In this first-in-humans dose escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated for safety, tolerability, pharmacokinetics, and generation of anti-drug antibodies (ADAs). The study is intended to enable future studies of AZD7442's efficacy in preventing and treating COVID-19.
This is a Phase I, first time in human, randomised, double-blind, placebo-controlled, and dose escalation study. The study will comprise of: 1. A Screening Period of up to 27 days (Day -28 through Day -2); 2. A Treatment Period during which participants will be resident at the Clinical Unit from Day -1, 1 day before Investigational Medicinal Product (IMP) administration (on Day 1) until at least 24 hours after IMP administration, will be discharged on Day 2 after all safety evaluations have been completed, and 3. A Follow up Period lasting 360 days (through to Day 361) after the IMP dose. The study will be conducted at a single study centre in United Kingdom.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
Participants randomized to AZD7442 will be administered dose 1, each in Cohort 1a (IM) and Cohort 1b (IV). Participants in Cohort 2 and 3 will receive AZD7442 (IV) doses 2 and 3, respectively. Participants in Cohort 4 will receive AZD7442 (IV) dose 4.
Participants randomised to placebo will receive the same volume of solution as participants on active treatment.
Research Site
Harrow, United Kingdom
Number of Participants With Adverse Events (AEs) and Serious AEs
The safety and tolerability of AZD7442 administered IV or IM to healthy adult participants 18 to 55 years of age was evaluated.
Time frame: From screening day (Day -28) until Follow-up/end of treatment visit (Day 361)
Maximum Serum Concentration (Cmax) of AZD7442
The single dose Cmax of AZD7442 and of the individual monoclonal antibodies (mAbs) in serum were evaluated.
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
Time to Reach Maximum Serum Concentration (Tmax) of AZD7442
The single dose tmax of AZD7442 and of the individual mAbs in serum was evaluated
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
Terminal Elimination Half-life (t½λz) of AZD7442
The single dose t½λz of AZD7442 and of the individual mAbs in serum was evaluated.
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
Area Under the Concentration Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of AZD7442
The single dose AUClast of AZD7442 and of the individual mAbs in serum was evaluated.
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
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Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of AZD7442
The single dose AUCinf of AZD7442 and of the individual mAbs in serum was evaluated. The bioavailability (F) of AZD7442 Dose 1 administered by IM was calculated as the ratio of geometric mean AUCinf after IM to IV, for mAb AZD8895 and mAb AZD1061 is also presented.
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
Systemic Clearance (CL) of AZD7442 IV Infusion
The single dose CL of AZD7442 and of the individual mAbs in serum was evaluated.
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
Apparent Total Clearance (CL/F) of AZD7442 IM Injection
The single dose CL/F of AZD7442 and of the individual mAbs in serum was evaluated.
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD7442
The single dose Vz/F of AZD7442 and of the individual mAbs in serum was evaluated.
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
Volume of Distribution at Steady State (Vss) of AZD7442 IV Infusion
The single dose Vss of AZD7442 and of the individual mAbs in serum was evaluated.
Time frame: Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)
Percentage of Participants Who Have Positive Antidrug Antibodies (ADA) of AZD8895 and AZD1061
The ADA response to AZD7442 in serum was evaluated.
Time frame: Day 361 (Post dose)