This study will evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single ascending doses of AZD6912 administered subcutaneously (SC) in healthy participants.
In this First-In-Human (FiH) study, eligible participants will be randomly assigned to 6 cohorts in a 3:1 ratio to receive either a single dose of AZD6912 SC or placebo. The first 2 participants in each cohort will be dosed as a sentinel pair, with one receiving AZD6912 SC and the other receiving placebo. The study will comprise of, a screening period of 70 days, a treatment period where participants will stay at the Clinical Unit from the day before study intervention administration until at least 240 hours and will be discharged on Day 11. Outpatient visits would start weekly from Day 15, then bi-weekly from Day 43, 4-weekly from Day 99, and 6-weekly from Day 155, with additional follow-up visits approximately every 4 weeks as needed until complement activity returns to the normal range. The study will last approximately 25 months, including the optional Japanese cohorts, with each participant participating for about 38 weeks or longer until complement activity returns to normal range (per local laboratory).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
40
Research Site
Montreal, Quebec, Canada
Research Site
Harrow, United Kingdom
Number of participants with adverse events (AEs)
To assess the safety and tolerability of AZD6912 in healthy participants.
Time frame: From screening (Day -70) to last follow up visit (Day 197- approximately 38 weeks)
Maximum observed plasma (peak) drug concentration (Cmax) of AZD6912
To characterise the Cmax of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Area under plasma concentration-time curve from zero to infinity (AUCinf) of AZD6912
To characterise AUCinf of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast) of AZD6912
To characterise the AUClast of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD6912
To characterise tmax of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Time of last measurable concentration (tlast) of AZD6912
To characterise tlast of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Terminal elimination half-life (t½λz) of AZD6912
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To characterise t½λz of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Dose normalised AUClast (AUClast/D) of AZD6912
To characterise AUClast/D of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Dose normalised AUCinf (AUCinf/D) of AZD6912
To characterise AUCinf/D of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Dose normalised Cmax (Cmax/D) of AZD6912
To characterise Cmax/D of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD6912
To characterise CL/F of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Volume of distribution (apparent) at steady state following extravascular administration (based on terminal phase) (Vz/F) of AZD6912
To characterise Vz/F of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Percent change from baseline in plasma concentrations of Complement factor B (CFB) protein
To assess the PD effects of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)
Percent change from baseline in serum of Complement functional activity (CAP)
To assess the PD effects of single ascending doses of AZD6912 in healthy participants.
Time frame: From randomization to Day 197 (up to 28 weeks)