The major changes were below: Updated for clinical experience with MEDI-524. Updated study objective and overview as - increased monitoring for RSV hospitalizations and medically attended outpatient LRI; the addition of monitoring for non-medically attended wheezing episodes in children who have experienced 3 prior medically attended wheezing episodes while on the study. 1) Routine Visits: Timing of the screening visit was changed from Day 0" to "within 60 days before Study Day 0. 2) Follow-up/Evaluations of Lower Respiratory infection (LRI), Wheezing, OM and Respiratory Hospitalizations. 3) Safety Assessment: This was modified as the point of contact for serious adverse event reporting and as the party responsible for the day-today safety monitoring of the study.

The overall reason for the amendment was to include the following changes 1) Study Design Changes: Dosing with study drug was changed; The sample size was changed; The time period for enrolment was changed; A futility assessment was added; An additional analysis was added, to determine if RSV immunoprophylaxis during the first RSV season; comparison of the incidence and frequency of wheezing and LRI were changed; The time period for collection of the following information was changed.

The overall reason for the amendment was to include the following changes 1) Regarding comparison of the incidence and frequency of medically attended LRIs and wheezing was reworded to only assess LRIs. 2) An assessment of the blinded events rates was to be conducted after the third season to determine if a fourth season of enrollment was needed to achieve primary and secondary objectives. 3) Respiratory Secretions for RSV Detection: all future testing of respiratory secretions for RSV be conducted by qPCR.

The overall reason for the amendment was to include the following changes 1) Routine Visits and Follow-up through Study Day 150: This was updated to add that cord blood can only be used to obtain Study Day 0 results if the child was enrolled by 7 days of age. 2) Final Visit for Patients who prematurely discontinue from the Study: This was revised to clarify that the investigator, not the sponsor, is responsible for requesting permission to continue follow-up.

The overall reason for the amendment was to include the following changes 1) Rationale for Study: To detail the conduct and rationale of an interim analysis and possible unbinding of data. 2) Secondary Objectives: “the incidence of asthma in children at 5 years of age who received motavizumab or placebo,” and renumbering the objectives based on collection of the data. 3) Blinding: This was revised by removing all reference to the DMC, and adding details of the potential unbinding to analyse primary endpoints and secondary endpoints of medically attended LRI and OM, pharmacokinetics, immunogenicity. 4) Administration of Study Drug: This was revised by clarifying when it may be appropriate for subsequent injections to be given in the same site. 5) Routine Visits and Follow-up through Study Day 150: Pre-dose vital sign measurement was extended to within 60 minutes prior to drug dose. 6) Pulmonary Function Measures: revised by specifying that pulmonary function tests will continue unless the analysis of wheezing through 3 years suggests that evaluating. 7) Safety Management during the Study was included. 8) Sample Size: revised to reflect the updated protocol strategy of conducting an interim analysis.

The overall reason for the amendment was to include the following changes 1) Secondary Objectives: changed from “in first Respiratory Syncytia Virus (RSV) season” to “through Day 150”; added “in patients enrolled in seasons 1-3 only”; changed “3 years of follow-up” to “3 years of age”. 2) Changes in Study design and eligibility criteria. 3) Follow-up/Evaluation of LRI, Wheezing, OM, and Respiratory Hospitalizations. 4) Final Visit for Patients who Prematurely Discontinue from the Study changed assessment of medically attended acute Lower Respiratory infection (LRI) to occur if discontinuation occurs prior to Study Day 150 but not if discontinuation occurs prior to 3 years of age. 5) Added “central RT-PCR” were added to specify the type of RSV test and changed “within 3 days of hospitalization”. 6) Clarified that the IHS physician are primary care physicians. 7) A note was added that Respiratory Secretions for RSV Detection. 8) Routine Laboratory Evaluations: Clarified that blood samples will only be collected in seasons 1, 2, and 3. 9) Medically Attended Acute Respiratory Illnesses: Clarified that patients in seasons 1 and 2 will be followed for 3 years on study. 10) Wheezing Episode Changed from 5 years to 3 years; Changed “research assistant” to “study staff member”. 11) Pharmacokinetic and Immunologic Evaluations. 12) Pulmonary Function Test (PFT) measures were deleted. 13) Completion of Primary Study and Loss to Follow-up. 14) Study Reporting Period for Serious Adverse Events. 15) Interruption of Discontinuation of Study Dosing in Individual Patients: Changed from 5 years to 3 years of age. 16) Secondary Endpoints: Clarified that 150 days is from randomization and change 3 years of follow-up to 3 years of age and delete the asthma assessment at age 5.