Influenza A
Conditions
Keywords
Flu
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of VIR-2482 compared to placebo in preventing influenza A illness in healthy adults 18 to \<65 years of age without pre-existing risk factors for serious complications from influenza infection.
Interventions
BIOLOGICALVIR-2482 (450 mg)
VIR-2482 450mg given by intramuscular injection
BIOLOGICALVIR-2482 (1200 mg)
VIR-2482 1200 mg given by intramuscular injection
BIOLOGICALPlacebo
Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection
Sponsors
Vir Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to \< 65 years of age, at time of randomization * Participants must be in good health, determined from medical history and no clinically significant findings from physical examination, 12-lead electrocardiogram (ECG), vital signs, and laboratory values
Exclusion criteria
* History or clinical evidence of conditions considered high risk for developing influenza-related complications * History of confirmed influenza infection within 3 months prior to randomization. * Febrile illness with or without respiratory symptoms * History of malignancy within 5 years or participant is under evaluation for malignancy. * Any condition or receipt of any medication contraindicating IM injection, as judged by the investigator. * History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis * Participant has a clinically significant medical condition, physical exam finding, or abnormal laboratory result. * Prior or planned receipt of any influenza vaccine for the upcoming season. * Received any investigational agent within 90 days or within 5 half-lives of the investigational agent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Solicited Systemic Reactions | Up to Day 7 following study intervention administration | Systemic reactions from the study intervention diary card |
| Number of Participants With Clinical Laboratory Abnormalities | Up to 26 Weeks | Defined as graded abnormality in chemistry, hematology, liver function, or urinalysis clinical laboratory values as per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Trials at any time on/after receipt of study intervention. |
| Number of Participants With Solicited Injection Site Reactions | Up to Day 7 following study intervention administration | Injection site reactions from the study intervention diary card |
| Percentage of Participants With Protocol-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | Up to 24 Weeks | Protocol-defined ILI with confirmed influenza A defined as RT-PCR confirmed influenza A with at least one respiratory symptom and at least one systemic symptom |
| Number of Participants With Adverse Events (AEs) | Up to 26 Weeks | — |
| Number of Participants With Serious Adverse Events (SAEs) | Up to 26 Weeks | — |
| Number of Participants With Adverse Events of Special Interest (AESI) | Up to 26 Weeks | AESI is anaphylaxis per MedDRA anaphylaxis algorithmic SMQ |
| Number of Participants With Vital Sign Abnormalities | Up to 26 Weeks | Defined as a graded abnormality in systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, or oral temperature as per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials at any time on/after receipt of study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With WHO-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | Up to 24 Weeks | WHO-defined ILI with RT-PCR confirmed influenza A |
| Percentage of Participants With CDC-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | Up to 24 Weeks | CDC-defined ILI with RT-PCR confirmed influenza A |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| VIR-2482 (450 mg) VIR-2482 (450 mg): VIR-2482 450mg given by intramuscular injection | 981 |
| VIR-2482 (1200 mg) VIR-2482 (1200 mg): VIR-2482 1200 mg given by intramuscular injection | 992 |
| Placebo Placebo: Sterile 0.9% (w/v) sodium chloride solution given by intramuscular injection | 983 |
| Total | 2,956 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 2 | 3 | 0 |
| Overall Study | Incarcerated | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 25 | 19 | 17 |
| Overall Study | Participant randomized in error | 4 | 2 | 2 |
| Overall Study | Physician Decision | 10 | 7 | 9 |
| Overall Study | Study Terminated by Sponsor | 924 | 937 | 941 |
| Overall Study | Withdrawal by Subject | 23 | 27 | 24 |
Baseline characteristics
| Characteristic | VIR-2482 (450 mg) | VIR-2482 (1200 mg) | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 39.2 Years STANDARD_DEVIATION 12.52 | 39.6 Years STANDARD_DEVIATION 11.73 | 39.7 Years STANDARD_DEVIATION 12.29 | 39.5 Years STANDARD_DEVIATION 12.18 |
| Body Mass Index | 27.34 kg/m^2 STANDARD_DEVIATION 4.085 | 27.44 kg/m^2 STANDARD_DEVIATION 4.167 | 27.4 kg/m^2 STANDARD_DEVIATION 4.071 | 27.34 kg/m^2 STANDARD_DEVIATION 4.107 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 371 Participants | 369 Participants | 357 Participants | 1097 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 606 Participants | 622 Participants | 620 Participants | 1848 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 7 Participants | 7 Participants | 7 Participants | 21 Participants |
| Race (NIH/OMB) Asian | 26 Participants | 29 Participants | 26 Participants | 81 Participants |
| Race (NIH/OMB) Black or African American | 154 Participants | 176 Participants | 166 Participants | 496 Participants |
| Race (NIH/OMB) More than one race | 17 Participants | 11 Participants | 6 Participants | 34 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 4 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants | 18 Participants | 16 Participants | 54 Participants |
| Race (NIH/OMB) White | 752 Participants | 747 Participants | 758 Participants | 2257 Participants |
| Region of Enrollment United States | 981 participants | 992 participants | 983 participants | 2956 participants |
| Sex: Female, Male Female | 545 Participants | 523 Participants | 530 Participants | 1598 Participants |
| Sex: Female, Male Male | 436 Participants | 469 Participants | 453 Participants | 1358 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 981 | 3 / 992 | 0 / 983 |
| other Total, other adverse events | 454 / 981 | 450 / 992 | 460 / 983 |
| serious Total, serious adverse events | 10 / 981 | 13 / 992 | 9 / 983 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
Time frame: Up to 26 Weeks
Population: Participants who received any amount of study intervention. Participants were analyzed according to study intervention received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIR-2482 (450 mg) | Number of Participants With Adverse Events (AEs) | 636 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Adverse Events (AEs) | 613 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | 639 Participants |
Primary
Number of Participants With Adverse Events of Special Interest (AESI)
AESI is anaphylaxis per MedDRA anaphylaxis algorithmic SMQ
Time frame: Up to 26 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIR-2482 (450 mg) | Number of Participants With Adverse Events of Special Interest (AESI) | 0 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Adverse Events of Special Interest (AESI) | 0 Participants |
| Placebo | Number of Participants With Adverse Events of Special Interest (AESI) | 0 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities
Defined as graded abnormality in chemistry, hematology, liver function, or urinalysis clinical laboratory values as per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Trials at any time on/after receipt of study intervention.
Time frame: Up to 26 Weeks
Population: Participants who received any amount of study intervention and had a post-baseline clinical laboratory assessment. Participants were analyzed according to the study intervention received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIR-2482 (450 mg) | Number of Participants With Clinical Laboratory Abnormalities | 961 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Clinical Laboratory Abnormalities | 971 Participants |
| Placebo | Number of Participants With Clinical Laboratory Abnormalities | 961 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs)
Time frame: Up to 26 Weeks
Population: Participants who received any amount of study intervention. Participants were analyzed according to the study intervention received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIR-2482 (450 mg) | Number of Participants With Serious Adverse Events (SAEs) | 10 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Serious Adverse Events (SAEs) | 13 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) | 9 Participants |
Primary
Number of Participants With Solicited Injection Site Reactions
Injection site reactions from the study intervention diary card
Time frame: Up to Day 7 following study intervention administration
Population: Participants who received any amount of study intervention . Participants were analyzed according to the study intervention received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIR-2482 (450 mg) | Number of Participants With Solicited Injection Site Reactions | Any injection site reaction | 292 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Injection Site Reactions | Pain | 279 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Injection Site Reactions | Erythema | 7 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Injection Site Reactions | Induration | 8 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Injection Site Reactions | Swelling | 10 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Injection Site Reactions | Bruising | 17 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Injection Site Reactions | Bruising | 20 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Injection Site Reactions | Any injection site reaction | 293 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Injection Site Reactions | Induration | 12 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Injection Site Reactions | Swelling | 13 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Injection Site Reactions | Pain | 277 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Injection Site Reactions | Erythema | 10 Participants |
| Placebo | Number of Participants With Solicited Injection Site Reactions | Pain | 260 Participants |
| Placebo | Number of Participants With Solicited Injection Site Reactions | Erythema | 5 Participants |
| Placebo | Number of Participants With Solicited Injection Site Reactions | Bruising | 21 Participants |
| Placebo | Number of Participants With Solicited Injection Site Reactions | Induration | 3 Participants |
| Placebo | Number of Participants With Solicited Injection Site Reactions | Any injection site reaction | 272 Participants |
| Placebo | Number of Participants With Solicited Injection Site Reactions | Swelling | 2 Participants |
Primary
Number of Participants With Solicited Systemic Reactions
Systemic reactions from the study intervention diary card
Time frame: Up to Day 7 following study intervention administration
Population: Participants who received any amount of study intervention . Participants were analyzed according to the study intervention received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VIR-2482 (450 mg) | Number of Participants With Solicited Systemic Reactions | Headache | 160 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Systemic Reactions | Myalgia | 135 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Systemic Reactions | Fever | 11 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Systemic Reactions | Any systemic reaction | 265 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Systemic Reactions | Malaise | 117 Participants |
| VIR-2482 (450 mg) | Number of Participants With Solicited Systemic Reactions | Shivering | 44 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Systemic Reactions | Malaise | 130 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Systemic Reactions | Shivering | 60 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Systemic Reactions | Fever | 11 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Systemic Reactions | Headache | 168 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Systemic Reactions | Any systemic reaction | 283 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Solicited Systemic Reactions | Myalgia | 169 Participants |
| Placebo | Number of Participants With Solicited Systemic Reactions | Fever | 13 Participants |
| Placebo | Number of Participants With Solicited Systemic Reactions | Any systemic reaction | 268 Participants |
| Placebo | Number of Participants With Solicited Systemic Reactions | Headache | 175 Participants |
| Placebo | Number of Participants With Solicited Systemic Reactions | Myalgia | 149 Participants |
| Placebo | Number of Participants With Solicited Systemic Reactions | Shivering | 43 Participants |
| Placebo | Number of Participants With Solicited Systemic Reactions | Malaise | 123 Participants |
Primary
Number of Participants With Vital Sign Abnormalities
Defined as a graded abnormality in systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, or oral temperature as per the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials at any time on/after receipt of study intervention.
Time frame: Up to 26 Weeks
Population: Participants who received any amount of study intervention and had a post-baseline vital sign measurement. Participants were analyzed according to the study intervention received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VIR-2482 (450 mg) | Number of Participants With Vital Sign Abnormalities | 678 Participants |
| VIR-2482 (1200 mg) | Number of Participants With Vital Sign Abnormalities | 662 Participants |
| Placebo | Number of Participants With Vital Sign Abnormalities | 648 Participants |
Primary
Percentage of Participants With Protocol-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR])
Protocol-defined ILI with confirmed influenza A defined as RT-PCR confirmed influenza A with at least one respiratory symptom and at least one systemic symptom
Time frame: Up to 24 Weeks
Population: Full Analysis Set (all randomized who did not have confirmed influenza infection within 3 months prior to randomization, did not receive an influenza vaccination for the upcoming influenza season, and received any amount of study intervention). Participants were analyzed according to the randomized study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIR-2482 (450 mg) | Percentage of Participants With Protocol-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 2.45 percentage of participants |
| VIR-2482 (1200 mg) | Percentage of Participants With Protocol-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 2.12 percentage of participants |
| Placebo | Percentage of Participants With Protocol-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 2.54 percentage of participants |
p-value: 0.555295% CI: [-49.27, 52.56]Poisson regression
95% CI: [-67.23, 44.63]
Secondary
Percentage of Participants With CDC-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR])
CDC-defined ILI with RT-PCR confirmed influenza A
Time frame: Up to 24 Weeks
Population: Full Analysis Set (all randomized who did not have confirmed influenza infection within 3 months prior to randomization, did not receive an influenza vaccination for the upcoming influenza season, and received any amount of study intervention). Participants were analyzed according to the randomized study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIR-2482 (450 mg) | Percentage of Participants With CDC-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 1.53 percentage of participants |
| VIR-2482 (1200 mg) | Percentage of Participants With CDC-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 0.71 percentage of participants |
| Placebo | Percentage of Participants With CDC-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 1.73 percentage of participants |
95% CI: [-2.51, 82.15]
95% CI: [-76.25, 55.51]
Secondary
Percentage of Participants With WHO-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR])
WHO-defined ILI with RT-PCR confirmed influenza A
Time frame: Up to 24 Weeks
Population: Full Analysis Set (all randomized who did not have confirmed influenza infection within 3 months prior to randomization, did not receive an influenza vaccination for the upcoming influenza season, and received any amount of study intervention). Participants were analyzed according to the randomized study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VIR-2482 (450 mg) | Percentage of Participants With WHO-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 1.22 percentage of participants |
| VIR-2482 (1200 mg) | Percentage of Participants With WHO-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 0.6 percentage of participants |
| Placebo | Percentage of Participants With WHO-defined Influenza-like Illness (ILI) With Confirmed Influenza A (by Reverse Transcription Polymerase Chain Reaction [RT-PCR]) | 1.12 percentage of participants |
95% CI: [-50.49, 79.26]
95% CI: [-147.41, 51.27]