Coronavirus Disease 2019 (COVID-19)
Conditions
Keywords
ENDURE
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
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.
Interventions
BIOLOGICALAZD7442 (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.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AEs, SAEs, and AESIs | 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. | To evaluate the safety and tolerability of AZD7442 |
| ADA in Serum Responses | 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. | To evaluate the immunogenicity of AZD7442 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442 |
| 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. | To evaluate the PK of AZD7442 in serum |
| 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. | To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442 |
| 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. | To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442 |
| 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. | To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442 |
Countries
United States
Participant flow
Recruitment details
The participants were screened and randomized from the USA. First subject in was on 09Jun2022 and the last subject last visit was 04Oct2023. 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.
Participants by arm
| Arm | Count |
|---|---|
| AZD7442: 600mg ONCE / 300mg Q3M AZD7442 600 mg intramuscularly (IM) on Day 1 followed by 300 mg IM every 3 months (Q3M) for 12 months. | 124 |
| AZD7442: 1200 mg ONCE / 600mg Q6M AZD7442 1200 mg intravenously (IV) on Day 1 followed by 600 mg IM every 6 months (Q6M) for 12 months. | 124 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Dosing halted by FDA | 96 | 100 |
| Overall Study | Lost to Follow-up | 6 | 6 |
| Overall Study | Not compliant with study visit | 2 | 0 |
| Overall Study | Participant moved | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Signed ICF addendum, however refused procedures | 1 | 0 |
| Overall Study | Withdrawal by Subject | 17 | 19 |
Baseline characteristics
| Characteristic | AZD7442: 600mg ONCE / 300mg Q3M | AZD7442: 1200 mg ONCE / 600mg Q6M | Total |
|---|---|---|---|
| Age, Continuous | 57.3 Years STANDARD_DEVIATION 13.97 | 54.2 Years STANDARD_DEVIATION 14.85 | 55.7 Years STANDARD_DEVIATION 14.47 |
| Age, Customized >=12 - <18 | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized >=18 - <65 | 86 Participants | 98 Participants | 184 Participants |
| Age, Customized >=65 - <75 | 26 Participants | 12 Participants | 38 Participants |
| Age, Customized >=75 - <80 | 9 Participants | 7 Participants | 16 Participants |
| Age, Customized >=80 | 3 Participants | 7 Participants | 10 Participants |
| Body Mass Index (kg/m^2) | 28.66 kg/m^2 STANDARD_DEVIATION 6.884 | 29.66 kg/m^2 STANDARD_DEVIATION 6.582 | 29.16 kg/m^2 STANDARD_DEVIATION 6.74 |
| Body Mass Index (kg/m^2) Category < 25 | 32 Participants | 26 Participants | 58 Participants |
| Body Mass Index (kg/m^2) Category 25 - <30 | 52 Participants | 47 Participants | 99 Participants |
| Body Mass Index (kg/m^2) Category 30 - <35 | 25 Participants | 29 Participants | 54 Participants |
| Body Mass Index (kg/m^2) Category >= 35 | 15 Participants | 22 Participants | 37 Participants |
| Height (cm) | 168.18 cm STANDARD_DEVIATION 10.406 | 167.68 cm STANDARD_DEVIATION 9.946 | 167.93 cm STANDARD_DEVIATION 10.162 |
| Number of pack years (Current or Former) | 18.9 percentages STANDARD_DEVIATION 19.27 | 20.0 percentages STANDARD_DEVIATION 18.74 | 19.3 percentages STANDARD_DEVIATION 18.95 |
| Previous COVID-19 vaccination No | 98 Participants | 105 Participants | 203 Participants |
| Previous COVID-19 vaccination Yes | 26 Participants | 19 Participants | 45 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 20 Participants | 23 Participants | 43 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 63 Participants | 60 Participants | 123 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 60 Participants | 64 Participants | 124 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 96 Participants | 94 Participants | 190 Participants |
| Screening result from Nasopharyngeal swab for SARS-CoV-2 RT-PCR Negative | 124 Participants | 124 Participants | 248 Participants |
| Screening result from Nasopharyngeal swab for SARS-CoV-2 RT-PCR Positive | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 65 Participants | 67 Participants | 132 Participants |
| Sex: Female, Male Male | 59 Participants | 57 Participants | 116 Participants |
| Smoking history Current | 23 Participants | 13 Participants | 36 Participants |
| Smoking history Former | 28 Participants | 24 Participants | 52 Participants |
| Smoking history Never | 73 Participants | 87 Participants | 160 Participants |
| Time since previous COVID-19 vaccination | 107.0 Days | 205.0 Days | 138.0 Days |
| Weight (kg) | 81.17 kg STANDARD_DEVIATION 20.764 | 83.27 kg STANDARD_DEVIATION 19.258 | 82.22 kg STANDARD_DEVIATION 20.013 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 124 | 1 / 124 |
| other Total, other adverse events | 76 / 124 | 58 / 124 |
| serious Total, serious adverse events | 13 / 124 | 10 / 124 |
Outcome results
Primary
ADA in Serum Responses
To evaluate the immunogenicity of AZD7442
Time frame: 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.
Population: ADA Evaluable Analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD7442: 600mg ONCE / 300mg Q3M | ADA in Serum Responses | 1 Participants |
| AZD7442: 1200 mg ONCE / 600mg Q6M | ADA in Serum Responses | 3 Participants |
Primary
AEs, SAEs, and AESIs
To evaluate the safety and tolerability of AZD7442
Time frame: 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.
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD7442: 600mg ONCE / 300mg Q3M | AEs, SAEs, and AESIs | Adverse Events | 84 Participants |
| AZD7442: 600mg ONCE / 300mg Q3M | AEs, SAEs, and AESIs | Serious Adverse Events | 13 Participants |
| AZD7442: 600mg ONCE / 300mg Q3M | AEs, SAEs, and AESIs | Adverse Events of Special Interest | 9 Participants |
| AZD7442: 1200 mg ONCE / 600mg Q6M | AEs, SAEs, and AESIs | Adverse Events of Special Interest | 7 Participants |
| AZD7442: 1200 mg ONCE / 600mg Q6M | AEs, SAEs, and AESIs | Adverse Events | 66 Participants |
| AZD7442: 1200 mg ONCE / 600mg Q6M | AEs, SAEs, and AESIs | Serious Adverse Events | 10 Participants |
Secondary
Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay)
To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time frame: 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.
Population: nAb Evaluable Analysis Set - Pseudo Virus
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 212 fold rise | 10.28 Fold rise | Standard Deviation 6.969 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 121 fold rise | 13.13 Fold rise | Standard Deviation 8.439 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 274 fold rise | 7.06 Fold rise | Standard Deviation 6.133 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 183 fold rise | 7.28 Fold rise | Standard Deviation 6.954 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 365 fold rise | 12.64 Fold rise | Standard Deviation 1.251 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 29 fold rise | 18.02 Fold rise | Standard Deviation 7.081 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 92 fold rise | 7.82 Fold rise | Standard Deviation 7.27 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 365 fold rise | 2.84 Fold rise | Standard Deviation 8.353 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 29 fold rise | 58.84 Fold rise | Standard Deviation 8.473 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 92 fold rise | 20.38 Fold rise | Standard Deviation 8.068 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 183 fold rise | 6.90 Fold rise | Standard Deviation 7.185 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 212 fold rise | 14.44 Fold rise | Standard Deviation 7.457 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 274 fold rise | 8.99 Fold rise | Standard Deviation 8.271 |
Secondary
Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay)
To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time frame: 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.
Population: nAb Evaluable Analysis Set - Authentic Virus
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 212 fold rise | 4.09 Fold rise | Standard Deviation 5.554 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 121 fold rise | 6.53 Fold rise | Standard Deviation 4.928 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 274 fold rise | 1.96 Fold rise | Standard Deviation 4.385 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 183 fold rise | 5.29 Fold rise | Standard Deviation 4.744 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 365 fold rise | 9.97 Fold rise | Standard Deviation 1.093 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 29 fold rise | 6.87 Fold rise | Standard Deviation 4.765 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 92 fold rise | 4.32 Fold rise | Standard Deviation 4.329 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 365 fold rise | 2.00 Fold rise | Standard Deviation 5.343 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 29 fold rise | 16.79 Fold rise | Standard Deviation 6.429 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 92 fold rise | 10.53 Fold rise | Standard Deviation 6.362 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 183 fold rise | 5.43 Fold rise | Standard Deviation 5.122 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 212 fold rise | 5.28 Fold rise | Standard Deviation 6.243 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMFRs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 274 fold rise | 3.08 Fold rise | Standard Deviation 5.82 |
Secondary
Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay)
To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time frame: 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.
Population: nAb Evaluable Analysis Set - Pseudo Virus
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Baseline Titer | 1613.3 Titer | Standard Deviation 7.96 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 29 Titer | 32170.5 Titer | Standard Deviation 1.86 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 92 Titer | 13940.9 Titer | Standard Deviation 1.88 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 121 Titer | 23177.5 Titer | Standard Deviation 1.87 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 183 Titer | 12018.5 Titer | Standard Deviation 1.75 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 212 Titer | 19353.3 Titer | Standard Deviation 1.72 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 274 Titer | 12816.8 Titer | Standard Deviation 1.93 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 365 Titer | 5068.4 Titer | Standard Deviation 1.55 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Baseline Titer | 1735.8 Titer | Standard Deviation 8.35 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 183 Titer | 15554.6 Titer | Standard Deviation 1.8 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 29 Titer | 111726.8 Titer | Standard Deviation 1.75 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 274 Titer | 23583.5 Titer | Standard Deviation 1.91 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 92 Titer | 38048.0 Titer | Standard Deviation 1.73 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 212 Titer | 36519.3 Titer | Standard Deviation 1.67 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs in SARSCoV- 2 nAbs (Pseudo Neutralization Assay) | Day 365 Titer | 7155.4 Titer | Standard Deviation 2.01 |
Secondary
Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay)
To determine anti severe acute respiratory coronavirus-2 neutralizing antibodies (anti-SARS-CoV 2 nAb) levels in serum after administration of AZD7442
Time frame: 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.
Population: nAb Evaluable Analysis Set - Authentic Virus
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Baseline Titer | 203.5 Titer | Standard Deviation 6.43 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 29 Titer | 1442.8 Titer | Standard Deviation 1.88 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 92 Titer | 1052.5 Titer | Standard Deviation 2.22 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 121 Titer | 1520.2 Titer | Standard Deviation 1.97 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 183 Titer | 1209.8 Titer | Standard Deviation 1.95 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 212 Titer | 941.2 Titer | Standard Deviation 2.08 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 274 Titer | 488.5 Titer | Standard Deviation 2.38 |
| AZD7442: 600mg ONCE / 300mg Q3M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 365 Titer | 482.1 Titer | Standard Deviation 1.21 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Baseline Titer | 198.9 Titer | Standard Deviation 7.7 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 183 Titer | 1337.9 Titer | Standard Deviation 2.1 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 29 Titer | 3497.1 Titer | Standard Deviation 2.1 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 274 Titer | 864.7 Titer | Standard Deviation 1.98 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 92 Titer | 2268.6 Titer | Standard Deviation 2.3 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 212 Titer | 1436.1 Titer | Standard Deviation 1.78 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Changes From Baseline in GMTs Values in SARSCoV- 2 nAbs (Wild-type Assay) | Day 365 Titer | 578.9 Titer | Standard Deviation 2.21 |
Secondary
Serum AZD7442 Concentrations
To evaluate the PK of AZD7442 in serum
Time frame: 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.
Population: PK Analysis Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 29 | 40.0381 ug/mL | Geometric Coefficient of Variation 48.7457 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 212 | 36.5360 ug/mL | Geometric Coefficient of Variation 54.5622 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 11 | 45.5626 ug/mL | Geometric Coefficient of Variation 53.9503 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 274 | 24.3601 ug/mL | Geometric Coefficient of Variation 59.3582 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 92 | 27.9754 ug/mL | Geometric Coefficient of Variation 48.9241 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 365 | 21.2009 ug/mL | Geometric Coefficient of Variation 46.2521 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 3 | 30.0089 ug/mL | Geometric Coefficient of Variation 83.7707 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Confirmed Illness 1 Day 1 | 36.2743 ug/mL | Geometric Coefficient of Variation 30.3957 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 121 | 42.1820 ug/mL | Geometric Coefficient of Variation 53.2624 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Confirmed Illness 1 Day 14 | 37.2795 ug/mL | Geometric Coefficient of Variation 25.1834 |
| AZD7442: 600mg ONCE / 300mg Q3M | Serum AZD7442 Concentrations | Day 183 | 23.8985 ug/mL | Geometric Coefficient of Variation 58.4175 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Confirmed Illness 1 Day 14 | 79.1638 ug/mL | Geometric Coefficient of Variation 29.7188 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 3 | 165.1457 ug/mL | Geometric Coefficient of Variation 196.9756 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 11 | 123.2505 ug/mL | Geometric Coefficient of Variation 160.5606 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 29 | 105.8292 ug/mL | Geometric Coefficient of Variation 76.5535 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 92 | 63.0711 ug/mL | Geometric Coefficient of Variation 76.0487 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 183 | 26.4300 ug/mL | Geometric Coefficient of Variation 85.138 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 212 | 60.5211 ug/mL | Geometric Coefficient of Variation 44.6566 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 274 | 38.1694 ug/mL | Geometric Coefficient of Variation 55.8293 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 365 | 17.2078 ug/mL | Geometric Coefficient of Variation 91.1273 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Confirmed Illness 1 Day 1 | 103.0573 ug/mL | Geometric Coefficient of Variation 43.1944 |
| AZD7442: 1200 mg ONCE / 600mg Q6M | Serum AZD7442 Concentrations | Day 1, Post-dose | 285.8539 ug/mL | Geometric Coefficient of Variation 176.0959 |