MEDI-524 (Motavizumab) for the Prevention of Respiratory Sycytial Virus (RSV) Disease Among Native American Indian Infants in the Southwestern United States

Study Overview
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Brief Summary
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MI-CP117 was a Phase 3, randomized, double-blind, placebo-controlled trial designed to determine if motavizumab is more effective than placebo in reducing RSV hospitalization in otherwise healthy Native American Infants in the Southwestern United States during their first RSV season.

Detailed Description
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MI-CP117 was a Phase 3, randomized, double-blind, placebo-controlled trial designed to determine if motavizumab is more effective than placebo in reducing RSV hospitalization in otherwise healthy Native American infants during their first RSV season. Participants were randomized in a 2:1 ratio to receive either 15 mg/kg motavizumab or placebo by intramuscular (IM) injection every 30 days during the RSV season for a maximum of 5 injections. During their first RSV season, participants were evaluated monthly just prior to each injection of study drug for adverse events (AEs) (including medically attended otitis media), with a final post-dosing follow up evaluation at Study Day 150. During Seasons 1, 2, and 3, blood was to be collected prior to the first and last dose of study drug for serum chemistry evaluations, motavizumab serum concentrations, and anti-motavizumab antibodies. Efficacy and safety outcomes were examined through Study Day 150 and wheezing outcomes were evaluated from the time of randomization until the third birthday.

Official Title
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A Phase 3 Study of MEDI-524 (Motavizumab), an Enhanced Potency Humanized Respiratory Syncytial Virus (RSV) Monoclonal Antibody, for the Prevention of RSV Disease Among Native American Infants in the Southwestern United States

Conditions
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Healthy

Intervention / Treatment
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* Biological: Motavizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 6 months of age or younger at randomization (child must be randomized on or before their 6-month birthday) Male or female Native American General state of good health Written informed consent obtained from the participant's parent(s) or legal guardian Exclusion Criteria: Gestational age less than or equal to 35 weeks Chronic lung disease of prematurity A bleeding diathesis that would preclude IM injections Hospitalization at the time of randomization (unless discharge is anticipated within 10 days) Active RSV infection (a child with signs/symptoms of respiratory infection must have negative RSV testing) or known prior history of RSV infection A documented wheezing episode before enrollment Known renal impairment Known hepatic dysfunction Clinically significant congenital anomaly of the respiratory tract Chronic seizure or evolving or unstable neurologic disorder Congenital heart disease (CHD) (children with uncomplicated CHD [e.g., Patent ductus arteriosus, small septal defect] and children with complicated CHD who are currently anatomically and hemodynamically) Known immunodeficiency Mother with human immunodeficiency virus infection (unless the child has been proven to be not infected) Known allergy to Ig products Receipt of palivizumab, Respiratory syncytial virus immunoglobulin, intravenous (RSV-IGIV), or other RSV-specific monoclonal antibody, or any other polyclonal antibody (for example, hepatitis B immunoglobulin, IVIG) within 3 months prior to randomization Anticipated use of palivizumab or IVIG during the study (blood transfusions permitted) Previous receipt of RSV vaccines Participation in other investigational drug product studies Any medical or social condition which, in the opinion of the investigator, would adversely affect monitoring the infant Inability to complete the study follow-up period through up to 5 years of age

Ages Eligible for Study
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Minimum Age: 0 Months
Maximum Age: 6 Months

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 IM dose of placebo matched to motavizumab every 30 days for a maximum of 5 injections (on Days 0, 30, 60, 90, and 120) during the the RSV season. | Other: Placebo<br>* Intramuscular dose of placebo matched to motavizumab will be administered every 30 days for a maximum of 5 injections (on Days 0, 30, 60, 90, and 120) during the the RSV season.<br>|
| Active Comparator: Motavizumab<br>Participants will receive IM dose of motavizumab 15 milligram/Kilogram (mg/kg) every 30 Days for a maximum of 5 injections (on Days 0, 30, 60, 90, and 120) during the RSV season. | Biological: Motavizumab<br>* Intramuscular dose of motavizumab 15 mg/kg will be administered every 30 Days for a maximum of 5 injections (on Days 0, 30, 60, 90, and 120) during the RSV season.<br>* Other names: MEDI-524;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Respiratory Syncytial Virus (RSV) Hospitalization | An RSV hospitalization is defined as either 1) a respiratory hospitalization with a positive central real-time reverse transcription polymerase chain reaction (RT-PCR) RSV test collected within 3 days of hospitalization or 2) new onset of lower respiratory symptoms in an already hospitalized child, with an objective measure of worsening respiratory status and positive RSV test. | From study Day 0 through study Day 150 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. The 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 study Day 0 through study Day 150 | 
| Number of Participants With RSV Outpatient Medically Attended Lower Respiratory Illness (MA LRI) | The RSV outpatient MA LRI was defined as an outpatient medically attended event designated as a lower respiratory illness with a positive RT-PCR RSV test. An LRI event is one that has a medical diagnosis of bronchiolitis or pneumonia. In the absence of such a medical diagnosis, the occurrence of LRI events was determined by the principal investigator after review of the medical record and considering the presence of cough, retractions, rhonchi, wheezing, crackles, or rales, associated with symptoms (by history or clinical findings) of coryza, fever, or apnoea. | From study Day 0 through study Day 150 | 
| Number of Participants With Medically Attended-Otitis Media (MA-OM) Events | Otitis media (OM) was recorded as the diagnosis if the following terms were used by the medical care provider: acute OM, acute tympanic membrane (TM) perforation, bulging TM, red TM with fever, OM with effusion, or middle ear effusion. A new episode was defined as a physician-diagnosed OM in either ear after a normal middle ear exam of the ear in question or an episode of acute OM greater than or equal to 21 days after resolution of the previous episode. A diagnosis of persistent middle ear effusion was not recorded as a new OM event. | From study Day 0 through study Day 150 | 
| Number of Participants With Frequency of MA-OM Events | Otitis media was recorded as the diagnosis if the following terms were used by the medical care provider: acute OM, acute TM perforation, bulging TM, red TM with fever, OM with effusion, or middle ear effusion. A new episode was defined as a physician-diagnosed OM in either ear after a normal middle ear exam of the ear in question or an episode of acute OM greater than or equal to 21 days after resolution of the previous episode. A diagnosis of persistent middle ear effusion was not recorded as a new OM event. Number of participants with frequency of MA-OM events (either 0, 1, 2, 3, or greater than [>] 3) are reported. | From study Day 0 through study Day 150 | 
| Number of Participants With Medically Attended Wheezing Episodes | Wheezing events were included in the analysis of medically-attended wheezing, if the medical care provider documented wheezing in the medical record or records as a discharge diagnosis any of asthma, bronchiolitis, wheezing, or reactive airway disease. A new wheezing episode was recorded as one that occurred >2 weeks after the diagnosis of the previous episode and the medical opinion was that the wheezing does not represent a persistence of the previous episode. Number of participants with greater than or equal to (>=) 1 MA wheezing events and >= 3 MA wheezing events occurring from first through 3 years of age are reported. | From first year through 3 years | 
| Number of Participants With Serious Early Childhood Wheezing Episodes | Serious early childhood wheezing (SECW) was defined as: three or more medically attended wheezing events over a 12 month period occurring any time from the first through the third birthday, or a need for one or more courses of systemic steroids for a treatment of a medically attended wheezing event from the first through the third birthday, or a need for asthma-controller medication over a 12 month period for at least 3 consecutive months (>= 90 days) or 5 cumulative months (>= 150 days) any time from the first through the third birthday, or at least one inpatient wheezing event from the first through the third birthday. | From first year through 3 years | 
| Number of Participants With Frequency of Medically Attended Wheezing Events | Wheezing events were included in the analysis of medically-attended wheezing, if the medical care provider documented wheezing in the medical record or records as a discharge diagnosis any of asthma, bronchiolitis, wheezing, or reactive airway disease. A new wheezing episode was recorded as one that occurred >2 weeks after the diagnosis of the previous episode and the medical opinion is that the wheezing does not represent a persistence of the previous episode. Number of participants with frequency of MA wheezing events (either 0, 1, 2, 3, 4, or greater than or equal to [>=] 5) are reported. | Study Day 0 through 3 years | 
| Mean Trough Serum Concentrations of Motavizumab | The mean trough serum concentrations of motavizumab are reported. | Day 0 (pre Dose 1) and Day 120 (Pre Dose 5) | 
| Number of Participants With Positive Anti-Motavizumab Antibodies After Full Dose | The number of participants with positive serum antidrug antibodies (ADAs) to motavizumab after full dose are reported. | Day 0 (Pre Dose 1) and Day 120 (Pre Dose 5) | 
| Number of Participants With Positive Anti-Motavizumab Antibodies After Any Dose | The number of participants with positive serum ADA to motavizumab after any dose are reported. | Day 0 (Pre Dose 1) and Day 120 (Pre Dose 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RSV, infants, Native American Indians