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 (ENDURE)

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

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

Study Overview

• Status: Terminated
• Conditions: Coronavirus Disease 2019 (COVID-19)
• Intervention / Treatment: Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]); Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])

Detailed Description

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
• Enrollment (Actual): 251
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35215
      • Research Site
  • California
    • Modesto, California, United States, 95350
      • Research Site
    • Westminster, California, United States, 92683
      • Research Site
  • Florida
    • Hollywood, Florida, United States, 33024
      • Research Site
    • Lake City, Florida, United States, 32055
      • Research Site
    • Miami, Florida, United States, 33125
      • Research Site
    • Miami Lakes, Florida, United States, 33014
      • Research Site
    • Ormond Beach, Florida, United States, 32174
      • Research Site
    • Wesley Chapel, Florida, United States, 33545
      • Research Site
    • West Palm Beach, Florida, United States, 33409
      • Research Site
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Research Site
  • Texas
    • Austin, Texas, United States, 78745
      • Research Site
    • El Paso, Texas, United States, 79925
      • Research Site
  • Virginia
    • Annandale, Virginia, United States, 22003
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 95 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

1. Active treatment for solid tumor and hematologic malignancies.
2. Receipt of solid-organ transplant and taking immunosuppressive therapy.
3. Receipt of chimeric antigen receptor T-cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy).
4. Moderate or severe primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome).
5. 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).

6. 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:

   1. 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.
   2. 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.
   3. Current need for hospitalization or immediate medical attention in a clinic or emergency room service in the clinical opinion of the Investigator.
   4. Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb.
   5. Known history of allergy to any component of the IMP formulation.
   6. 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.
   7. 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
   8. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AEs, SAEs, and AESIs	To evaluate the safety and tolerability of AZD7442	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	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum AZD7442 Concentrations	To evaluate the PK of AZD7442 in serum	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	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	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	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	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.

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• redacted SAP
• redacted CSP
• redacted CRS Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Actual): October 4, 2023
• Study Completion (Actual): October 4, 2023

Study Registration Dates

• First Submitted: May 16, 2022
• First Submitted That Met QC Criteria: May 16, 2022
• First Posted (Actual): May 17, 2022

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: ENDURE
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Anti-Infective Agents; Antiviral Agents; Cilgavimab and tixagevimab drug combination
• Other Study ID Numbers: D8850C00010; 2022-001014-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No