A Phase II Randomized, Open-label, Multicenter, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, a Combination Product of Two Monoclonal Antibodies (Tixagevimab and Cilgavimab), for Pre-exposure Prophylaxis of COVID-19
AZD7442, a combination of 2 monoclonal antibodies (tixagevimab \[investigational name, AZD8895\] and cilgavimab \[investigational name, AZD1061\]), is being developed for the prophylaxis and treatment of coronavirus disease 2019 (COVID-19). This Phase II dose-ranging study will investigate the safety, immunogenicity, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of AZD7442 repeat dosing regimens for preexposure prophylaxis of COVID-19 in adults and pediatric individuals (≥ 12 years of age weighing at least 40 kg), who are moderately to severely immunocompromised.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
251
Arm A - Day 1: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region. Arm A - Days 92, 183, 274, 365: 300 mg AZD7442 administered sequentially as a 1.5 mL IM injection containing 150 mg tixagevimab (AZD8895) and a 1.5 mL IM injection containing 150 mg cilgavimab (AZD1061), one injection in each gluteal region.
Arm B - Day 1: 1200 mg AZD7442 (600 mg tixagevimab \[AZD8895\] and 600 mg cilgavimab \[AZD1061\]) administered by IV infusion. Arm B - Days 183, 365: 600 mg AZD7442 administered sequentially as a 3 mL IM injection containing 300 mg tixagevimab (AZD8895) and a 3 mL IM injection containing 300 mg cilgavimab (AZD1061), one injection in each gluteal region.
Research Site
Birmingham, Alabama, United States
Research Site
Modesto, California, United States
Research Site
Westminster, California, United States
Research Site
Hollywood, Florida, United States
Research Site
Lake City, Florida, United States
Research Site
Miami, Florida, United States
Research Site
Miami Lakes, Florida, United States
Research Site
Ormond Beach, Florida, United States
Research Site
Wesley Chapel, Florida, United States
Research Site
West Palm Beach, Florida, United States
...and 6 more locations
AEs, SAEs, and AESIs
To evaluate the safety and tolerability of AZD7442
Time frame: Safety data were recorded from the time of the first IMP administration throughout the study for an average safety follow up time of 48.85 weeks. This was shorter than the planned one of 105 weeks due to FDA's request to halt dosing.
ADA in Serum Responses
To evaluate the immunogenicity of AZD7442
Time frame: Serum ADA were assessed through the treatment period at the specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365, 456 days or early discontinuation visit after the first IMP administration.
Serum AZD7442 Concentrations
To evaluate the PK of AZD7442 in serum
Time frame: Serum PK was assessed through the treatment period at the specific timepoints: day 1 post-dose (600mg Q6M arm only), 3, 11, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early discontinuation visit after the first IMP administration.
Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay)
To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time frame: SARSCoV-2 nAbs (Wild Type Assay) were assessed through the treatment period at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.
Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay)
To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time frame: SARSCoV-2 nAbs (Pseudo Neutralization Assay) were assessed through the study at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.
Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay)
To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time frame: SARSCoV-2 nAbs (Wild Type Assay) were assessed through the treatment period at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.
Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay)
To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time frame: SARSCoV-2 nAbs (Pseudo Neutralization Assay) were assessed through the study at these specific timepoints: baseline, 29, 92, 121 (300mg Q3M arm only), 183, 212, 274, 365 days or early termination visit after the first IMP administration.
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