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

NCT05375760 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: D8850C000102022-001014-20
• Study Type: interventional
• Target: 251
• Locations: 1 country
• Sites: 16

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

Conditions

Coronavirus Disease 2019 (COVID-19)

Keywords

ENDURE

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Serum AZD7442 Concentrations

  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)

  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)

  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)

  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)

  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.

Study Arms (2)

Arm A

OTHER

600 mg AZD7442 following 300 mg AZD7442 every 3 months (5 doses totally)

Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])

Arm B

OTHER

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

Biological: AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061])

Interventions

AZD7442 (tixagevimab [AZD8895] + cilgavimab [AZD1061]) BIOLOGICAL

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 A

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. 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).
• \. 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).
• 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.

You may not qualify if:

• 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.
• 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.
• 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).
• Receipt of convalescent COVID-19 plasma treatment within 90 days prior to screening.
• 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.
• 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.
• For women only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.
• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (16)

Research Site

Birmingham, Alabama, 35215, United States

Location

Research Site

Modesto, California, 95350, United States

Location

Research Site

Westminster, California, 92683, United States

Location

Research Site

Hollywood, Florida, 33024, United States

Location

Research Site

Lake City, Florida, 32055, United States

Location

Research Site

Miami, Florida, 33125, United States

Location

Research Site

Miami Lakes, Florida, 33014, United States

Location

Research Site

Ormond Beach, Florida, 32174, United States

Location

Research Site

Wesley Chapel, Florida, 33545, United States

Location

Research Site

West Palm Beach, Florida, 33409, United States

Location

Research Site

Chicago, Illinois, 60640, United States

Location

Research Site

St Louis, Missouri, 63141, United States

Location

Research Site

Knoxville, Tennessee, 37920, United States

Location

Research Site

Austin, Texas, 78745, United States

Location

Research Site

El Paso, Texas, 79925, United States

Location

Research Site

Annandale, Virginia, 22003, United States

Location

Related Links

• redacted SAP
• redacted CSP
• redacted CRS Synopsis

MeSH Terms

Conditions

COVID-19

Interventions

cilgavimab and tixagevimab drug combination; tixagevimab; cilgavimab

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Sponsor terminated the study after review of FDA's request to halt further dosing (30Mar2023) and subjects were terminated prior to 1 year dose 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.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 17, 2022
• Study Start: June 9, 2022
• Primary Completion: October 4, 2023
• Study Completion: October 4, 2023
• Last Updated: October 23, 2024
• Results First Posted: October 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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.

Locations

US (16)