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A First in Human Study to Assess Safety, Tolerability, Pharmacokinetics of ABI-4334 in Healthy Subjects

Phase 1
Completed
Conditions
Chronic Hepatitis B
Interventions
Drug: ABI-4334 Tablet
Drug: ABI-4334 Placebo
Registration Number
NCT05569941
Lead Sponsor
Assembly Biosciences
Brief Summary

This study is designed to assess safety, tolerability, and PK of single ascending doses (SAD) of ABI-4334 in Part A and multiple-ascending doses (MAD) of ABI-4334 in Part B in healthy subjects. Effect of food will also be evaluated in Part A.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
54
Inclusion Criteria
  • Body mass index (BMI) between 18.0 and 30.0 kg/m2
  • In good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
  • Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1
  • Agreement to comply with protocol-specified contraceptive requirements
Exclusion Criteria
  • Positive results for any of the following serology tests, HBsAg, hepatitis B core antibody (HBcAb IgM), hepatitis C virus antibody (HCV Ab), or HIV-1 or -2 antibody
  • History of any illness that, in the opinion of the Investigator, might confound the results of the study, pose an additional risk in administering study drug to the subject, or a condition known to interfere with the absorption/ distribution/elimination of drugs.
  • History of any significant drug-related allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, urticaria, or multiple drug allergies
  • History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
  • Has participated in a clinical study involving administration of either an investigational or a marketed drug within 2 months before Screening

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part A: SAD Cohorts 1-5 ABI-4334 TabletABI-4334 TabletA single dose of ABI-4334 will be administered on Day 1 in dose-escalation cohorts with a starting dose of 30 mg. The doses for subsequent cohorts will be determined by evaluation of safety and PK data from previous cohorts.
Part A: SAD Cohorts 1-5 ABI-4334 Placebo TabletABI-4334 PlaceboA single dose of placebo matching ABI-4334 will be administered on Day 1.
Part A: SAD Fed Cohorts 6-7 ABI-4334 TabletABI-4334 TabletA single dose of ABI-4334 will be administered after a high-fat meal on Day 1 in cohort 6. A single dose of ABI-4334 will be administered on two separate occasions, once fasted and once after a high-fat meal in cohort 7. The dose administered will be determined after evaluation of cumulative safety and PK data from cohorts 1-5.
Part A: SAD Fed Cohorts 6 ABI-4334 Placebo TabletABI-4334 PlaceboA single dose of placebo matching ABI-4334 will be administered on Day 1 after a high-fat meal on Day 1 in cohort 6.
Part B: MAD Cohorts 1-2 ABI-4334 TabletABI-4334 TabletOnce-daily doses of ABI-4334 will be administered from Day 1 to Day 8. Cohort B1 will receive a dose determined from evaluation of the data from the SAD cohorts. The doses for the subsequent cohort will be determined by evaluation of safety and PK data from previous cohorts.
Part B: MAD Cohorts 1-2 ABI-4334 Placebo TabletABI-4334 PlaceboOnce-daily doses of placebo matching ABI-4334 will be administered from Day 1 to Day 8.
Primary Outcome Measures
NameTimeMethod
Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory resultsUp to Day 14
Secondary Outcome Measures
NameTimeMethod
SAD Cohorts 1-7: Area Under the Plasma Concentration Time Curve (AUC) of ABI-4334before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Comparison of AUC between fasted and fed treatments of ABI-4334before and at pre-specified time points up to 144 hours after dosing
MAD Cohorts 1-2: Cmax of ABI-4334before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: Tmax of ABI-4334before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: t 1/2 of ABI-4334before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: CL/F of ABI-4334before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
MAD Cohorts 1-2: Vz/F of ABI-4334before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
SAD Cohorts 1-7: Apparent Terminal Elimination Half Life (t 1/2) of ABI-4334before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Maximum Observed Plasma Concentration (Cmax) of ABI-4334before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Time to Cmax (Tmax) of ABI-4334before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Apparent Systemic Clearance (CL/F) of ABI-4334before and at pre-specified time points up to 144 hours after dosing
MAD Cohorts 1-2: AUC of ABI-4334before and at pre-specified time points up to 24 hours after dosing on Day 1; before dosing on days 2-7; before and up to 120 hours after dosing on Day 8
SAD Cohorts 1-7: Apparent Volume of Distribution (Vz/F) of ABI-4334before and at pre-specified time points up to 144 hours after dosing
SAD Cohorts 1-7: Comparison of Cmax between fasted and fed treatments of ABI-4334before and at pre-specified time points up to 144 hours after dosing

Trial Locations

Locations (1)

New Zealand Clinical Research

🇳🇿

Grafton, Auckland, New Zealand

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