Coronavirus Disease 2019 (COVID-19)
Conditions
Keywords
Coronavirus, COVID-19, AZD7442
Brief summary
To evaluate the safety and tolerability of a single dose of 600 mg AZD7442 administered IV (intravenous) to Chinese adults (including those with stable medical conditions).
Detailed description
A Phase II, randomised, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD7442 for administration to prevent and treat coronavirus disease 2019 (COVID-19) in Chinese adult participants (including healthy participants as well as participants with stable medical conditions), approximately 479 days in duration for each participant.
Interventions
DRUG600 mg AZD7442 IV
Participants will be randomized to receive co-administration of 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) by a single IV infusion.
DRUG600mg placebo IV
Participants will be randomized to receive co-administration of 600mg placebo by a single IV infusion.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults ≥ 18 years 2. Negative results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) 3. Healthy or medically stable participants 4. Contraceptive within 365 days post dosing
Exclusion criteria
1. Medical condition: * Known hypersensitivity to monoclonal antibody (mAb) or investigational product (IP) component. * Acute illness including fever on the day prior to or day of dosing. * Any other significant disease increase the risk to participant study. 2. Laboratory related: * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 2.0 × upper limit of normal (ULN), alkaline phosphatase (ALP) \> 1.5 × ULN, or TBL (total bilirubin) \> 1.5 × ULN (unless due to Gilbert's syndrome). * Serum creatinine \> 176 μmol/L. * Haemoglobin \< 10g/dL. * Platelet count \< 100 × 10\^3/μL. * White blood cell count \< 3.5 × 10\^3/μL or neutrophil count \< 1.5 × 10\^3/μL. * Other laboratory significantly abnormal in the screening panel that, in the opinion of the investigator, will increase participants risk or might confound analysis of study results. 3. COVID-19 infection history/any receipt of mAb indicated for COVID-19. 4. Prior/concomitant treatment: Receipt of any investigational product within 90 days or 5 antibody half-lives (whichever is longer) prior to Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events of Special Interest | recorded from the time of signature of the ICF up to 245 days | Adverse events of special interest are events of scientific and medical interest, specific to the further understanding of the study intervention safety profile, and require close monitoring and rapid communication by the investigators to the sponsor. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentrations of AZD7442 Over Time | recorded from the time of signature of the ICF through the last participant contact. Protocol-specified timepoints include Pre-dose, Day 1, Day 8, Day 31, Day 61, Day 91, Day 181, Day 271, and Day 361. | Serum concentrations for each scheduled time point are summarized based on the PK Analyses Set using descriptive statistics |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AZD7442 AZD7442 600 mg IV | 202 |
| Placebo Placebo Group | 70 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | AZD7442 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 33.67 Years STANDARD_DEVIATION 11.73 | 35.71 Years STANDARD_DEVIATION 12.05 | 34.2 Years STANDARD_DEVIATION 11.8 |
| Age, Customized 18 - 44 years | 170 Participants | 54 Participants | 224 Participants |
| Age, Customized 45 -60 years | 20 Participants | 12 Participants | 32 Participants |
| Age, Customized >60 years | 12 Participants | 4 Participants | 16 Participants |
| Baseline Body Mass Index | 23.84 kg/m^2 STANDARD_DEVIATION 3.14 | 23.91 kg/m^2 STANDARD_DEVIATION 2.96 | 23.86 kg/m^2 STANDARD_DEVIATION 3.09 |
| Baseline Height | 167.50 cm STANDARD_DEVIATION 8.77 | 166.53 cm STANDARD_DEVIATION 7.78 | 167.25 cm STANDARD_DEVIATION 8.53 |
| Baseline Weight | 67.26 kg STANDARD_DEVIATION 11.54 | 66.51 kg STANDARD_DEVIATION 9.91 | 67.07 kg STANDARD_DEVIATION 11.13 |
| COVID-19 vaccination status No, non-vaccinated | 98 Participants | 34 Participants | 132 Participants |
| COVID-19 vaccination status Yes, vaccinated | 104 Participants | 36 Participants | 140 Participants |
| Race/Ethnicity, Customized Asian | 202 Participants | 70 Participants | 272 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 202 Participants | 70 Participants | 272 Participants |
| Sex: Female, Male Female | 62 Participants | 22 Participants | 84 Participants |
| Sex: Female, Male Male | 140 Participants | 48 Participants | 188 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 202 | 0 / 70 |
| other Total, other adverse events | 144 / 202 | 58 / 70 |
| serious Total, serious adverse events | 6 / 202 | 3 / 70 |
Outcome results
Primary
Adverse Events of Special Interest
Adverse events of special interest are events of scientific and medical interest, specific to the further understanding of the study intervention safety profile, and require close monitoring and rapid communication by the investigators to the sponsor.
Time frame: recorded from the time of signature of the ICF up to 245 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD7442 | Adverse Events of Special Interest | 0 Participants |
| Placebo | Adverse Events of Special Interest | 0 Participants |
Secondary
Serum Concentrations of AZD7442 Over Time
Serum concentrations for each scheduled time point are summarized based on the PK Analyses Set using descriptive statistics
Time frame: recorded from the time of signature of the ICF through the last participant contact. Protocol-specified timepoints include Pre-dose, Day 1, Day 8, Day 31, Day 61, Day 91, Day 181, Day 271, and Day 361.
Population: All participants who received AZD7442 and had at least one quantifiable serum PK observation post-dose, with no important protocol deviations thought to impact the analysis of the PK data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZD7442 | Serum Concentrations of AZD7442 Over Time | pre-dose | 0 μg/mL | Standard Deviation 0 |
| AZD7442 | Serum Concentrations of AZD7442 Over Time | Day 1 | 219.7 μg/mL | Standard Deviation 37.81 |
| AZD7442 | Serum Concentrations of AZD7442 Over Time | Day 8 | 136.1 μg/mL | Standard Deviation 26.58 |
| AZD7442 | Serum Concentrations of AZD7442 Over Time | Day 31 | 101.5 μg/mL | Standard Deviation 19.99 |
| AZD7442 | Serum Concentrations of AZD7442 Over Time | Day 61 | 74.60 μg/mL | Standard Deviation 16.08 |
| AZD7442 | Serum Concentrations of AZD7442 Over Time | Day 91 | 55.98 μg/mL | Standard Deviation 12.82 |
| AZD7442 | Serum Concentrations of AZD7442 Over Time | Day 181 | 28.92 μg/mL | Standard Deviation 7.752 |
| AZD7442 | Serum Concentrations of AZD7442 Over Time | Day 271 | 12.74 μg/mL | Standard Deviation 4.186 |
| AZD7442 | Serum Concentrations of AZD7442 Over Time | Day 361 | 5.858 μg/mL | Standard Deviation 2.53 |