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COVID-19Phase 1NCT04507256

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

A Phase 1 study testing AZD7442 in people with COVID-19, run by AstraZeneca at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
COVID-19
What is being tested?
AZD7442
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
60 participants
Where
1 siteUnited Kingdom
Study dates
18 Aug 2020to 19 Oct 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
  • Any drug therapy within 7 days prior to Day 1 (except contraceptives or a single use of acetaminophen, aspirin, antihistamine, or combination over the counter (OTC) product that contains acetaminophen with an antihistamine, or OTC nonsteroidal anti-inflammatory agent at a dose equal to or lower than that recommended on the package). Vitamins and other nutritional supplements that are not newly introduced, ie, have been taken for at least 30 days prior to enrolment, are not exclusionary.
  • Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 2 months prior to screening.
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  • 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.
  • Aspartate aminotransferase, ALT, or serum creatinine above the ULN; bilirubin and ALP >1.5 × ULN.
  • Haemoglobin or platelet count below the LLN at screening. White blood cell or neutrophil count outside normal references ranges.
  • History of malignancy.
  • Any laboratory value in the screening panel that, in the opinion of the PI, is clinically significant or might confound analysis of study results.
  • Pregnant or nursing female.
  • History of alcohol or drug abuse within the past 2 years that, according to the PI, might affect assessments of safety or ability of participant to comply with all study requirements OR positive urine drug or alcohol screening.
  • Any condition that, in the opinion of the PI, might compromise participant safety or interfere with evaluation of the IMP or interpretation of participant safety or study results.
  • Employees of the sponsor, clinical study site, or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
  • Absence of suitable veins for blood sampling (IM and IV cohorts) and administration of IMP (IV cohorts).

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • Research Site

    Harrow, HA1 3UJ

Other trials in United Kingdom

About this study

Official title: A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of AZD7442 in Healthy Adults

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.

Read the detailed description

This is a Phase I, first time in human, randomised, double-blind, placebo-controlled, and dose escalation study.

The study will comprise of:

  1. A Screening Period of up to 27 days (Day -28 through Day -2);
  2. A Treatment Period during which participants will be resident at the Clinical Unit from Day -1, 1 day before Investigational Medicinal Product (IMP) administration (on Day 1) until at least 24 hours after IMP administration, will be discharged on Day 2 after all safety evaluations have been completed, and
  3. A Follow up Period lasting 360 days (through to Day 361) after the IMP dose.

The study will be conducted at a single study centre in United Kingdom.

Conditions
COVID-19
Being tested
AZD7442, Placebo
Keywords
Coronavirus, Severe acute respiratory syndrome coronavirus 2, Pharmacokinetics, Safety and tolerability
Medical subject headings
COVID-19, Coronavirus Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD7442Combination 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.

  • PlaceboOther

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

Study groups in NCT04507256
Study groupRoleWhat they receive
AZD7442ExperimentalParticipants 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).
Receives: Combination Product: AZD7442
PlaceboPlacebo comparatorPlacebo will be administered to participants across five fixed-dose cohorts similar to the active treatment.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (10)

  1. Maximum Serum Concentration (Cmax) of AZD7442

    The single dose Cmax of AZD7442 and of the individual monoclonal antibodies (mAbs) in serum were evaluated.

    Measured: 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)

  2. Time to Reach Maximum Serum Concentration (Tmax) of AZD7442

    The single dose tmax of AZD7442 and of the individual mAbs in serum was evaluated

    Measured: 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)

  3. Terminal Elimination Half-life (t½λz) of AZD7442

    The single dose t½λz of AZD7442 and of the individual mAbs in serum was evaluated.

    Measured: 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)

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

    The single dose AUClast of AZD7442 and of the individual mAbs in serum was evaluated.

    Measured: 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)

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

    The single dose AUCinf of AZD7442 and of the individual mAbs in serum was evaluated. The bioavailability (F) of AZD7442 Dose 1 administered by IM was calculated as the ratio of geometric mean AUCinf after IM to IV, for mAb AZD8895 and mAb AZD1061 is also presented.

    Measured: 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)

  6. Systemic Clearance (CL) of AZD7442 IV Infusion

    The single dose CL of AZD7442 and of the individual mAbs in serum was evaluated.

    Measured: 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)

  7. Apparent Total Clearance (CL/F) of AZD7442 IM Injection

    The single dose CL/F of AZD7442 and of the individual mAbs in serum was evaluated.

    Measured: 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)

  8. Apparent Volume of Distribution at Terminal Phase (Vz/F) of AZD7442

    The single dose Vz/F of AZD7442 and of the individual mAbs in serum was evaluated.

    Measured: 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)

  9. Volume of Distribution at Steady State (Vss) of AZD7442 IV Infusion

    The single dose Vss of AZD7442 and of the individual mAbs in serum was evaluated.

    Measured: 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)

  10. Percentage of Participants Who Have Positive Antidrug Antibodies (ADA) of AZD8895 and AZD1061

    The ADA response to AZD7442 in serum was evaluated.

    Measured: Day 361 (Post dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2020
  2. Study start18 Aug 2020
  3. Primary completion19 Oct 2021
  4. Study completion19 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04507256
Sponsor's protocol ID
D8850C00001
Other IDs
2020-003076-40
Status last verified
Oct 2024
First submitted
7 Aug 2020
Last updated
18 Oct 2024
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests 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.

Publications

  • 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.

    PubMed 36683419

  • 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.

    PubMed 34473343

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD7442 in people with COVID-19, run by AstraZeneca at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Adverse Events (AEs) and Serious AEs (time frame: From screening day (Day -28) until Follow-up/end of treatment visit (Day 361)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04507256, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2024.

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