Motavizumab Administration for a Second Season for RSV Prophylaxis
Conditions
Keywords
motavizumab, palivizumab, synagis, Rezield, MEDI-524
Brief summary
The primary objective of this study was to determine the effect on immune reactivity to motavizumab (MEDI-524) of monthly intramuscular (IM) doses of motavizumab (MEDI-524) administered for a second season in children.
Detailed description
This was a Phase 1/2, randomized, double-blind study in which motavizumab (MEDI-524) or palivizumab was administered to children who previously participated in MI-CP104. Children who received at least 3 doses of motavizumab in MI-CP104 were eligible for enrollment. Subjects were randomized 1:1 to receive motavizumab or palivizumab at 15 mg/kg by IM injection every 30 days for a total of 4-5 injections during the 2004-05 RSV season subsequent to the season in which they were participants of MI-CP104. All subjects were evaluated prior to and 30 minutes after each injection of study drug with 2 follow-up evaluations, one at 30 days and the other at 90-120 days after the last dose.
Interventions
BIOLOGICALmotavizumab (MEDI-524)
Patients will receive 15 mg/kg MEDI-524 administered IM every 30 days for a total of 4-5 injections.
BIOLOGICALpalivizumab 15 mg/kg
Patients will receive 15 mg/kg palivizumab administered IM every 30 days for a total of 4-5 injections.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Months
Healthy volunteers
No
Inclusion criteria
* Previous participation in MI-CP104 and received at least 3 injections of MEDI-524 in MI-CP104 * The child must be less than or equal to 24 months of age at time of entry into the study (child must be entered on or before their 24-month birthday) * The child must be able to complete the follow-up visits through 3-4 months after last dose (total length of participation of 6-8 months) * Written informed consent obtained from the patient's parent(s) or legal guardian
Exclusion criteria
* Currently hospitalized * Receiving chronic oxygen therapy or mechanical ventilation at the time of study entry (including continuous positive airway pressure \[CPAP\]) * Evidence of infection with hepatitis A, B, or C virus * Known renal impairment, hepatic dysfunction, chronic seizure disorder, or immunodeficiency or HIV infection * Suspected serious allergic or immune mediated events with prior receipt of MEDI-524 * Acute illness or progressive clinical disorder * Active infection, including acute respiratory syncytial virus (RSV) infection at the time of enrollment * Previous reaction to IGIV, blood products, or other foreign proteins * Have ever received palivizumab * Received within the past 120 days or currently receiving immunoglobulin products (such as RSV-IGIV \[RespiGam(R)\], IVIG), or any investigational agents (except MEDI-524) * Currently participating in any investigational study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Exhibiting Anti-motavizumab Antibodies | Day 0 through 120 days post final dose | Serum for measurement of anti-motavizumab antibodies was collected prior to the first, second and, if applicable, fifth doses of study drug, and at the 2 follow-up visits 30 and 90-120 days post final dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Adverse Events (AEs) | Day 0 through 30 days post final dose | Assessments of adverse events (including SAEs) were made by clinical investigators according to the protocol. |
| Number of Subjects Reporting Serious Adverse Events (SAEs) | Day 0 through 30 days post final dose | Assessments of SAEs were made by clinical investigators according to the protocol. |
| Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Day 0 through 30 days post final dose | Serum chemistry and hematology parameters were measured at baseline, on Days 25-30 and 120, 30 days post the final dose, and at premature discontinuation. |
| Motavizumab Serum Concentrations at Each Data Collection Visit | Prior to dosing on Day 0, Day 30, Day 120, and at 30 and 90-120 days post final dose | Mean serum concentration. |
Countries
Brazil, Chile
Participant flow
Recruitment details
Children who received at least 3 doses of motavizumab in Study MI-CP104 during the 2004-2005 RSV season were eligible for enrollment in this study. It was anticipated that approximately 150 children would be enrolled.
Pre-assignment details
Motavizumab or palivizumab was administered to children, using a 1:1 randomization, at 15 mg/kg of study drug by IM injection every 30 days, for a total of 4-5 doses (determined by when in the RSV season a child was enrolled) during the 2005-2006 RSV season.
Participants by arm
| Arm | Count |
|---|---|
| Motavizumab (MEDI-524) 15 mg/kg A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | 66 |
| Palivizumab 15 mg/kg A single intramuscular injection every 30 days for a total of 4-5 injections determined by when in the RSV season a child was enrolled. | 70 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Motavizumab (MEDI-524) 15 mg/kg | Palivizumab 15 mg/kg | Total |
|---|---|---|---|
| Age Continuous | 13.25 Months STANDARD_DEVIATION 3.13 | 13.59 Months STANDARD_DEVIATION 2.89 | 13.43 Months STANDARD_DEVIATION 3 |
| Race/Ethnicity, Customized Hispanic | 61 participants | 62 participants | 123 participants |
| Race/Ethnicity, Customized Other | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized White/Non-Hispanic | 5 participants | 6 participants | 11 participants |
| Sex: Female, Male Female | 23 Participants | 32 Participants | 55 Participants |
| Sex: Female, Male Male | 43 Participants | 38 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 66 | 62 / 70 |
| serious Total, serious adverse events | 4 / 66 | 1 / 70 |
Outcome results
Primary
Number of Subjects Exhibiting Anti-motavizumab Antibodies
Serum for measurement of anti-motavizumab antibodies was collected prior to the first, second and, if applicable, fifth doses of study drug, and at the 2 follow-up visits 30 and 90-120 days post final dose.
Time frame: Day 0 through 120 days post final dose
Population: All subjects who received any study drug were included in all summaries of immunogenicity. Day 0 n=66 mota, n=70 pali; Day 25-30 n=65 mota, n=69 pali; Day 120 n=64 mota, n=67 pali; 30 days post final dose n=65 mota, n=67 pali; 90-120 days post final dose n=64 mota, n=67 pali; at any time n=66 mota, n=70 pali.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | 30 Days Post Final Dose | 0 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | At any time | 2 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | Day 120 | 0 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | Day 0 | 2 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | 90-120 Days Post Final Dose | 0 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | Day 25-30 | 0 participants |
| Palivizumab 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | 90-120 Days Post Final Dose | 10 participants |
| Palivizumab 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | Day 120 | 6 participants |
| Palivizumab 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | 30 Days Post Final Dose | 9 participants |
| Palivizumab 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | Day 25-30 | 3 participants |
| Palivizumab 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | At any time | 12 participants |
| Palivizumab 15 mg/kg | Number of Subjects Exhibiting Anti-motavizumab Antibodies | Day 0 | 3 participants |
Secondary
Motavizumab Serum Concentrations at Each Data Collection Visit
Mean serum concentration.
Time frame: Prior to dosing on Day 0, Day 30, Day 120, and at 30 and 90-120 days post final dose
Population: All subjects who received any study drug were included in all summaries. Day 0 n= 66; Day 25-30 n=65; Day 120 n=63; 30 days post final dose n=63; 90-120 days post final dose n=62
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Motavizumab (MEDI-524) 15 mg/kg | Motavizumab Serum Concentrations at Each Data Collection Visit | Day 0 | 1.536 ug/mL | Standard Deviation 6.192 |
| Motavizumab (MEDI-524) 15 mg/kg | Motavizumab Serum Concentrations at Each Data Collection Visit | Day 25-30 | 54.59 ug/mL | Standard Deviation 16.05 |
| Motavizumab (MEDI-524) 15 mg/kg | Motavizumab Serum Concentrations at Each Data Collection Visit | Day 120 | 86.21 ug/mL | Standard Deviation 23.79 |
| Motavizumab (MEDI-524) 15 mg/kg | Motavizumab Serum Concentrations at Each Data Collection Visit | 30 Days Post Final Dose | 76.03 ug/mL | Standard Deviation 27.13 |
| Motavizumab (MEDI-524) 15 mg/kg | Motavizumab Serum Concentrations at Each Data Collection Visit | 90-120 Days Post Final Dose | 12.2 ug/mL | Standard Deviation 6.26 |
Secondary
Number of Subjects Reporting Adverse Events (AEs)
Assessments of adverse events (including SAEs) were made by clinical investigators according to the protocol.
Time frame: Day 0 through 30 days post final dose
Population: All subjects who received any study drug were included in all summaries of safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects Reporting Adverse Events (AEs) | 56 participants |
| Palivizumab 15 mg/kg | Number of Subjects Reporting Adverse Events (AEs) | 62 participants |
Secondary
Number of Subjects Reporting Serious Adverse Events (SAEs)
Assessments of SAEs were made by clinical investigators according to the protocol.
Time frame: Day 0 through 30 days post final dose
Population: All subjects who received any study drug were included in all summaries of safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects Reporting Serious Adverse Events (SAEs) | 4 participants |
| Palivizumab 15 mg/kg | Number of Subjects Reporting Serious Adverse Events (SAEs) | 1 participants |
Secondary
Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations
Serum chemistry and hematology parameters were measured at baseline, on Days 25-30 and 120, 30 days post the final dose, and at premature discontinuation.
Time frame: Day 0 through 30 days post final dose
Population: All subjects who received any study drug were included in all summaries of safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | ALT Increased | 1 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Neutropenia | 0 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Anemia | 3 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | AST increased | 0 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Blood Urea Nitrogen Increased | 0 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Hemoglobin Decreased | 1 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Eosinophil Count Increased | 0 participants |
| Motavizumab (MEDI-524) 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Eosinophilia | 3 participants |
| Palivizumab 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Eosinophilia | 4 participants |
| Palivizumab 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | ALT Increased | 0 participants |
| Palivizumab 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Blood Urea Nitrogen Increased | 4 participants |
| Palivizumab 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Anemia | 3 participants |
| Palivizumab 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Eosinophil Count Increased | 2 participants |
| Palivizumab 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Neutropenia | 2 participants |
| Palivizumab 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | AST increased | 2 participants |
| Palivizumab 15 mg/kg | Number of Subjects With Increased Toxicity Grade From Baseline as Determined by Laboratory Evaluations | Hemoglobin Decreased | 0 participants |