COVID-19
Conditions
Keywords
Post exposure COVID-19
Brief summary
This study will assess the efficacy of AZD7442 for the post-exposure prophylaxis of COVID-19 in Adults.
Detailed description
SARS-CoV-2 is the causative agent of the ongoing COVID-19 pandemic that, as of 29 September 2020, has resulted in a high death toll to date. Unlike the majority of coronaviruses that cause mild disease in humans and animals, SARS-CoV-2 can replicate in the lower respiratory tract to cause acute respiratory distress syndrome and fatal pneumonia. Effective interventions to prevent or treat COVID-19 remain limited in number and clinical experience is limited. Clinical management is limited to supportive care, consequently overwhelming resources of healthcare systems around the world. As a response to the ongoing pandemic, AstraZeneca is developing mAbs to the SARS-CoV-2 S protein. The SARS-CoV-2 spike protein contains the virus's RBD, which enables the virus to bind to receptors on human cells. By targeting this region of the virus's spike protein, antibodies can block the virus's attachment to human cells, and, therefore, is expected to block infection. Amino acid substitutions have been introduced into the antibodies to both extend their half-lives, which should prolong their potential prophylactic benefit, and decrease Fc effector function in order to decrease the potential risk of antibody-dependent enhancement of disease. AZD7442, a combination of 2 of these mAbs (AZD8895 and AZD1061), is being evaluated for administration to prevent and/or treat COVID-19. There is currently one ongoing Phase I study with AZD7442.
Interventions
DRUGAZD7442
Single dose (× 2 IM injections) of 300 mg of AZD7442 on Day 1.
DRUGPlacebo
Single dose (× 2 IM injections) of saline placebo on Day 1.
Sponsors
Iqvia Pty Ltd
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. ≥ 18 years of age at the time of signing the informed consent 2. Adults with potential exposure, within 8 days, to a specific identified individual with laboratory-confirmed SARS-COV-2 infection, symptomatic or asymptomatic 3. Participants must not have had COVID-19 symptoms within 10 days of dosing 4. Negative result from point of care SARS-CoV-2 serology test at screening 5. Contraception used by women of childbearing potential, condom by men 6. Able to understand and comply with study requirements/procedures based on the assessment of the investigator
Exclusion criteria
1. History of laboratory-confirmed SARS-CoV-2 infection or SARS-CoV-2 seropositivity at screening. 2. History of infection with severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). 3. Known history of allergy or reaction to any component of the study drug formulation. 4. Previous hypersensitivity, infusion-related reaction, or severe adverse reaction following administration of a mAb. 5. Any prior receipt of investigational or licensed vaccine or other mAb/biologic indicated for the prevention of SARS-CoV-2 or COVID-19 or expected receipt during the period of study follow up. 6. Clinically significant bleeding disorder or prior history of significant bleeding or bruising following IM injections or venipuncture. 7. Any other significant disease, disorder, or finding that, in the judgement of the investigator, 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. 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. 9. Currently pregnant or breast feeding. 10. Blood drawn in excess of a total of 450 mL (1 unit) for any reason within 30 days prior to randomization. 11. 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. 12. 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 |
|---|---|---|
| Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness | Planned to be evaluated through Day 183, however, the number of participants required was achieved 127 days after the study start date | To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19 |
| AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | 457 Days | — |
Secondary
| Measure | Time frame |
|---|---|
| The Incidence of COVID-19-related Death Occurring After Dosing With IMP | 366 Days |
| The Incidence of All-cause Mortality Occurring After Dosing With IMP | 366 Days |
| The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP | 183 Days |
| Incidence of ADA to AZD7442 in Serum | 457 Days |
| Serum AZD7442 Concentrations, PK Parameters | 457 Days |
| The Incidence of Participants Who Have a Post-treatment Response (Negative at Baseline to Positive at Any Time Post-baseline) for SARSCoV- 2 Nucleocapsid Antibodies | 366 Days |
Countries
United Kingdom, United States
Participant flow
Recruitment details
Target sample size was 1125. As this was a multi-site study there was a lag on the information of the number of participants recruited, hence we ended up with a population slightly over 1125 (N=1131).
Participants by arm
| Arm | Count |
|---|---|
| AZD7442 Single dose 300 mg IM (AZD8895 and AZD1061) | 749 |
| Placebo Saline Placebo | 372 |
| Total | 1,121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 82 | 38 |
| Overall Study | Not specified elsewhere | 8 | 6 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 37 | 24 |
Baseline characteristics
| Characteristic | Total | Placebo | AZD7442 |
|---|---|---|---|
| Age, Continuous | 46.40 Years STANDARD_DEVIATION 15.89 | 45.97 Years STANDARD_DEVIATION 16.2 | 46.62 Years STANDARD_DEVIATION 15.74 |
| Age, Customized | 48.0 Years | 47.00 Years | 48.00 Years |
| Any COVID-19 comorbidities at baseline MISSING | 493 Participants | 162 Participants | 331 Participants |
| Any COVID-19 comorbidities at baseline Yes | 628 Participants | 210 Participants | 418 Participants |
| Any high risk for severe COVID-19 at baseline MISSING | 392 Participants | 129 Participants | 263 Participants |
| Any high risk for severe COVID-19 at baseline Yes | 729 Participants | 243 Participants | 486 Participants |
| Baseline BMI (kg/m^2) | 29.67 kg/m^2 STANDARD_DEVIATION 6.67 | 29.80 kg/m^2 STANDARD_DEVIATION 6.68 | 29.60 kg/m^2 STANDARD_DEVIATION 6.67 |
| Height | 168.5 cm STANDARD_DEVIATION 10.48 | 168.57 cm STANDARD_DEVIATION 10.32 | 168.43 cm STANDARD_DEVIATION 10.56 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 7 Participants | 1 Participants | 6 Participants |
| Race/Ethnicity, Customized Asian | 28 Participants | 13 Participants | 15 Participants |
| Race/Ethnicity, Customized Black or African American | 112 Participants | 36 Participants | 76 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 645 Participants | 210 Participants | 435 Participants |
| Race/Ethnicity, Customized Multiple | 8 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 458 Participants | 159 Participants | 299 Participants |
| Race/Ethnicity, Customized Not reported | 18 Participants | 3 Participants | 15 Participants |
| Race/Ethnicity, Customized Unknown | 6 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 942 Participants | 314 Participants | 628 Participants |
| SARS-CoV-2 status at baseline MISSING | 95 Participants | 31 Participants | 64 Participants |
| SARS-CoV-2 status at baseline Negative | 978 Participants | 327 Participants | 651 Participants |
| SARS-CoV-2 status at baseline Positive | 48 Participants | 14 Participants | 34 Participants |
| Sex: Female, Male Female | 557 Participants | 182 Participants | 375 Participants |
| Sex: Female, Male Male | 564 Participants | 190 Participants | 374 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 749 | 2 / 372 |
| other Total, other adverse events | 345 / 749 | 191 / 372 |
| serious Total, serious adverse events | 20 / 749 | 16 / 372 |
Outcome results
Primary
AEs, SAEs, MAAEs, and AESIs Post Dose of IMP
Time frame: 457 Days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD7442 | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Adverse Events of Special Interest | 4 Participants |
| AZD7442 | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Non-serious Adverse Event | 345 Participants |
| AZD7442 | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Serious Adverse Events | 20 Participants |
| AZD7442 | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Medically Attended Adverse Events | 95 Participants |
| AZD7442 | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Any Adverse Event | 348 Participants |
| Placebo | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Medically Attended Adverse Events | 52 Participants |
| Placebo | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Adverse Events of Special Interest | 4 Participants |
| Placebo | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Non-serious Adverse Event | 191 Participants |
| Placebo | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Any Adverse Event | 193 Participants |
| Placebo | AEs, SAEs, MAAEs, and AESIs Post Dose of IMP | Serious Adverse Events | 16 Participants |
Primary
Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness
To estimate the efficacy of a single IM dose of AZD7442 compared to placebo for the prevention of COVID-19
Time frame: Planned to be evaluated through Day 183, however, the number of participants required was achieved 127 days after the study start date
Population: All randomized participants who received at least one dose of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD7442 | Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness | Primary Analysis | 23 Participants |
| AZD7442 | Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness | Final analysis | 28 Participants |
| Placebo | Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness | Primary Analysis | 17 Participants |
| Placebo | Number of Participants With First Case of SARS-CoV-2 RT-PCR Positive Symptomatic Illness | Final analysis | 24 Participants |
p-value: 0.21295% CI: [-25.92, 64.68]Poisson regression
p-value: 0.04495% CI: [1.4, 67.37]Poisson regression
Secondary
Incidence of ADA to AZD7442 in Serum
Time frame: 457 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD7442 | Incidence of ADA to AZD7442 in Serum | 110 Participants |
| Placebo | Incidence of ADA to AZD7442 in Serum | 6 Participants |
Secondary
Serum AZD7442 Concentrations, PK Parameters
Time frame: 457 Days
Population: Only AZD7442 arm samples have been analysed for PK concentrations. Baseline and Day 457 were not calculated due to lot of missing samples or concentrations \< LLOQ
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD7442 | Serum AZD7442 Concentrations, PK Parameters | Day 8 | 10.028 µg/mL | Geometric Coefficient of Variation 110.166 |
| AZD7442 | Serum AZD7442 Concentrations, PK Parameters | Day 29 | 11.718 µg/mL | Geometric Coefficient of Variation 72.721 |
| AZD7442 | Serum AZD7442 Concentrations, PK Parameters | Day 58 | 9.420 µg/mL | Geometric Coefficient of Variation 75.16 |
| AZD7442 | Serum AZD7442 Concentrations, PK Parameters | Day 92 | 7.183 µg/mL | Geometric Coefficient of Variation 81.706 |
| AZD7442 | Serum AZD7442 Concentrations, PK Parameters | Day 183 | 2.975 µg/mL | Geometric Coefficient of Variation 79.694 |
| AZD7442 | Serum AZD7442 Concentrations, PK Parameters | Day 366 | 0.696 µg/mL | Geometric Coefficient of Variation 63.725 |
Secondary
The Incidence of All-cause Mortality Occurring After Dosing With IMP
Time frame: 366 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD7442 | The Incidence of All-cause Mortality Occurring After Dosing With IMP | 3 Participants |
| Placebo | The Incidence of All-cause Mortality Occurring After Dosing With IMP | 2 Participants |
p-value: 0.74495% CI: [-343.53, 87.57]Poisson regression
Secondary
The Incidence of COVID-19-related Death Occurring After Dosing With IMP
Time frame: 366 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD7442 | The Incidence of COVID-19-related Death Occurring After Dosing With IMP | 0 Participants |
| Placebo | The Incidence of COVID-19-related Death Occurring After Dosing With IMP | 0 Participants |
Secondary
The Incidence of Participants Who Have a Post-treatment Response (Negative at Baseline to Positive at Any Time Post-baseline) for SARSCoV- 2 Nucleocapsid Antibodies
Time frame: 366 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD7442 | The Incidence of Participants Who Have a Post-treatment Response (Negative at Baseline to Positive at Any Time Post-baseline) for SARSCoV- 2 Nucleocapsid Antibodies | 173 Participants |
| Placebo | The Incidence of Participants Who Have a Post-treatment Response (Negative at Baseline to Positive at Any Time Post-baseline) for SARSCoV- 2 Nucleocapsid Antibodies | 98 Participants |
p-value: 0.16395% CI: [-6.23, 30.21]Poisson regression
Secondary
The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP
Time frame: 183 Days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD7442 | The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP | Primary analysis | 0 Participants |
| AZD7442 | The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP | Final Analysis | 0 Participants |
| Placebo | The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP | Primary analysis | 1 Participants |
| Placebo | The Incidence of SARS-CoV-2 RT-PCR-positive Severe or Critical Symptomatic Illness Occurring After Dosing With IMP | Final Analysis | 1 Participants |
p-value: 0.664Poisson regression