Study of Motavizumab (MEDI-524) and Palivizumab Administered Sequentially in the Same Respiratory Syncytial Virus (RSV) Season

Study Overview
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Brief Summary
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This is a Phase 2, randomized, double-blind study in which motavizumab (MEDI-524) and palivizumab were administered sequentially to high-risk children during the same respiratory syncytial virus (RSV) season. A control group was administered only motavizumab.

Detailed Description
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This is a Phase 2, randomized, double-blind study in which motavizumab and palivizumab were administered sequentially to high-risk children during the same RSV season. It was anticipated that approximately 240 children (80 in each group) would be enrolled from the southern hemisphere during the upcoming RSV season (2006). Children were randomized into one of three regimens in a 1:1:1 ratio; the first group received 2 doses of motavizumab followed by 3 doses of palivizumab; the second group received 2 doses of palivizumab followed by 3 doses of motavizumab; and the third group received 5 doses of motavizumab. Motavizumab or palivizumab was administered at 15 mg/kg by IM injection every 30 days, for a total of 5 injections.

Official Title
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A Phase 2, Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of Motavizumab (MEDI-524), a Humanized Enhanced Potency Monoclonal Antibody Against Respiratory Syncytial Virus (RSV), and Palivizumab When Administered in the Same Season

Conditions
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Respiratory Syncytial Virus Infections, Chronic Lung Disease and <= 24 Months of Age or, Premature With Gestational Age <=35 Weeks and <=6 Months of Age

Intervention / Treatment
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* Biological: Motavizumab, palivizumab
* Biological: Palivizumab, motavizumab
* Biological: Motavizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The child must have been born at less than or equal to 35 weeks gestation and be less than or equal to 6 months of age at the time of entry into the study (child must be entered on or before his/her 6-month birthday); or the child must be less than or equal to 24 months of age at the time of entry into the study (child must be entered on or before his/her 24-month birthday) and diagnosed with chronic lung disease (CLD) of prematurity with stable or decreasing doses of diuretics, steroids, or bronchodilators, or treatment with supplemental oxygen, within the previous 6 months. The child must be in general good health at the time of study entry. The child's parent(s)/legal guardian must provide written informed consent. The child must be able to complete the follow-up visits through 120-150 days from last injection of study drug. Parent(s)/legal guardian of patient must have available telephone access. Exclusion Criteria: Hospitalized at the time of study entry (unless discharge is expected within 10 days after entry into the study) Receiving chronic oxygen therapy or mechanical ventilation at the time of study entry (including continuous positive airway pressure [CPAP]) Congenital heart disease (CHD) (children with medically or surgically corrected [closed] patent ductus arteriosus and no other CHD may be enrolled) Evidence of infection with hepatitis A, B, or C virus Known renal impairment, hepatic dysfunction, chronic seizure disorder, or immunodeficiency or HIV infection (a child of a mother with known HIV infection must be proven to be uninfected at the time of enrollment) Suspected serious allergic or immune-mediated events with prior receipt of palivizumab Acute illness or progressive clinical disorder Active infection, including acute RSV infection, at the time of enrollment Previous reaction to intravenous immunoglobulin (IGIV), blood products, or other foreign proteins Received within the past 120 days or currently receiving immunoglobulin products (such as RSV-IGIV [RespiGam], IVIG, or palivizumab) or any investigational agents Previous participation in a clinical trial of motavizumab Currently participating in any investigational study

Ages Eligible for Study
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Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- |
| Experimental: Motavizumab followed by Palivizumab<br>2 doses of motavizumab (15 mg/kg, administered as an intramuscular injection once/month) followed by 3 doses of palivizumab (15 mg/kg, administered as an intramuscular injection once/month) | Biological: Motavizumab, palivizumab<br>* Motavizumab was provided in sterile vials containing 100 mg of motavizumab in 1 mL of a sterile preservative-free liquid product at pH 6.0, formulated with 25 mM histidine-HCl.<br>|
| Experimental: Palivizumab followed by motavizumab<br>2 doses of palivizumab (15 mg/kg, administered as an intramuscular injection once/month) followed by 3 doses of motavizumab (15 mg/kg, administered as an intramuscular injection once/month) | Biological: Palivizumab, motavizumab<br>* Palivizumab was provided in sterile vials containing 100 mg of palivizumab in 1 mL of a sterile preservative-free liquid product at pH 6.0, formulated with 25 mM histidine, and 1.6 mM glycine.<br>|
| Experimental: Motavizumab control<br>5 doses of motavizumab (15 mg/kg, administered as an intramuscular injection once/month) | Biological: Motavizumab<br>* Motavizumab was provided in sterile vials containing 100 mg of motavizumab in 1 mL of a sterile preservative-free liquid product at pH 6.0, formulated with 25 mM histidine-HCl.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Serious Adverse Events (SAEs) |  | Day 0 - Day 150 | 
| Number of Subjects Reporting Adverse Events (AEs) |  | Day 0 - Day 150 | 
| Number of Subjects With Changes in Laboratory Chemistry Values Reported as AEs. | Serum chemistry samples were collected at Day 0, Day 60, and Day 150. Values representing changes in severity according to the AE grading table were recorded as AEs. | Day 0 - Day 150 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Serum Concentrations of Motavizumab at Day 0 |  | Day 0 | 
| The Trough Serum Concentrations of Motavizumab at Day 60 |  | Day 60 | 
| The Trough Serum Concentrations of Motavizumab at Day 150 |  | Day 150 | 
| The Trough Serum Concentrations of Motavizumab 120-150 Days Post Final Dose |  | 120-150 days post final dose | 
| The Serum Concentrations of Palivizumab at Day 0 |  | Day 0 | 
| The Trough Serum Concentrations of Palivizumab at Day 60 |  | Day 60 | 
| The Trough Serum Concentrations of Palivizumab at Day 150 |  | Day 150 | 
| The Trough Serum Concentrations of Palivizumab at 120-150 Days Post Final Dose |  | 120-150 days post final dose | 
| The Immunogenicity of Motavizumab at Day 0 | Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | Day 0 | 
| The Immunogenicity of Motavizumab at Day 60 | Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | Day 60 | 
| The Immunogenicity of Motavizumab at Day 150 | Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | Day 150 | 
| The Immunogenicity of Motavizumab at 120 to 150 Days Post Final Dose | Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | 120 - 150 days post final dose | 
| The Immunogenicity of Motavizumab at Any Time | Number of subjects with detected anti-motavivumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | At any time | 
| The Immunogenicity of Palivizumab at Day 0 | Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | Day 0 | 
| The Immunogenicity of Palivizumab at Day 60 | Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | Day 60 | 
| The Immunogenicity of Palivizumab at Day 150 | Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | Day 150 | 
| The Immunogenicity of Palivizumab at 120 to 150 Days Post Final Dose | Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | 120 - 150 days post final pose | 
| The Immunogenicity of Palivizumab at Any Time | Number of subjects with detected anti-palivizumab antibodies are reported; defined as a titer with a dilution value of greater than or equal to 1:10. | At any time | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Syncytial Virus, Premature and under 6 mos. of age, Chronic Lung Disease over 6 mos. of age, palivizumab, motavizumab, RSV