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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05375760
Recruitment Status : Terminated (Sponsor terminated after review of FDA's request to halt further dosing (30Mar2023) given that AZD7442 is not active against >99% of the currently circulating SARS-CoV-2 variants in the USA, the benefit risk assessment may not be favorable)
First Posted : May 17, 2022
Last Update Posted : November 7, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Coronavirus Disease 2019 (COVID-19) Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 251 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : June 9, 2022
Actual Primary Completion Date : October 4, 2023
Actual Study Completion Date : October 4, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.


Arm B
1200mg AZD7442 following 600 mg AZD7442 every 6 months (3 doses totally)
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.





Primary Outcome Measures :
  1. Adverse Events [ Time Frame: 2 years ]
    To evaluate the safety and tolerability of AZD7442

  2. Serious Adverse Events [ Time Frame: 2 years ]
    To evaluate the safety and tolerability of AZD7442

  3. Adverse Events of Special Interest [ Time Frame: 2 years ]
    To evaluate the safety and tolerability of AZD7442

  4. Incidence of ADA in serum [ Time Frame: 15 months ]
    To evaluate the immunogenicity of AZD7442


Secondary Outcome Measures :
  1. Serum AZD7442 concentrations [ Time Frame: 15 months ]
    To evaluate the PK of AZD7442 in serum

  2. Changes from baseline in GMTs and GMFRs values in SARS-CoV-2 nAbs [ Time Frame: 15 months ]
    To determine anti-SARS-CoV-2 nAb levels in serum after administration of AZD7442



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05375760


Locations
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United States, Alabama
Research Site
Birmingham, Alabama, United States, 35215
United States, California
Research Site
Modesto, California, United States, 95350
Research Site
Westminster, California, United States, 92683
United States, Florida
Research Site
Hollywood, Florida, United States, 33024
Research Site
Lake City, Florida, United States, 32055
Research Site
Miami Lakes, Florida, United States, 33014
Research Site
Miami, Florida, United States, 33125
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
United States, Illinois
Research Site
Chicago, Illinois, United States, 60640
United States, Missouri
Research Site
Saint Louis, Missouri, United States, 63141
United States, Tennessee
Research Site
Knoxville, Tennessee, United States, 37920
United States, Texas
Research Site
Austin, Texas, United States, 78745
Research Site
El Paso, Texas, United States, 79925
United States, Virginia
Research Site
Annandale, Virginia, United States, 22003
Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05375760    
Other Study ID Numbers: D8850C00010
2022-001014-20 ( EudraCT Number )
First Posted: May 17, 2022    Key Record Dates
Last Update Posted: November 7, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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.
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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
ENDURE
Additional relevant MeSH terms:
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COVID-19
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Cilgavimab and tixagevimab drug combination
Antiviral Agents
Anti-Infective Agents