This double-blind, randomized, placebo-controlled study will assess the safety and pharmacokinetics of ZB002 in healthy participants and in participants with rheumatoid arthritis (RA). The study consists of 2 parts. Part A: Single Ascending Dose (SAD), which will include only healthy volunteers. Part B: Multiple Ascending Dose (MAD), will commence after completion of the SAD study and will include RA participants.
Part A (SAD): Up to approximately 48 healthy volunteers across 6 cohorts randomized to receive ZB002 or placebo as a single dose. Part B (MAD): Up to approximately 24 participants with RA across 3 cohorts randomized to receive ZB002 or placebo as multiple doses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
72
ZB002 will be administered subcutaneously as per schedule specified in the respective arm.
Placebo will be administered subcutaneously as per schedule specified in the respective arm.
ZB002 will be administered subcutaneously as per schedule specified in the respective arm.
Veritus Research
Melbourne, Australia
NZCR New Zealand Clinical Research
Christchurch, New Zealand
Part A: Safety and Tolerability in HVs
To evaluate the safety and tolerability of ZB002 in HVs by assessing the number, severity and type of adverse events, including changes in laboratory safety test and electrocardiogram (ECG)
Time frame: Day 1 through Day 120
Part B: Safety and Tolerability of multiple doses of ZB002 in participants with RA
To evaluate the safety and tolerability of ZB002 in participants with RA by assessing the number of participants with Treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAE leading to discontinuation
Time frame: Day 1 through Day 176
Part A: Maximum observed serum concentration (Cmax)
Pharmacokinetics
Time frame: Day 1 through Day 120
Part A: Time for Cmax (Tmax)
Pharmacokinetics
Time frame: Day 1 through Day 120
Part A: Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf)
Pharmacokinetics
Time frame: Day 1 through Day 120
Part A: AUC from time 0 to the last quantifiable concentration (AUClast)
Pharmacokinetics
Time frame: Day 1 through Day 120
Part A: Terminal half-life (t1/2)
Pharmacokinetics
Time frame: Day 1 through Day 120
Part A: Apparent clearance following extravascular dosing (CL/F)
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Placebo will be administered subcutaneously as per schedule specified in the respective arm.
Pharmacokinetics
Time frame: Day 1 through Day 120
Part A: Apparent volume of distribution following extravascular administration (Vz/F)
Pharmacokinetics
Time frame: Day 1 through Day 120
Part B (All Doses): Serum trough concentration (Ctrough)
Before repeat-dose administration (or at the end of the dosing interval \[tau\] after the final dose)
Time frame: Day 1 through Day 176
Part B (Doses 1 and 3): Maximum observed serum concentration (Cmax)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Doses 1 and 3): Time for Cmax (Tmax)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Doses 1 and 3): AUC over the dosing interval, tau (AUCtau)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Doses 1 and 3): Accumulation ratio of Cmax (ARCmax)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Doses 1 and 3): Accumulation ratio of AUC (ARAUC)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Dose 3 only): Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Dose 3 only): Terminal half-life (t1/2)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Dose 3 only): AUC from time 0 to the last quantifiable concentration (AUClast)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Dose 3 only): Apparent clearance following extravascular dosing (CL/F)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B (Dose 3 only): Apparent volume of distribution following extravascular (Vz/F)
Pharmacokinetics
Time frame: Day 1 through Day 176
Part B: Serum anti-ZB002 antibody prevalence and incidence
Time frame: Day 1 through Day 176
Part B: Cytokine/chemokine secretion in ex vivo stimulated whole blood
Pharmacodynamic
Time frame: Day 1 through Day 176