AZD7442 - a Potential Combination Therapy for the Prevention and Treatment of COVID-19

NCT04507256 | Completed Phase 1 Results DMC

• 2 other identifiers: D8850C000012020-003076-40
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

In this first-in-humans dose escalation study, AZD7442 (AZD8895 + AZD1061) will be evaluated for safety, tolerability, pharmacokinetics, and generation of anti-drug antibodies (ADAs). The study is intended to enable future studies of AZD7442's efficacy in preventing and treating COVID-19.

Conditions

COVID-19

Keywords

Coronavirus; Severe acute respiratory syndrome coronavirus 2; Pharmacokinetics; Safety and tolerability

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious AEs

  The safety and tolerability of AZD7442 administered IV or IM to healthy adult participants 18 to 55 years of age was evaluated.

  From screening day (Day -28) until Follow-up/end of treatment visit (Day 361)

Secondary Outcomes (10)

• Maximum Serum Concentration (Cmax) of AZD7442

  Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)

• Time to Reach Maximum Serum Concentration (Tmax) of AZD7442

  Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)

• Terminal Elimination Half-life (t½λz) of AZD7442

  Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)

• Area Under the Concentration Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of AZD7442

  Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)

• Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of AZD7442

  Day 1 (pre-dose, 8 h), Day 2 (24 h), Day 4 (72 h), Day 6 (120 h), Day 8 (168), Day 15 (336 h), Day 31 (720 h), Day 61 (1440 h), Day 91 (2160 h), Day 151 (3600 h), Day 211 (5040), Day 271 (6480 h), and Day 361 (8640 h)

Study Arms (2)

AZD7442

EXPERIMENTAL

Participants will receive AZD7442 doses across five fixed-dose cohorts via intravenous (IV) infusions (three cohorts will be administered sequentially, and one cohort will receive co-administration of AZD8895 + AZD1061, mixed into a single infusion) and direct gluteal intramuscular (IM) injections (administered sequentially).

Combination Product: AZD7442

Placebo

PLACEBO COMPARATOR

Placebo will be administered to participants across five fixed-dose cohorts similar to the active treatment.

Other: Placebo

Interventions

AZD7442 COMBINATION_PRODUCT

Participants randomized to AZD7442 will be administered dose 1, each in Cohort 1a (IM) and Cohort 1b (IV). Participants in Cohort 2 and 3 will receive AZD7442 (IV) doses 2 and 3, respectively. Participants in Cohort 4 will receive AZD7442 (IV) dose 4.

AZD7442

Placebo OTHER

Participants randomised to placebo will receive the same volume of solution as participants on active treatment.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent and any locally required authorisation obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.
• Negative SARS-CoV-2 qRT-PCR and/or serology tests prior to randomisation.
• Weight ≥ 50 kg and ≤ 110 kg at screening, including a BMI of ≥ 18.0 to ≤ 30.0 kg/m\^2.
• Healthy by medical history, physical examination, and baseline safety laboratory studies, according to the judgement of the PI.
• Electrocardiogram without clinically significant abnormalities at screening.
• Able to complete the Follow-up Period through Day 361.
• Females of childbearing potential who are sexually active with a non-sterilised male partner must have used a highly effective method of contraception for at least 28 days prior to dosing with IMP and must agree to continue using such precautions until the Final Follow-up Visit. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

You may not qualify if:

• Known hypersensitivity to any component of the IMP.
• History of allergic disease or reactions likely to be exacerbated by any component of the IMP.
• Previous hypersensitivity, infusion-related reaction or severe adverse reaction following administration of a mAbs.
• Acute (time-limited) illness, including fever above 37.5°C (99.5 °F), on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves within the 27-day Screening Period or may be rescreened once.
• Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 2 months prior to screening.
• Receipt of immunoglobulin or blood products within 6 months prior to screening.
• SARS CoV-2 or COVID-19:
• Participants with any confirmed current or previous COVID-19 infection before randomisation.
• Participant has clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnoea, sore throat, fatigue or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
• Any prior receipt of investigational or licensed vaccine indicated for the prevention of SARS CoV-2 or COVID-19 or expected receipt during the period of study follow up.
• Receipt of any IMP in the preceding 90 days or expected receipt of IMP during the period of study follow-up, or concurrent participation in another interventional study.
• Previous receipt of a mAb within 6 months, or five antibody half lives (whichever is longer), prior to study start.
• Immunodeficiency due to illness, including Human immunodeficiency virus (HIV) infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening. HIV testing must be negative at screening.
• Either history of active infection with hepatitis B or C or positive test for hepatitis C or for hepatitis B surface antigen at screening.
• History of infection with SARS or MERS.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Harrow, HA1 3UJ, United Kingdom

Location

Related Publications (2)

• Forte-Soto P, Albayaty M, Brooks D, Arends RH, Tillinghast J, Aksyuk AA, Bouquet J, Chen C, Gebre A, Kubiak RJ, Pilla Reddy V, Seegobin S, Streicher K, Templeton A, Esser MT. Safety, Tolerability and Pharmacokinetics of Half-Life Extended Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab-Cilgavimab) in Healthy Adults. J Infect Dis. 2023 May 12;227(10):1153-1163. doi: 10.1093/infdis/jiad014.

  PMID: 36683419 DERIVED

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

Related Links

• Redacted CSR synopsis
• Redacted CSP and SAP

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

cilgavimab and tixagevimab drug combination

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Global Clinical Head
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Pablo Forte Soto, MD, MSc, PhD

  Parexel EPCU (London)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The study will be blinded for all placebo controlled dose groups, ie, the Principal Investigator (PI), all clinical staff involved in the clinical study, the participants, and the study monitor will remain blinded, unless safety concerns or a regulatory requirement necessitate unblinding.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2020
• First Posted: August 11, 2020
• Study Start: August 18, 2020
• Primary Completion: October 19, 2021
• Study Completion: October 19, 2021
• Last Updated: October 18, 2024
• Results First Posted: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• 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 refer 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

GB (1)