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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003076-40 | EudraCT Number |
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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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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.
This is a Phase I, first time in human, randomised, double-blind, placebo-controlled, and dose escalation study.
The study will comprise of:
The study will be conducted at a single study centre in United Kingdom.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
|
| Placebo | Placebo Comparator | Placebo will be administered to participants across five fixed-dose cohorts similar to the active treatment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Serum Concentration (Cmax) of AZD7442 | The single dose Cmax of AZD7442 and of the individual monoclonal antibodies (mAbs) in serum were evaluated. | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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.
Receipt of immunoglobulin or blood products within 6 months prior to screening.
SARS CoV-2 or COVID-19:
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).
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| Name | Affiliation | Role |
|---|---|---|
| Pablo Forte Soto, MD, MSc, PhD | Parexel EPCU (London) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Harrow | HA1 3UJ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36683419 | Derived | 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. | |
| 34473343 |
| Label | URL |
|---|---|
| Redacted CSR synopsis | View source |
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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.
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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.
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.
Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. A washout period was not included in this study.
A total of 60 healthy participants were enrolled at a single study center in the United Kingdom (UK) from 18 August 2020 to 19 0ctober 2021.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pooled Placebo | Participants received single intravenous infusion (IV) or intramuscular injection (IM) of placebo. |
| FG001 | AZD7442 300 mg, IM | Participants received 300 mg of AZD7442 (AZD8895 + AZD1061) via intramuscular injection (IM) administered in 2 sequential injections, starting with 150 mg AZD8895 and followed by 150 mg AZD1061. |
| FG002 | AZD7442 300 mg, IV | Participants received 300 mg of AZD7442 (AZD8895 + AZD1061) via intravenous infusion (IV) administered in 2 sequential infusions, starting with 150 mg AZD8895 and followed by 150 mg AZD1061. |
| FG003 | AZD7442 1000 mg, IV | Participants received 1000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion administered in 2 sequential infusions, starting with 500 mg AZD8895 and followed by 500 mg AZD1061. |
| FG004 | AZD7442 3000 mg, IV | Participants received 3000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion administered in 2 sequential infusions, starting with 1500 mg AZD8895 and followed by 1500 mg AZD1061. |
| FG005 | AZD7442 3000 mg, IV Co-administered | Participants received 3000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion, the investigational medicinal product (IMP) was co-administered as a single IV infusion containing both (1500 mg of AZD8895 and 1500 mg of AZD1061). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The randomized set consisted of all participants randomized into the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Pooled Placebo | Participants received single intravenous infusion (IV) or intramuscular injection (IM) of placebo. |
| BG001 | AZD7442 300 mg, IM | Participants received 300 mg of AZD7442 (AZD8895 + AZD1061) via intramuscular injection (IM) administered in 2 sequential injections, starting with 150 mg AZD8895 and followed by 150 mg AZD1061. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety analysis set included all participants who were randomized and received any amount of AZD7442. | Posted | Count of Participants | Participants | From screening day (Day -28) until Follow-up/end of treatment visit (Day 361) |
|
From screening day (Day -28) until Follow-up/end of treatment visit (Day 361)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pooled Placebo | Participants received single intravenous infusion (IV) or intramuscular injection (IM) of placebo. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Head | AstraZeneca | 1-877-240-9479 | information.center@astrazeneca.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 19, 2021 | Apr 15, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D018352 | Coronavirus Infections |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000714168 | cilgavimab and tixagevimab drug combination |
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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.
|
| Placebo | Other | Participants randomised to placebo will receive the same volume of solution as participants on active treatment. |
|
| Time to Reach Maximum Serum Concentration (Tmax) of AZD7442 | The single dose tmax of AZD7442 and of the individual mAbs in serum was evaluated | 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 | The single dose t½λz of AZD7442 and of the individual mAbs in serum was evaluated. | 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 | The single dose AUClast of AZD7442 and of the individual mAbs in serum was evaluated. | 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 | 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. | 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) |
| Systemic Clearance (CL) of AZD7442 IV Infusion | The single dose CL of AZD7442 and of the individual mAbs in serum was evaluated. | 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) |
| 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. | 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) |
| 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. | 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) |
| 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. | 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) |
| Percentage of Participants Who Have Positive Antidrug Antibodies (ADA) of AZD8895 and AZD1061 | The ADA response to AZD7442 in serum was evaluated. | Day 361 (Post dose) |
| 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. |
| Redacted CSP and SAP | View source |
| BG002 | AZD7442 300 mg, IV | Participants received 300 mg of AZD7442 (AZD8895 + AZD1061) via intravenous infusion (IV) administered in 2 sequential infusions, starting with 150 mg AZD8895 and followed by 150 mg AZD1061. |
| BG003 | AZD7442 1000 mg, IV | Participants received 1000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion administered in 2 sequential infusions, starting with 500 mg AZD8895 and followed by 500 mg AZD1061. |
| BG004 | AZD7442 3000 mg, IV | Participants received 3000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion administered in 2 sequential infusions, starting with 1500 mg AZD8895 and followed by 1500 mg AZD1061. |
| BG005 | AZD7442 3000 mg, IV Co-administered | Participants received 3000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion, the investigational medicinal product (IMP) was co-administered as a single IV infusion containing both (1500 mg of AZD8895 and 1500 mg of AZD1061). |
| BG006 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | AZD7442 300 mg, IV | Participants received 300 mg of AZD7442 (AZD8895 + AZD1061) via intravenous infusion (IV) administered in 2 sequential infusions, starting with 150 mg AZD8895 and followed by 150 mg AZD1061. |
| OG003 | AZD7442 1000 mg, IV | Participants received 1000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion administered in 2 sequential infusions, starting with 500 mg AZD8895 and followed by 500 mg AZD1061. |
| OG004 | AZD7442 3000 mg, IV | Participants received 3000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion administered in 2 sequential infusions, starting with 1500 mg AZD8895 and followed by 1500 mg AZD1061. |
| OG005 | AZD7442 3000 mg, IV Co-administered | Participants received 3000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion, the investigational medicinal product (IMP) was co-administered as a single IV infusion containing both (1500 mg of AZD8895 and 1500 mg of AZD1061). |
|
|
| Secondary | Maximum Serum Concentration (Cmax) of AZD7442 | The single dose Cmax of AZD7442 and of the individual monoclonal antibodies (mAbs) in serum were evaluated. | The Pharmacokinetic (PK) analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | μg/mL (microgram per milliliter) | 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) |
|
|
|
| Secondary | Time to Reach Maximum Serum Concentration (Tmax) of AZD7442 | The single dose tmax of AZD7442 and of the individual mAbs in serum was evaluated | The PK analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. | Posted | Median | Full Range | Day | 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) |
|
|
|
| Secondary | Terminal Elimination Half-life (t½λz) of AZD7442 | The single dose t½λz of AZD7442 and of the individual mAbs in serum was evaluated. | The PK analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | Day | 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) |
|
|
|
| Secondary | 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. | The PK analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | day*μg/mL (microgram per milliliter) | 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) |
|
|
|
| Secondary | 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. | The PK analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | day*ug/mL (microgram per milliliter) | 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) |
|
|
|
|
| Secondary | Systemic Clearance (CL) of AZD7442 IV Infusion | The single dose CL of AZD7442 and of the individual mAbs in serum was evaluated. | The PK analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. It was pre-specified in the statistical analysis plan (SAP) and clinical study protocol (CSP) to report CL for only arms receiving IV infusion. | Posted | Mean | Standard Deviation | L (Litre)/day | 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) |
|
|
|
| Secondary | 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. | The PK analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. It was pre-specified in the SAP and CSP to report CL/F for only arm receiving IM injection. | Posted | Mean | Standard Deviation | L (Litre)/day | 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) |
|
|
|
| Secondary | 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. | The PK analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. | Posted | Mean | Standard Deviation | L (Litre) | 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) |
|
|
|
| Secondary | 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. | The PK analysis set consisted of all participants in the safety analysis set who received AZD7442 and who had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. It was pre-specified in the SAP and CSP to report Vss for only arms receiving IV infusion. | Posted | Mean | Standard Deviation | L (Litre) | 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) |
|
|
|
| Secondary | Percentage of Participants Who Have Positive Antidrug Antibodies (ADA) of AZD8895 and AZD1061 | The ADA response to AZD7442 in serum was evaluated. | Safety analysis set included all participants who were randomized and received any amount of AZD7442. | Posted | Count of Participants | Participants | Day 361 (Post dose) |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 8 |
| 10 |
| EG001 | AZD7442 300 mg, IM | Participants received 300 mg of AZD7442 (AZD8895 + AZD1061) via intramuscular injection (IM) administered in 2 sequential injections, starting with 150 mg AZD8895 and followed by 150 mg AZD1061. | 0 | 10 | 0 | 10 | 2 | 10 |
| EG002 | AZD7442 300 mg, IV | Participants received 300 mg of AZD7442 (AZD8895 + AZD1061) via intravenous infusion (IV) administered in 2 sequential infusions, starting with 150 mg AZD8895 and followed by 150 mg AZD1061. | 0 | 10 | 0 | 10 | 5 | 10 |
| EG003 | AZD7442 1000 mg, IV | Participants received 1000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion administered in 2 sequential infusions, starting with 500 mg AZD8895 and followed by 500 mg AZD1061. | 0 | 10 | 0 | 10 | 6 | 10 |
| EG004 | AZD7442 3000 mg, IV | Participants received 3000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion administered in 2 sequential infusions, starting with 1500 mg AZD8895 and followed by 1500 mg AZD1061. | 0 | 10 | 0 | 10 | 7 | 10 |
| EG005 | AZD7442 3000 mg, IV Co-administered | Participants received 3000 mg of AZD7442 (AZD8895 + AZD1061) via IV infusion, the investigational medicinal product (IMP) was co-administered as a single IV infusion containing both (1500 mg of AZD8895 and 1500 mg of AZD1061). | 0 | 10 | 0 | 10 | 6 | 10 |
| Dizziness | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Coronavirus infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Nail infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Vulvovaginal candidiasis | Infections and infestations | MedDRA version 24.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Application site irritation | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Energy increased | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Vessel puncture site pain | General disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Injury | Injury, poisoning and procedural complications | MedDRA version 24.0 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Heavy menstrual bleeding | Reproductive system and breast disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Myxoid cyst | Skin and subcutaneous tissue disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Tooth repair | Surgical and medical procedures | MedDRA version 24.0 | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA version 24.0 | Non-systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| AZD1061 |
|
| AZD1061 |
|
| AZD1061 |
|
| AZD1061 |
|
| AZD1061 |
|
Bioavailability of AZD1061 at the end of study (Day 361) |
| Ratio of geometric mean AUCinf |
| 65.02 |
The bioavailability of AZD7442 Dose 1 administered by IM was, calculated as the ratio of geometric mean AUCinf after IM to IV, for mAb AZD1061. |
| Other |
Bioavailability |
| AZD1061 |
|
| AZD1061 |
|
| AZD1061 |
|
| AZD1061 |
|