 in a double-blind fashion.
Interventions
Treatment: Drugs - BW-20829 or placebo(sodium chloride injection, 0.9% w/v)
5 cohort doses (with up to 3 optional cohorts may be added):
8 subjects will be randomized in a 3:1 ratio to receive a single dose of BW-20829 (n=6) or placebo (n=2) on Day 1 in a double-blind fashion. Cohorts 1 to 5 will receive BW-20829 doses of 15, 50, 150, 300, and 600mg, or placebo respectively.
Maximum of additional 4 participants in a 3:1 ratio for PD assessment will be enrolled if deemed necessary.
Dose escalat
Treatment: Drugs - BW-20829 or placebo(sodium chloride injection, 0.9% w/v) 5 cohort doses (with up to 3 optional cohorts may be added): 8 subjects will be randomized in a 3:1 ratio to receive a single dose of BW-20829 (n=6) or placebo (n=2) on Day 1 in a double-blind fashion. Cohorts 1 to 5 will receive BW-20829 doses of 15, 50, 150, 300, and 600mg, or placebo respectively. Maximum of additional 4 participants in a 3:1 ratio for PD assessment will be enrolled if deemed necessary. Dose escalation will be based on the SRC’s assessment. For each cohort, all data (safety, tolerability, and trailing plasma PK and PD data) for a minimum of 6 evaluable subjects through to Day 8, as well as cumulative data from evaluable subjects across previous cohorts, will be reviewed by the SRC prior to dose escalation. Participant will be admitted to the Phase 1 Clinical Trial Facility on Day -1 to take a 24-hour confinement and single dose of study drug will be administered by site staff on Day 1 to ensure adherence to the intervention. Individual patient records of subjects will be reviewed by monitor for intervention adherence. The duration of administration: single dose BW-20829 or placebo will be subcutaneously administered by registered nurse at Phase 1 clinical trial site. The used and/or partially used vials can be disposed of per local practice. If the used and/or partially used vials cannot be disposed of at site, they will be returned, along with the unused vials, to the sponsor or its agent after receipt of written authorization from Sponsor. For 3 optional cohorts: • one optional cohort may be up to the 900 mg dose, especially if needed for TQT study, • one optional cohort is at a dose below 15 mg, as this low dose will strengthen model prediction for Ph2&3. • one optional cohort is to make one dose larger, and may not be needed. Will be informed by emerging data. It will depend on the variability of response of individual participants and if additional data will improve modeling prediction for Ph2&3. The dose escalation for optional cohort like 900mg will be based on the SRC’s assessment and still need the sentinel safety assessment. Other optional cohort(s) to assess doses the same or lower than those already administered to participants and approved by the SRC will not require SRC review. Optional cohorts at same or lower doses than already administered will not require sentinel dosing, be randomized 3:1.
Sponsors
Argo Biopharma Australia Pty Ltd
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Must have given written informed consent and be able to comply with all study requirements. 2. Males or females aged 18 to 65 years old, inclusive, at the time of informed consent. 3. Lp(a) >=50 mg/dL (125 nmol/L). 4. Body mass index >=18 and <=35 kg/m2 with body weight >50 kg. 5. 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, can participate if they are using highly effective methods of contraception from 28 days prior to dosing until 12 weeks following administration of the study drug. 6. Male subjects with female partners of child-bearing potential must agree to use acceptable methods of contraception from 28 days prior to dosing until 12 weeks following administration of the study drug.
Exclusion criteria
1. Any uncontrolled or serious disease, or any medical or surgical condition including evidence of unstable cardiovascular disease, and other serious medical or psychiatric illness/condition. 2. Any history of clinically overt cardiovascular disease, defined as acute coronary syndromes, myocardial infarction, stable angina, coronary or other revascularization, ischemic stroke or transient ischemic attack and atherosclerotic peripheral arterial disease. 3. Any clinically significant acute condition such as fever (>38°c) or acute respiratory illness within 7 days of study drug administration. 4. Clinical laboratory findings outside of range are deemed clinically significant by the investigator at screening or Day -1. 5. 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 investigator).
Outcome results
None listed