A Randomized, Open-label, Dose-ranging Study in Adults and Pediatric Individuals ≥ 12 Years of Age to Assess the Safety, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of AZD7442, for Pre-exposure Prophylaxis of COVID-19

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Coronavirus Disease 2019 (COVID-19)

Intervention / Treatment
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* Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])
* Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. For pediatric participants: informed assent is to be provided by the participant; informed consent must be provided by the participant's legal guardian 2. Ensure that participants who are considered by the Investigator clinically unable to consent at screening and who are entered into the study by the consent of a legally acceptable representative show evidence of assent, as applicable in accordance with local regulations. 3. Participant must be an adult (≥ 18 years of age) or pediatric individual (≥ 12 to < 18 years of age weighing ≥ 40 kg) at the time of signing the ICF or assent (for pediatric participants). 4. Individuals with medical conditions or treatments that may result in moderate to severe immune compromise or an inadequate immune response to COVID-19 vaccination include but are not limited to: Active treatment for solid tumor and hematologic malignancies. Receipt of solid-organ transplant and taking immunosuppressive therapy. Receipt of chimeric antigen receptor T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy). Moderate or severe primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome). Advanced or untreated HIV infection (people with HIV and history of CD4 cellcounts < 200/mm3, history of an AIDS-defining illness without immune reconstitution, or clinical manifestations of symptomatic HIV). Active treatment with systemic high-dose corticosteroids (ie, ≥ 20 mg prednisone or equivalent per day when administered for ≥ 2 weeks), alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents classified as severely immunosuppressive, tumor necrosis factor blockers, and other biologic agents that are immunosuppressive or immunomodulatory (eg, B-cell depleting agents). 5 Documented negative SARS-CoV-2 RT-PCR test from an NP specimen collected ≤ 3 days prior to Day 1 or a negative SARS-CoV-2 rapid antigen test from an NP specimen at screening. Exclusion Criteria: Any clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnea, sore throat, fatigue for ≥ 5 days or confirmed COVID-19 infection by appropriate laboratory test within 28 days prior to screening. Prior COVID-19 infection is not an exclusion. History or current hospitalization for worsening disease during the one month prior to screening, with no change in condition at the time of study enrollment as judged by the Investigator. Current need for hospitalization or immediate medical attention in a clinic or emergency room service in the clinical opinion of the Investigator. Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb. Known history of allergy to any component of the IMP formulation. History of clinically significant bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IV infusions or venepuncture. Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data Any co-morbidity requiring surgery within 7 days prior to study entry, or that is considered life-threatening in the opinion of the Investigator within 30 days prior to study entry. 9 Any prior receipt of investigational or licensed mAb or other biologic indicated for the prevention or treatment of SARS-CoV-2 or COVID-19 within 5 half-lives prior to screening or expected administration immediately after enrollment. 10 Have received a COVID-19 vaccination ≤ 14 days before Day 1 or plan to receive a COVID-19 vaccination ≤ 14 days after Day 1 (Such participants can subsequently be included in the study once they have reached > 14 days after their last dose of vaccine). 11 Receipt of convalescent COVID-19 plasma treatment within 90 days prior to screening. 12 Receipt of any IMP in the preceding 90 days or 5 half-lives, whichever is longer, or expected receipt of IMP during the period of study follow-up, or concurrent participation in another interventional study. 13 Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. 14 For women only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding. 15 Previous randomization in the present study. 16 Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to randomization. 17 Employees of the Sponsor involved in planning executing, supervising, or reviewing the AZD7442 program, clinical study site staff, or any other individuals involved with the conduct of the study, or immediate family members of such individuals. 18 In nations, states, or other jurisdictions that for legal or ethical reasons bar the enrollment of participants who lack capacity to provide their own informed consent, such subjects are excluded.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm A<br>600 mg AZD7442 following 300 mg AZD7442 every 3 months (5 doses totally) | Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])<br>* 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.<br>|
| Other: Arm B<br>1200mg AZD7442 following 600 mg AZD7442 every 6 months (3 doses totally) | Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | To evaluate the safety and tolerability of AZD7442 | 2 years | 
| Serious Adverse Events | To evaluate the safety and tolerability of AZD7442 | 2 years | 
| Adverse Events of Special Interest | To evaluate the safety and tolerability of AZD7442 | 2 years | 
| Incidence of ADA in serum | To evaluate the immunogenicity of AZD7442 | 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum AZD7442 concentrations | To evaluate the PK of AZD7442 in serum | 15 months | 
| Changes from baseline in GMTs and GMFRs values in SARS-CoV-2 nAbs | To determine anti-SARS-CoV-2 nAb levels in serum after administration of AZD7442 | 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ENDURE