Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory Syncytial Virus, RSV, Late Preterm Infants, Healthy Infants, Lower Respiratory Tract Infection
Brief summary
The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), and antidrug antibody (ADA) response for MEDI8897 in healthy late preterm and term infants who are 35 weeks or greater gestational age and entering their first RSV season.
Detailed description
This pivotal Phase 3 study will determine if MEDI8897 will prevent medically attended RSV-confirmed lower respiratory tract infections (LRTI) in healthy infants entering their first RSV season. The population to be enrolled is healthy late preterm and term infants born 35 weeks 0 days or greater gestational age (GA) who would not be eligible to receive RSV prophylaxis. A total of approximately 3,000 infants will be randomized 2:1 to receive either MEDI8897 or placebo. All subjects will be followed for approximately 510 days after dosing. Enrollment is planned at approximately 350 sites across the USA, Canada, Europe, Asia, and Southern Hemisphere.
Interventions
DRUGMEDI8897
Anti-RSV monoclonal antibody with an extended half-life
DRUGPlacebo
Commercially available 0.9% (w/v) saline
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
0 Years to 1 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Healthy infants in their first year of life and born at or after 35 weeks 0 days GA * Infants who are entering their first RSV season at the time of screening Key
Exclusion criteria
* Meets national or other local criteria to receive commercial palivizumab * Any fever (≥ 100.4°F \[≥ 38.0°C\], regardless of route) or acute illness within 7 days prior to randomization * Active RSV infection (a child with signs/symptoms of respiratory infection must have negative RSV testing) or known prior history of RSV infection * Receipt of palivizumab or other RSV monoclonal antibody or any RSV vaccine, including maternal RSV vaccination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With MA RSV LRTI Through 150 Days Post Dose (Primary Cohort) | Through 150 Days Post Dose | Primary Endpoint Analysed on Primary Cohort Through 150 Days (N=1490 Participants) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (Primary Cohort) | Through 150 Days Post Dose | Hospitalization Analysed on Primary Cohort Through 150 Days (N=1490 Participants) |
| Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | By visit until day 360 post dose | Number of Subjects with at Least one Assessment |
| Anti-drug Antibody Results by Visit (As Treated Population) | From baseline to 360 day post dose visit | Number of subjects with a positive result and a valid titer result at the specific visit |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (All Subjects) | Through 150 Days Post Dose | Hospitalization Analysed on All Subjects Through 150 Days (N=3012 participants) |
| Number of Participants With Disease From the 2nd RSV Season (All Subjects) | From Day 361 to Day 510 Post Dose | — |
| Number of Participants With MA RSV LRTI Through 150 Days Post Dose (All Subjects) | Through 150 Days Post Dose | Primary Endpoint Analysed on All Subjects Through 150 Days (N=3012 participants) |
Countries
Argentina, Australia, Austria, Belgium, Bulgaria, Canada, Chile, Colombia, Czechia, Estonia, Finland, France, Germany, Israel, Italy, Japan, Latvia, Lithuania, Mexico, New Zealand, Panama, Poland, Russia, South Africa, South Korea, Spain, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
First Subject In: 23-07-2019. Last Subject Last Visit: 21-03-2023. The study was planned to analyze data on the full enrolment of approximately 3000 infants. The impact of the COVID-19 pandemic on RSV circulation led to the decision to analyze the primary endpoint based on the first 1500 subjects enrolled (Primary Cohort). After the COVID-19 pandemic the study restarted. So the study comprised 2 cohorts: a Primary and a Safety for a total of 3319 screened subjects.
Pre-assignment details
1626 screened subjects in Primary Cohort. 136 subjects did not start the study: 98 not meeting the I/E criteria, 6 lost to follow-up, 25 withdrew the informed consent, 7 for other reason. Overall 3319 screened subjects. 307 did not start the study: 192 not meeting the I/E criteria, 11 lost to follow-up, 90 withdrew the informed consent, 14 for other reason.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Single IM dose of 50 mg (if \< 5 kg weight at time of dosing) or 100 mg (if ≥ 5 kg weight at time of dosing). | 1,003 |
| Medi8897 Single IM dose of 50 mg (if \< 5 kg weight at time of dosing) or 100 mg (if ≥ 5 kg weight at time of dosing). | 2,009 |
| Total | 3,012 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| All Subjects | Any Other Reason | 16 | 23 |
| All Subjects | Covid-19 | 1 | 3 |
| All Subjects | Death | 0 | 5 |
| All Subjects | Lost to Follow-up | 28 | 61 |
| All Subjects | Withdrawal by Subject | 35 | 44 |
| Primary Cohort (Data Cut Off 11/3/2021) | Any Other Reason | 3 | 4 |
| Primary Cohort (Data Cut Off 11/3/2021) | Covid-19 pandemic | 1 | 3 |
| Primary Cohort (Data Cut Off 11/3/2021) | Death | 0 | 4 |
| Primary Cohort (Data Cut Off 11/3/2021) | Lost to Follow-up | 3 | 9 |
| Primary Cohort (Data Cut Off 11/3/2021) | Ongoing at the DCO date | 432 | 865 |
| Primary Cohort (Data Cut Off 11/3/2021) | Withdrawal by Subject | 14 | 20 |
Baseline characteristics
| Characteristic | Placebo | Medi8897 | Total |
|---|---|---|---|
| Age, Continuous Age (months) in All Subjects | 2.918 Months STANDARD_DEVIATION 2.274 | 2.905 Months STANDARD_DEVIATION 2.22 | 2.909 Months STANDARD_DEVIATION 2.2376 |
| Age, Continuous Age (months) in Primary Cohort | 3.012 Months STANDARD_DEVIATION 2.252 | 2.912 Months STANDARD_DEVIATION 2.2099 | 2.946 Months STANDARD_DEVIATION 2.2237 |
| Race/Ethnicity, Customized Race in All Subjects American Indian or Alaska Native | 52 Participants | 92 Participants | 144 Participants |
| Race/Ethnicity, Customized Race in All Subjects Asian | 50 Participants | 109 Participants | 159 Participants |
| Race/Ethnicity, Customized Race in All Subjects Black or African American | 138 Participants | 299 Participants | 437 Participants |
| Race/Ethnicity, Customized Race in All Subjects Missing | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race in All Subjects Multiple categories checked | 8 Participants | 19 Participants | 27 Participants |
| Race/Ethnicity, Customized Race in All Subjects Native Hawaiian or other Pacific Islander | 8 Participants | 15 Participants | 23 Participants |
| Race/Ethnicity, Customized Race in All Subjects Other | 206 Participants | 420 Participants | 626 Participants |
| Race/Ethnicity, Customized Race in All Subjects White | 541 Participants | 1052 Participants | 1593 Participants |
| Race/Ethnicity, Customized Race in Primary Cohort American Indian or Alaska Native | 26 Participants | 57 Participants | 83 Participants |
| Race/Ethnicity, Customized Race in Primary Cohort Asian | 18 Participants | 36 Participants | 54 Participants |
| Race/Ethnicity, Customized Race in Primary Cohort Black or African American | 136 Participants | 286 Participants | 422 Participants |
| Race/Ethnicity, Customized Race in Primary Cohort Missing | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race in Primary Cohort Multiple categories checked | 1 Participants | 12 Participants | 13 Participants |
| Race/Ethnicity, Customized Race in Primary Cohort Native Hawaiian or other Pacific Islander | 5 Participants | 6 Participants | 11 Participants |
| Race/Ethnicity, Customized Race in Primary Cohort Other | 38 Participants | 70 Participants | 108 Participants |
| Race/Ethnicity, Customized Race in Primary Cohort White | 272 Participants | 524 Participants | 796 Participants |
| Sex: Female, Male Sex in All Subjects Female | 500 Participants | 938 Participants | 1438 Participants |
| Sex: Female, Male Sex in All Subjects Male | 503 Participants | 1071 Participants | 1574 Participants |
| Sex: Female, Male Sex in Primary Cohort Female | 257 Participants | 464 Participants | 721 Participants |
| Sex: Female, Male Sex in Primary Cohort Male | 239 Participants | 530 Participants | 769 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 997 | 5 / 1,997 |
| other Total, other adverse events | 836 / 997 | 1,717 / 1,997 |
| serious Total, serious adverse events | 83 / 997 | 149 / 1,997 |
Outcome results
Primary
Number of Participants With MA RSV LRTI Through 150 Days Post Dose (Primary Cohort)
Primary Endpoint Analysed on Primary Cohort Through 150 Days (N=1490 Participants)
Time frame: Through 150 Days Post Dose
Population: ITT population / Primary Cohort
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (Primary Cohort) | Subjects without event through day 150 post dose | 465 Participants |
| Placebo | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (Primary Cohort) | Observed events through day 150 post dose | 25 Participants |
| Placebo | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (Primary Cohort) | Subjects requiring imputation (Subjects without events and not followed through 150 days post dose) | 6 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (Primary Cohort) | Observed events through day 150 post dose | 12 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (Primary Cohort) | Subjects requiring imputation (Subjects without events and not followed through 150 days post dose) | 15 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (Primary Cohort) | Subjects without event through day 150 post dose | 967 Participants |
p-value: <0.000195% CI: [49.63, 87.12]Poisson Model
Secondary
Anti-drug Antibody Results by Visit (As Treated Population)
Number of subjects with a positive result and a valid titer result at the specific visit
Time frame: From baseline to 360 day post dose visit
Population: As Treated Population / All Subjects
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Anti-drug Antibody Results by Visit (As Treated Population) | Baseline | 4 Participants |
| Placebo | Anti-drug Antibody Results by Visit (As Treated Population) | Day 30 Post Dose | 2 Participants |
| Placebo | Anti-drug Antibody Results by Visit (As Treated Population) | Day 150 Post Dose | 1 Participants |
| Placebo | Anti-drug Antibody Results by Visit (As Treated Population) | Day 360 Post Dose | 10 Participants |
| Medi8897 | Anti-drug Antibody Results by Visit (As Treated Population) | Day 360 Post Dose | 81 Participants |
| Medi8897 | Anti-drug Antibody Results by Visit (As Treated Population) | Baseline | 4 Participants |
| Medi8897 | Anti-drug Antibody Results by Visit (As Treated Population) | Day 150 Post Dose | 21 Participants |
| Medi8897 | Anti-drug Antibody Results by Visit (As Treated Population) | Day 30 Post Dose | 14 Participants |
Secondary
Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (Primary Cohort)
Hospitalization Analysed on Primary Cohort Through 150 Days (N=1490 Participants)
Time frame: Through 150 Days Post Dose
Population: ITT population / Primary Cohort
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (Primary Cohort) | Observed events through day 150 post dose | 8 Participants |
| Placebo | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (Primary Cohort) | Subjects requiring imputation (subjects without events and not followed through 150 days post dose) | 6 Participants |
| Placebo | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (Primary Cohort) | Subjects without event through day 150 post dose | 482 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (Primary Cohort) | Observed events through day 150 post dose | 6 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (Primary Cohort) | Subjects requiring imputation (subjects without events and not followed through 150 days post dose) | 15 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (Primary Cohort) | Subjects without event through day 150 post dose | 973 Participants |
p-value: 0.070895% CI: [-8.57, 86.8]Poisson Model
Secondary
Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group
Number of Subjects with at Least one Assessment
Time frame: By visit until day 360 post dose
Population: As Treated Population (1997 Participants Treated in MEDI8897 arm)/ All Subjects
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 14 Post Dose | 74.09 ug/mL | Geometric Coefficient of Variation 124.9 |
| Placebo | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 150 Post Dose | 18.32 ug/mL | Geometric Coefficient of Variation 63.1 |
| Placebo | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 30 Post Dose | 68.63 ug/mL | Geometric Coefficient of Variation 58.6 |
| Placebo | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 360 Post Dose | 1.75 ug/mL | Geometric Coefficient of Variation 76.7 |
| Placebo | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 7 Post Dose | 89.91 ug/mL | Geometric Coefficient of Variation 39.3 |
| Medi8897 | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 360 Post Dose | 2.86 ug/mL | Geometric Coefficient of Variation 85.7 |
| Medi8897 | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 7 Post Dose | 164.03 ug/mL | Geometric Coefficient of Variation 15.8 |
| Medi8897 | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 14 Post Dose | 105.05 ug/mL | Geometric Coefficient of Variation 89.2 |
| Medi8897 | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 30 Post Dose | 100.54 ug/mL | Geometric Coefficient of Variation 90.1 |
| Medi8897 | Summary of Serum Concentrations (ug/mL) of MEDI8897 by Group | Day 150 Post Dose | 27.73 ug/mL | Geometric Coefficient of Variation 62.9 |
Other Pre-specified
Number of Participants With Disease From the 2nd RSV Season (All Subjects)
Time frame: From Day 361 to Day 510 Post Dose
Population: ITT population / All Subjects
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Disease From the 2nd RSV Season (All Subjects) | MA RSV LRTI (protocol defined) | 10 Participants |
| Placebo | Number of Participants With Disease From the 2nd RSV Season (All Subjects) | MA RSV LRTI hospitalisation (protocol defined) | 3 Participants |
| Medi8897 | Number of Participants With Disease From the 2nd RSV Season (All Subjects) | MA RSV LRTI (protocol defined) | 19 Participants |
| Medi8897 | Number of Participants With Disease From the 2nd RSV Season (All Subjects) | MA RSV LRTI hospitalisation (protocol defined) | 3 Participants |
Other Pre-specified
Number of Participants With MA RSV LRTI Through 150 Days Post Dose (All Subjects)
Primary Endpoint Analysed on All Subjects Through 150 Days (N=3012 participants)
Time frame: Through 150 Days Post Dose
Population: ITT population / All Subjects
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (All Subjects) | Observed events through day 150 post dose | 54 Participants |
| Placebo | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (All Subjects) | Subjects requiring imputation (Subjects without events and not followed through 150 days post dose) | 17 Participants |
| Placebo | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (All Subjects) | Subjects without event through day 150 post dose | 932 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (All Subjects) | Observed events through day 150 post dose | 24 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (All Subjects) | Subjects requiring imputation (Subjects without events and not followed through 150 days post dose) | 31 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI Through 150 Days Post Dose (All Subjects) | Subjects without event through day 150 post dose | 1954 Participants |
p-value: <0.000195% CI: [62.27, 85.18]Poisson Model
Other Pre-specified
Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (All Subjects)
Hospitalization Analysed on All Subjects Through 150 Days (N=3012 participants)
Time frame: Through 150 Days Post Dose
Population: ITT population / All Subjects
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (All Subjects) | Observed events through day 150 post dose | 20 Participants |
| Placebo | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (All Subjects) | Subjects requiring imputation (Subjects without events and not followed through 150 days post dose) | 18 Participants |
| Placebo | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (All Subjects) | Subjects without event through day 150 post dose | 965 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (All Subjects) | Observed events through day 150 post dose | 9 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (All Subjects) | Subjects requiring imputation (Subjects without events and not followed through 150 days post dose) | 31 Participants |
| Medi8897 | Number of Participants With MA RSV LRTI With Hospitalisation Through 150 Days Post Dose (All Subjects) | Subjects without event through day 150 post dose | 1969 Participants |
p-value: 0.000295% CI: [49.36, 89.41]Poisson Model