COVID-19, SARS-CoV-2
Conditions
Keywords
Pre-exposure Prophylaxis of COVID-19
Brief summary
AZD3152, a single mAb, is being developed to have broad neutralizing activity across known SARS-CoV-2 variants of concern for pre-exposure prophylaxis of COVID-19. The aim of the Phase II study is to evaluate the safety, neutralizing activity and efficacy of AZD3152 for pre exposure prophylaxis of COVID-19
Detailed description
Phase II study to assess the safety, neutralizing activity and efficacy of one dose of AZD3152 compared with one dose of placebo in adults with immunocompromised conditions, including comorbidities contributing to weakened immunity, thereby increasing the risk of COVID-19 progression up to severe grade.
Interventions
BIOLOGICALBiological: AZD3152
300 mg single dose of AZD3152 IM
BIOLOGICALBiological: Placebo
Single dose of Placebo IM (0.9% sodium chloride)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a Phase II Randomized, Double-blind Study to Evaluate the Safety, Neutralizing Activity and Efficacy of AZD3152 for Pre-exposure Prophylaxis of COVID-19 in adult participants. Approximately 116 participants in Russia will be randomized at up to 10 study sites in a ratio of 3:1 to either AZD3152 or placebo administered IM.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be 18 years of age or older at the time of signing the informed consent. * Weight ≥ 45 kg at Visit 1. * Participants must satisfy at least 1 of the following risk factors at enrollment: 1. Obese, ie, BMI ≥ 30 2. Congestive heart failure 3. Chronic obstructive pulmonary disease 4. Chronic kidney disease 5. Intolerant of vaccine 6. Immunocompromised state (one of the following risk factors ): 1. Have cancer 2. Have solid organ transplant or a hematopoietic stem cell transplant 3. Are actively taking immunosuppressive medicines 4. Received chimeric antigen receptor T-cell therapy 5. Within 1 year of receiving B-cell depleting therapies 6. Have a moderate or severe primary immunodeficiency * Medically stable * WOCBP must not be pregnant or lactating and must use a highly effective method of contraception
Exclusion criteria
* Known hypersensitivity to any component of the study intervention * Previous hypersensitivity or severe adverse reaction following administration of a mAb * Acute or febrile infection prior to dosing * Has HIV infection * Receipt of any convalescent COVID-19 plasma treatment, mAb against SARS-CoV-2 , COVID-19 vaccine within 6 months * COVID-19 antiviral prophylaxis within at least 2 weeks * COVID-19 case within 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | up to Day 181 | The safety profile will be evaluated using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | up to Day 181 | GMT of nAbs against SARS-CoV-2 emerging dominant variant(s) circulating during the course of the study (measured in RU local laboratory) |
| Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | up to Day 181 | GMFR (from baseline) of nAb titers against SARS-CoV-2 emerging dominant variant(s) circulating during the course of the study (measured in RU local laboratory) |
| Incidence of a Post-treatment Symptomatic COVID-19 Case | up to Day 181 | Incidence of a post-treatment symptomatic COVID-19 case (negative RT-PCR at baseline to positive RT-PCR or positive antigen test at any time up to 6 months AND symptoms specified in the modified WHO definition of symptomatic COVID-19). |
Countries
Russia
Participant flow
Recruitment details
\[Not Specified\]
Pre-assignment details
\[Not Specified\]
Participants by arm
| Arm | Count |
|---|---|
| AZD3152 AZD3152 300 mg | 87 |
| Placebo Saline Placebo | 29 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | AZD3152 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55.6 Years STANDARD_DEVIATION 12.61 | 58.2 Years STANDARD_DEVIATION 11.78 | 56.2 Years STANDARD_DEVIATION 12.41 |
| Age, Customized >= 18 to <60 years | 52 Participants | 15 Participants | 67 Participants |
| Age, Customized >=60 years | 35 Participants | 14 Participants | 49 Participants |
| Any COVID-19 comorbidities at baseline Missing | 0 Participants | 0 Participants | 0 Participants |
| Any COVID-19 comorbidities at baseline Yes | 87 Participants | 29 Participants | 116 Participants |
| Any high risk for severe COVID-19 Missing | 0 Participants | 0 Participants | 0 Participants |
| Any high risk for severe COVID-19 Yes | 87 Participants | 29 Participants | 116 Participants |
| Baseline BMI | 28.7 kg/m^2 STANDARD_DEVIATION 6.08 | 27.8 kg/m^2 STANDARD_DEVIATION 5.3 | 28.5 kg/m^2 STANDARD_DEVIATION 5.89 |
| Height | 171.0 cm STANDARD_DEVIATION 9.39 | 170.7 cm STANDARD_DEVIATION 8.8 | 170.9 cm STANDARD_DEVIATION 9.21 |
| Previous COVID-19 vaccinations | 56 Participants | 13 Participants | 69 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 4 Participants | 1 Participants | 5 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 83 Participants | 28 Participants | 111 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 86 Participants | 29 Participants | 115 Participants |
| SARS-CoV-2 status at baseline Missing | 0 Participants | 0 Participants | 0 Participants |
| SARS-CoV-2 status at baseline Negative | 87 Participants | 29 Participants | 116 Participants |
| SARS-CoV-2 status at baseline Positive | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 44 Participants | 17 Participants | 61 Participants |
| Sex: Female, Male Male | 43 Participants | 12 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 87 | 0 / 29 |
| other Total, other adverse events | 45 / 87 | 17 / 29 |
| serious Total, serious adverse events | 5 / 87 | 2 / 29 |
Outcome results
Primary
The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs.
The safety profile will be evaluated using vital signs, laboratory data, electrocardiograms (ECGs), and adverse event data
Time frame: up to Day 181
Population: Safety analysis population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| AZD3152 | The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | Adverse Events | 45 Participants |
| AZD3152 | The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | Serious Adverse Events | 5 Participants |
| AZD3152 | The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | Medically Attended Adverse Events | 14 Participants |
| AZD3152 | The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | Adverse Events of Special Interest | 0 Participants |
| Placebo | The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | Adverse Events of Special Interest | 0 Participants |
| Placebo | The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | Adverse Events | 17 Participants |
| Placebo | The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | Medically Attended Adverse Events | 7 Participants |
| Placebo | The Number and Proportion of Subjects With AEs, SAEs, MAAEs, AESIs. | Serious Adverse Events | 2 Participants |
Secondary
Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s)
GMFR (from baseline) of nAb titers against SARS-CoV-2 emerging dominant variant(s) circulating during the course of the study (measured in RU local laboratory)
Time frame: up to Day 181
Population: SARS-CoV-2 nAb Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD3152 | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 4. Day 29 GMFRs | 4.71 fold rise | Standard Deviation 2.295 |
| AZD3152 | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 5. Day 91 GMFRs | 2.81 fold rise | Standard Deviation 2.653 |
| AZD3152 | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 3. Day 15 GMFRs | 5.84 fold rise | Standard Deviation 2.491 |
| AZD3152 | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 6. Day 181 GMFRs | 1.71 fold rise | Standard Deviation 2.565 |
| AZD3152 | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 2. Day 8 GMFRs | 5.63 fold rise | Standard Deviation 2.663 |
| Placebo | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 6. Day 181 GMFRs | 1.55 fold rise | Standard Deviation 2.462 |
| Placebo | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 2. Day 8 GMFRs | 1.16 fold rise | Standard Deviation 1.941 |
| Placebo | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 3. Day 15 GMFRs | 1.24 fold rise | Standard Deviation 2.247 |
| Placebo | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 5. Day 91 GMFRs | 1.10 fold rise | Standard Deviation 1.986 |
| Placebo | Geometric Mean Fold Rise (GMFRs) of nAb Titers Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 4. Day 29 GMFRs | 1.33 fold rise | Standard Deviation 2.014 |
Secondary
Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s)
GMT of nAbs against SARS-CoV-2 emerging dominant variant(s) circulating during the course of the study (measured in RU local laboratory)
Time frame: up to Day 181
Population: SARS-CoV-2 nAb Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| AZD3152 | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Baseline GMT | 12.0 Titer | Standard Deviation 3.22 |
| AZD3152 | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 2. Day 8 GMT | 67.7 Titer | Standard Deviation 2.02 |
| AZD3152 | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 3. Day 15 GMT | 70.9 Titer | Standard Deviation 1.96 |
| AZD3152 | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 4. Day 29 GMT | 64.3 Titer | Standard Deviation 2.05 |
| AZD3152 | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 5. Day 91 GMT | 37.6 Titer | Standard Deviation 2.24 |
| AZD3152 | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 6. Day 181 GMT | 22.4 Titer | Standard Deviation 2.71 |
| Placebo | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 5. Day 91 GMT | 9.1 Titer | Standard Deviation 2.25 |
| Placebo | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Baseline GMT | 9.8 Titer | Standard Deviation 2.5 |
| Placebo | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 4. Day 29 GMT | 12.6 Titer | Standard Deviation 2.67 |
| Placebo | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 2. Day 8 GMT | 11.3 Titer | Standard Deviation 2.76 |
| Placebo | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 6. Day 181 GMT | 13.4 Titer | Standard Deviation 2.76 |
| Placebo | Geometric Mean Titer (GMT) of nAbs Against SARS-CoV-2 Emerging Dominant Variant(s) | Visit 3. Day 15 GMT | 12.1 Titer | Standard Deviation 2.89 |
Secondary
Incidence of a Post-treatment Symptomatic COVID-19 Case
Incidence of a post-treatment symptomatic COVID-19 case (negative RT-PCR at baseline to positive RT-PCR or positive antigen test at any time up to 6 months AND symptoms specified in the modified WHO definition of symptomatic COVID-19).
Time frame: up to Day 181
Population: Full analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AZD3152 | Incidence of a Post-treatment Symptomatic COVID-19 Case | 4 Participants |
| Placebo | Incidence of a Post-treatment Symptomatic COVID-19 Case | 2 Participants |