Chronic Lung Disease
Conditions
Brief summary
The purpose of this study is to measure the rate of anti-palivizumab antibodies (also referred to as immune reactivity or immunogenicity) in subjects receiving either the liquid or lyophilized formulation of palivizumab. This study will compare the number and percentage of subjects with anti-palivizumab antibodies receiving either the liquid or lyophilized formulation of palivizumab.
Detailed description
The approved liquid formulation of palivizumab was developed to simplify preparation of the drug before injection. Both formulations of palivizumab have been shown to be bioequivalent in children 6 months of age or younger with a history of chronic lung disease. In previous studies of liquid palivizumab, immunogenicity was evaluated up to 2 months after dosing in adults, and 1 month after dosing in children. In this study, MI-CP116, immunogenicity will be evaluated between 4 and 6 months after the last dose of study drug, in order to provide data at a time point significantly distant from dosing when drug interference is minimal.
Interventions
BIOLOGICALLyophilized Palivizumab
Patients will receive 15 mg/kg of lyophilized palivizumab administered intramuscularly every 30 days for a total of 5 injections.
BIOLOGICALLiquid Palivizumab
Patients will receive 15 mg/kg of liquid palivizumab administered intramuscularly every 30 days for a total of 5 injections.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Months
Healthy volunteers
No
Inclusion criteria
* Medically stable child with chronic lung disease of prematurity who is ≤24 months of age at randomization OR child with premature birth (gestational age ≤35 weeks or less) and who is 6 months of age or younger at randomization * Written informed consent obtained from the patient's parent(s) or legal guardian(s) * The child must be able to complete the follow-up visit 4-6 months after the last dose of study drug
Exclusion criteria
* Hospitalization at the time of randomization (unless discharge is anticipated within 3 weeks) * Be receiving mechanical ventilation at the time of study entry (including CPAP) * Congenital heart disease (children with uncomplicated CHD \[e.g., PDA, small septal defect\] and children with complicated CHD who are currently anatomically and hemodynamically normal can be enrolled). * Mother with HIV infection (unless the child has been proven to be not infected) * Life expectancy \<6 months * Known allergy to Ig products * Acute respiratory or other acute infection or illness * Previous reaction to IGIV, blood products, or other foreign proteins * Receipt of lyophilized palivizumab, RSV-IG IV, or other RSV-specific monoclonal antibody, or any other polyclonal antibody (for example, Hepatitis B IG, IVIG, VZIG) within 3 months prior to randomization * Any previous receipt of MEDI-524 * Participation in other investigational drug product studies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants With Immune Reactivity | Day 240-300 follow up | Presence of anti-palivizumab antibodies |
Countries
United States
Participant flow
Recruitment details
A total of 417 subjects were randomized into the study at 51 sites in the United States between 20 October 2005 and 02 October 2007.
Pre-assignment details
A total of 4 subjects at site #1022 who received all 5 doses of study drug (per drug accountability records) had no further information including case report form that could be obtained. These 4 subjects were excluded from all data analyses.
Participants by arm
| Arm | Count |
|---|---|
| Liquid Palivizumab Liquid Palivizumab, 15 mg/kg IM q30 days X 5 | 211 |
| Lyophilized Palivizumab Lyophilized Palivizumab, 15 mg/kg IM q30 days X 5 | 202 |
| Total | 413 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 7 | 7 |
| Overall Study | Moved to Dom. Republic | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Relocation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | Total | Liquid Palivizumab | Lyophilized Palivizumab |
|---|---|---|---|
| Age, Continuous | 4.29 months STANDARD_DEVIATION 4.34 | 4.56 months STANDARD_DEVIATION 4.5 | 4.00 months STANDARD_DEVIATION 4.16 |
| Chronic Lung Disease at Prematurity No | 352 Participants | 176 Participants | 176 Participants |
| Chronic Lung Disease at Prematurity Yes | 61 Participants | 35 Participants | 26 Participants |
| Gestational Age at Birth | 32.5 Weeks STANDARD_DEVIATION 2.6 | 32.4 Weeks STANDARD_DEVIATION 2.7 | 32.7 Weeks STANDARD_DEVIATION 2.5 |
| Race/Ethnicity American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity Asian | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity Black or African American | 49 Participants | 25 Participants | 24 Participants |
| Race/Ethnicity Hispanic | 36 Participants | 22 Participants | 14 Participants |
| Race/Ethnicity More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity Other | 24 Participants | 12 Participants | 12 Participants |
| Race/Ethnicity Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity White | 300 Participants | 151 Participants | 149 Participants |
| Region of Enrollment United States | 413 participants | 211 participants | 202 participants |
| Sex: Female, Male Female | 203 Participants | 104 Participants | 99 Participants |
| Sex: Female, Male Male | 210 Participants | 107 Participants | 103 Participants |
| Weight at Day 0 | 5.205 Kilogram STANDARD_DEVIATION 2.27 | 5.326 Kilogram STANDARD_DEVIATION 2.274 | 5.079 Kilogram STANDARD_DEVIATION 2.264 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 211 | 0 / 202 |
| serious Total, serious adverse events | 18 / 211 | 12 / 202 |
Outcome results
Primary
Number and Percentage of Participants With Immune Reactivity
Presence of anti-palivizumab antibodies
Time frame: Day 240-300 follow up
Population: Participants who received at least 2 doses of study drug and had at least 1 blood sample collected (at baseline or Study Day 240-300) were included in the analysis. This included 206 subjects in Arm 1 and 200 subjects in Arm 2. Of these subjects, 191 (Arm 1) and 188 (Arm 2) had adequate blood samples for analysis. This analysis was per protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liquid Palivizumab | Number and Percentage of Participants With Immune Reactivity | Number | 0 Participants |
| Liquid Palivizumab | Number and Percentage of Participants With Immune Reactivity | Percentage | 0.0 Participants |
| Lyophilized Palivizumab | Number and Percentage of Participants With Immune Reactivity | Number | 1 Participants |
| Lyophilized Palivizumab | Number and Percentage of Participants With Immune Reactivity | Percentage | 0.5 Participants |
| Combined Liquid/Lyophilized Palivizumab | Number and Percentage of Participants With Immune Reactivity | Number | 1 Participants |
| Combined Liquid/Lyophilized Palivizumab | Number and Percentage of Participants With Immune Reactivity | Percentage | 0.3 Participants |
Comparison: The subject number of 200 per treatment group was derived to demonstrate a percentage of immune reactivity in either the liquid or lyophilized formulations of palivizumab of \<2-3% based on 95% confidence intervals \[(0%; 0.00, 1.83), (0.5%; 0.01, 2.75), (1%; 0.12, 3.57)\].95% CI: [0, 1.9]
Comparison: The subject number of 200 per treatment group was derived to demonstrate a percentage of immune reactivity in either the liquid or lyophilized formulations of palivizumab of \<2-3% based on 95% confidence intervals \[(0%; 0.00, 1.83), (0.5%; 0.01, 2.75), (1%; 0.12, 3.57)\].95% CI: [0, 2.9]
Comparison: The subject number of 200 per treatment group was derived to demonstrate a percentage of immune reactivity in either the liquid or lyophilized formulations of palivizumab of \<2-3% based on 95% confidence intervals \[(0%; 0.00, 1.83), (0.5%; 0.01, 2.75), (1%; 0.12, 3.57)\].95% CI: [0, 1.5]