Respiratory Syncytial Virus Infections
Conditions
Keywords
Respiratory Syncytial Virus, RSV, Preterm 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 preterm infants who are between 29 and 35 weeks gestational age (GA) and entering their first Respiratory Syncytial Virus (RSV) season.
Detailed description
This pivotal Phase 2b study will determine if MEDI8897 will be efficacious in reducing medically attended RSV-confirmed lower respiratory tract infections (LRTI) in healthy preterm infants entering their first RSV season. The population to be enrolled is healthy preterm infants born between 29 weeks 0 days and 34 weeks 6 days GA who would not receive RSV prophylaxis. A total of 1500 infants will be randomized 2:1 to receive either MEDI8897 or placebo. Participants will be followed for 360 days after dosing. Enrollment is planned at approximately 197 sites across the USA, Canada, Europe, and the Southern Hemisphere.
Interventions
DRUGMEDI8897
A single IM dose of 50 mg on Day 1 of the study.
DRUGPlacebo
A single IM dose of placebo matched to MEDI8897 on Day 1 of the study.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 365 Days
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: 1. Healthy infants born between 29 weeks 0 days and 34 weeks 6 days GA. 2. Infants who are entering their first full RSV season at the time of screening. Key
Exclusion criteria
1. Meets American Academy of Pediatrics (AAP) or other local criteria to receive commercial palivizumab. 2. Any fever (\>= 100.4°F \[\>= 38.0°C\], regardless of route) or lower respiratory illness within 7 days prior to randomization. 3. Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of randomization. 4. Active RSV infection (a child with signs/symptoms of respiratory infection must have negative RSV testing) or known prior history of RSV infection. 5. 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 Medically Attended Respiratory Syncytial Virus (RSV) Confirmed Lower Respiratory Tract Infection (LRTI) | From Day 1 through Day 151 | The determination of medically attended RSV LRTI is based on objective clinical LRTI criteria and RSV test results obtained from analyzing the respiratory secretions using a validated RSV real time reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of RSV A or RSV B subtypes. Criteria for LRTI included documented physical exam findings of rhonchi, rales, crackles, or wheeze and any of the following: increased respiratory rate at rest (for age less than (\<) 2 months: greater than or equal to (\>=) 60 breaths/min; 2-6 months: \>= 50 breaths/min; and for \> 6 months - 2 years, \>= 40 breaths/min), or hypoxemia (in room air - oxygen saturation \< 95% at altitudes less than or equal to (\<=) 1800 meters or \< 92% at altitudes \> 1800 meters), or clinical signs of severe respiratory disease or dehydration secondary to inadequate oral intake due to respiratory distress (need for intravenous fluid). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | From Day 1 through Day 361 | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. |
| Number of Participants With Adverse Events of Special Interest (AESIs) and New Onset Chronic Diseases (NOCDs) | From Day 1 through Day 361 | An AESI was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. An AESI may be serious or non-serious. A NOCD is a newly diagnosed medical condition that is of a chronic, ongoing nature. It is observed after receiving study drug and is assessed by investigator as medically significant. |
| Number of Participants Hopitalized Due to Respiratory Syncytial Virus (RSV) Confirmed Lower Respiartory Tract Infection (LRTI) | From Day 1 through Day 151 | A RSV hospitalization is defined as either 1) a respiratory hospitalization with a positive RSV test within 2 days of hospitalization (primary) or 2) new onset of respiratory symptoms in an already hospitalized child, with an objective measure of worsening respiratory status and positive RSV test (nosocomial). |
| Elimination Half-life (t1/2) of MEDI8897 | Day 91 through Day 361 | Terminal elimination half-life (t½) is the time required for half of the drug to be eliminated from the serum. |
| Number of Participants With Positive Anti-drug Antibodies to MEDI8897 | Days 91, 151, and 361 | The number of participants with positive serum antibodies to MEDI8897 are reported. |
| Serum Concentration of MEDI8897 | Days 91, 151, and 361 | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Czechia, Estonia, Finland, France, Hungary, Italy, Latvia, Lithuania, New Zealand, Poland, South Africa, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted from 03-Nov-2016 to 06-Dec-2018.
Pre-assignment details
A total of 1540 participants were screened, out of which 1453 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a single intramuscular (IM) dose of placebo matched to MEDI8897 on Day 1 of the study. | 484 |
| MEDI8897 50 mg Participants received a single IM dose of MEDI8897 50 milligrams (mg) on Day 1 of the study. | 969 |
| Total | 1,453 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 11 | 26 |
| Overall Study | Other | 4 | 7 |
| Overall Study | Withdrawal by Subject | 11 | 21 |
Baseline characteristics
| Characteristic | MEDI8897 50 mg | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 3.29 Months STANDARD_DEVIATION 2.22 | 3.29 Months STANDARD_DEVIATION 2.25 | 3.28 Months STANDARD_DEVIATION 2.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 225 Participants | 316 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 743 Participants | 1136 Participants | 393 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 15 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 189 Participants | 256 Participants | 67 Participants |
| Race (NIH/OMB) More than one race | 12 Participants | 17 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 8 Participants | 11 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 62 Participants | 105 Participants | 43 Participants |
| Race (NIH/OMB) White | 693 Participants | 1048 Participants | 355 Participants |
| Sex: Female, Male Female | 468 Participants | 692 Participants | 224 Participants |
| Sex: Female, Male Male | 501 Participants | 761 Participants | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 479 | 2 / 968 |
| other Total, other adverse events | 402 / 479 | 804 / 968 |
| serious Total, serious adverse events | 81 / 479 | 108 / 968 |
Outcome results
Primary
Number of Participants With Medically Attended Respiratory Syncytial Virus (RSV) Confirmed Lower Respiratory Tract Infection (LRTI)
The determination of medically attended RSV LRTI is based on objective clinical LRTI criteria and RSV test results obtained from analyzing the respiratory secretions using a validated RSV real time reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of RSV A or RSV B subtypes. Criteria for LRTI included documented physical exam findings of rhonchi, rales, crackles, or wheeze and any of the following: increased respiratory rate at rest (for age less than (\<) 2 months: greater than or equal to (\>=) 60 breaths/min; 2-6 months: \>= 50 breaths/min; and for \> 6 months - 2 years, \>= 40 breaths/min), or hypoxemia (in room air - oxygen saturation \< 95% at altitudes less than or equal to (\<=) 1800 meters or \< 92% at altitudes \> 1800 meters), or clinical signs of severe respiratory disease or dehydration secondary to inadequate oral intake due to respiratory distress (need for intravenous fluid).
Time frame: From Day 1 through Day 151
Population: The ITT population included all participants who were randomized in the study and analyzed according to their randomized treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Medically Attended Respiratory Syncytial Virus (RSV) Confirmed Lower Respiratory Tract Infection (LRTI) | 46 Participants |
| MEDI8897 50 mg | Number of Participants With Medically Attended Respiratory Syncytial Virus (RSV) Confirmed Lower Respiratory Tract Infection (LRTI) | 25 Participants |
p-value: <0.000195% CI: [52.3, 81.2]Poisson regression
Secondary
Elimination Half-life (t1/2) of MEDI8897
Terminal elimination half-life (t½) is the time required for half of the drug to be eliminated from the serum.
Time frame: Day 91 through Day 361
Population: As-treated population included all randomized participants who received any study drug and analyzed according to the study drug they actually received. Participants with sufficient additional pharmacokinetics (PK) samples from unscheduled visits were analysed for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Elimination Half-life (t1/2) of MEDI8897 | 59.3 Days | Standard Deviation 9.6 |
Secondary
Number of Participants Hopitalized Due to Respiratory Syncytial Virus (RSV) Confirmed Lower Respiartory Tract Infection (LRTI)
A RSV hospitalization is defined as either 1) a respiratory hospitalization with a positive RSV test within 2 days of hospitalization (primary) or 2) new onset of respiratory symptoms in an already hospitalized child, with an objective measure of worsening respiratory status and positive RSV test (nosocomial).
Time frame: From Day 1 through Day 151
Population: The ITT population included all participants who were randomized in the study and analyzed according to their randomized treatment group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Hopitalized Due to Respiratory Syncytial Virus (RSV) Confirmed Lower Respiartory Tract Infection (LRTI) | 20 Participants |
| MEDI8897 50 mg | Number of Participants Hopitalized Due to Respiratory Syncytial Virus (RSV) Confirmed Lower Respiartory Tract Infection (LRTI) | 8 Participants |
p-value: 0.000295% CI: [51.9, 90.3]Poisson regression
Secondary
Number of Participants With Adverse Events of Special Interest (AESIs) and New Onset Chronic Diseases (NOCDs)
An AESI was one of scientific and medical interest specific to understanding of study drug and may have required close monitoring and rapid communication by investigator to the sponsor. An AESI may be serious or non-serious. A NOCD is a newly diagnosed medical condition that is of a chronic, ongoing nature. It is observed after receiving study drug and is assessed by investigator as medically significant.
Time frame: From Day 1 through Day 361
Population: As-treated population included all randomized participants who received any study drug and analyzed according to the study drug they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events of Special Interest (AESIs) and New Onset Chronic Diseases (NOCDs) | AESIs | 3 Participants |
| Placebo | Number of Participants With Adverse Events of Special Interest (AESIs) and New Onset Chronic Diseases (NOCDs) | NOCDs | 4 Participants |
| MEDI8897 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs) and New Onset Chronic Diseases (NOCDs) | AESIs | 5 Participants |
| MEDI8897 50 mg | Number of Participants With Adverse Events of Special Interest (AESIs) and New Onset Chronic Diseases (NOCDs) | NOCDs | 4 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies to MEDI8897
The number of participants with positive serum antibodies to MEDI8897 are reported.
Time frame: Days 91, 151, and 361
Population: As-treated population included all randomized participants who received any study drug and analyzed according to the study drug they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI8897 | Day 91 | 4 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI8897 | Day 151 | 6 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies to MEDI8897 | Day 361 | 8 Participants |
| MEDI8897 50 mg | Number of Participants With Positive Anti-drug Antibodies to MEDI8897 | Day 91 | 11 Participants |
| MEDI8897 50 mg | Number of Participants With Positive Anti-drug Antibodies to MEDI8897 | Day 151 | 17 Participants |
| MEDI8897 50 mg | Number of Participants With Positive Anti-drug Antibodies to MEDI8897 | Day 361 | 30 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.
Time frame: From Day 1 through Day 361
Population: As-treated population included all randomized participants who received any study drug and analyzed according to the study drug they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 416 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 81 Participants |
| MEDI8897 50 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TEAEs | 834 Participants |
| MEDI8897 50 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | TESAEs | 108 Participants |
Secondary
Serum Concentration of MEDI8897
Time frame: Days 91, 151, and 361
Population: As-treated population included all randomized participants who received any study drug and analyzed according to the study drug they actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Serum Concentration of MEDI8897 | Day 91 | 35.9 mcg/mL | Standard Deviation 10.9 |
| Placebo | Serum Concentration of MEDI8897 | Day 151 | 18.9 mcg/mL | Standard Deviation 7.4 |
| Placebo | Serum Concentration of MEDI8897 | Day 361 | 2.1 mcg/mL | Standard Deviation 1.1 |