A Study to Evaluate the Safety and Efficacy of MEDI8897 for the Prevention of Medically Attended RSV LRTI in Healthy Preterm Infants.

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2b Randomized, Double-Blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in Healthy Preterm Infants

Conditions
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Respiratory Syncytial Virus Infections

Intervention / Treatment
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* Drug: MEDI8897
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy infants born between 29 weeks 0 days and 34 weeks 6 days GA. Infants who are entering their first full RSV season at the time of screening. Key Exclusion Criteria: Meets American Academy of Pediatrics (AAP) or other local criteria to receive commercial palivizumab. Any fever (>= 100.4°F [>= 38.0°C], regardless of route) or lower respiratory illness within 7 days prior to randomization. Acute illness (defined as the presence of moderate or severe signs and symptoms) at the time of 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.

Ages Eligible for Study
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Maximum Age: 365 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants will receive a single intramuscular (IM) dose of placebo matched to MEDI8897 on Day 1 of the study. | Drug: Placebo<br>* A single IM dose of placebo matched to MEDI8897 on Day 1 of the study.<br>|
| Experimental: MEDI8897 50 mg<br>Participants will receive a single IM dose of MEDI8897 50 milligrams (mg) on Day 1 of the study. | Drug: MEDI8897<br>* A single IM dose of 50 mg on Day 1 of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | From Day 1 through Day 151 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | From Day 1 through Day 151 | 
| 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. | From Day 1 through Day 361 | 
| 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. | From Day 1 through Day 361 | 
| Serum Concentration of MEDI8897 |  | Days 91, 151, and 361 | 
| 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. | Day 91 through Day 361 | 
| Number of Participants With Positive Anti-drug Antibodies to MEDI8897 | The number of participants with positive serum antibodies to MEDI8897 are reported. | Days 91, 151, and 361 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Syncytial Virus, RSV, Preterm Infants, Lower Respiratory Tract Infection