Clinical trial NCT05166421: Study to Evaluate Pharmacokinetic Comparability Between AZD7442 Co-formulation (AZD8895 + AZD1061) vs AZD8895 and AZD1061 Individually in Adult Healthy Participants
Official title: Phase 1, Randomized, Open Label, Three-arm, Single Dose, Parallel Group Study to Compare AZD7442 (AZD8895 + AZD1061) Pharmacokinetic Exposure Following Intramuscular Administration as a Co-formulation Versus Administration From Two Separate Vials of the Individual Monoclonal Antibodies in Adult Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Corona Virus Disease
Keywords: Monoclonal antibodies
Adult healthy participants
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-12-22
Enrollment: 224
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will assess pharmacokinetic (PK) comparability between different formulations of AZD7442, which is a combination of two individual monoclonal antibodies (mAbs), AZD8895 and AZD1061.

Detailed description: This is a randomized, open label, three-arm, single dose, parallel group, multi-center, PK comparability study.

Eligible healthy participants will be randomized in a 1:1:1 ratio between the 3 treatment groups. Each participant will receive AZD7442 as either a single intramuscular (IM) dose (co-formulation; AZD8895 + AZD1061), or as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) from either clonal cell line material or cell pool material.

Following an observation and PK and pharmacodynamic (PD) sample collection, post-dose, participants will be discharged from the Clinical Unit. During the Follow-up Period of approximately 1 year, participants will return as outpatient follow-up visits until Day 361.

The total duration of the study for a participant will be approximately 389 days comprising of a Screening Period that can last up to 28 days, Treatment Period of 1 day, and a Follow up Period of 360 days.

Eligibility criteria: Inclusion Criteria:

* Healthy participants according to medical history, physical examination, and baseline safety laboratory tests.
* Documented negative results of a Severe Acute Respiratory Syndrome Corona Virus 2 reverse transcriptase polymerase chain reaction (SARS-CoV-2 RT-PCR) test collected ≤ 3 days prior to investigational medicinal drug (IMP) dose administration (Day 1) or a negative rapid SARS-CoV-2 antigen test on Day 1 (pre-dose).
* Able to complete the Follow-up period up to Day 361 as required by the protocol.
* Body weight ≥ 50 kg to ≤ 110 kg at screening and a Body mass index ≥ 18.0 to ≤ 30 kg/m\^2 at the time of the Screening Visit.

Exclusion Criteria:

* Known history of allergy or reaction to any component of AZD7442 (AZD8895 + AZD1061).
* History of infection with SARS or Middle East Respiratory Syndrome.
* Positive SARSCoV-2 result based on available data at screening or at Day 1.
* Any clinical signs and symptoms consistent with Corona virus disease 2019 (COVID-19), eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
* History of clinically significant bleeding disorder.
* Active infection with hepatitis B or C or positive test for hepatitis C or for hepatitis B surface antigen at screening.
* Immunodeficiency due to illness, including HIV infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone.
* Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study
* Any prior receipt of another mAb indicated for the prevention or treatment of SARS CoV-2 or COVID-19.
* Receipt of a mAb within 6 months or 5 antibody half-lives.
* Receipt of a COVID-19 vaccination ≤ 14 days before IMP administration (Day 1) or plan to receive a COVID-19 vaccination ≤ 14 days after IMP dose (such participants can subsequently be included in the study once they have reached \> 14 days after their last dose of vaccine).

Primary outcomes:
measure: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)
timeFrame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
measure: Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast)
timeFrame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
measure: Maximum Observed Serum (Peak) Concentration (Cmax)
timeFrame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Secondary outcomes:
measure: Time to Maximum Observed Serum Concentration (Tmax)
timeFrame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
measure: Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d)
timeFrame: Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, and 31
measure: Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d)
timeFrame: Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31 and 61
measure: Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d)
timeFrame: Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61 and 91
measure: Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d)
timeFrame: Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61, 91, and 181
measure: Time of Last Quantifiable Concentration (Tlast)
timeFrame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 382
measure: Terminal Half-life (t½λz)
timeFrame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
measure: Apparent Clearance After Extravascular Administration (CL/F)
timeFrame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
measure: Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)
timeFrame: Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From Day 1 until Follow-up visit (Day 361)
measure: Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies
timeFrame: Day 1 (Pre-dose) until Follow-up visit (Day 361)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Research Site
state: Alabama
city: Cullman
country: United States
facility: Research Site
state: Alabama
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Chula Vista
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Long Beach
country: United States
facility: Research Site
state: California
city: North Hollywood
country: United States
facility: Research Site
state: California
city: Edgewater
country: United States
facility: Research Site
state: Florida
city: Lake Worth
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Meridian
country: United States
facility: Research Site
state: Idaho
city: Berlin
country: United States
facility: Research Site
state: New Jersey
city: Union
country: United States
facility: Research Site
state: South Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
Study officials:
References: