Congenital Heart Disease
Conditions
Keywords
Synagis, motavizumab, palivizumab, children, MEDI-524, RSV, congenital hear disease
Brief summary
The primary goal was to describe the safety of the investigational product when given monthly to prevent serious respiratory infection among children with significant heart disease.
Detailed description
The primary objective was to describe the safety and tolerability of motavizumab when given monthly as prophylaxis against serious RSV infection among children with hemodynamically significant congenital heart disease.
Interventions
BIOLOGICALMotavizumab
15 mg/kg IM administered at monthly intervals
BIOLOGICALPalivizumab
15 mg/kg IM administered at monthly intervals
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
* 24 months of age or younger at randomization (child must have been randomized on or before their 24-month birthday) * Documented, hemodynamically significant CHD * Unoperated or partially corrected CHD * Written informed consent obtained from the patient's parent(s)/legal guardian(s) Note: The following children were not eligible: children with uncomplicated small atrial or ventricular septal defects or patent ductus arteriosus, children with aortic stenosis, pulmonic stenosis, or coarctation of the aorta alone. Children with acyanotic cardiac lesions must have pulmonary hypertension \[≥ 40 mmHg measured pressure in the pulmonary artery (PA)\] or the need for daily medication to manage CHD.
Exclusion criteria
* Unstable cardiac or respiratory status, including cardiac defects so severe that survival was not expected or for which cardiac transplantation was planned or anticipated * Hospitalization, unless discharge was anticipated within 21 days * Anticipated cardiac surgery within two weeks of randomization * Requirement for mechanical ventilation, extracorporeal membrane oxygenation, continuous positive airway pressure or other mechanical respiratory or cardiac support * Associated non-cardiac anomalies or end organ dysfunction resulting in anticipated survival of less than six months or unstable abnormalities of end organ function * Acute respiratory illness, or other acute infection or illness Note: children with any respiratory symptoms must have had a negative RSV test prior to randomization * Chronic seizure or evolving or unstable neurologic disorder * Known immunodeficiency * Mother with HIV infection (unless the child had been proven to be not infected) * Known allergy to Ig products * Receipt of any polyclonal antibody (for example, Hepatitis B IG, IVIG, VZIG) within 3 months prior to randomization * Receipt of palivizumab (Synagis®) within 3 months prior to randomization * Use of investigational agents within the past three months (other than investigational agents commonly used during cardiac surgery or the immediate post-operative period, e.g., nitric oxide) * Current participation in other investigational protocols of drugs or biological agents * Previous participation in MI-CP124 (Season 1)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Adverse Events Through Study Day 150 | Days 0-150 | Adverse events were summarized by system organ class (SOC) and preferred term (using MedDRA Version 11.1) overall. |
| Number of Subjects Reporting Serious Adverse Events Through Study Day 150 | Days 0-150 | Serious adverse events were those that resulted in death; were life-threatening; resulted in subject hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed above. |
| Number of Subjects Reporting Laboratory Adverse Events | Days 0-150 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Trough Serum Concentration of Motavizumab at Pre-dose 1 | Pre-dose 1 | Trough serum concentrations (ug/mL) of motavizumab at pre-dose 1 |
| Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 1 | 30 days post-dose 1 | Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 1 |
| Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 2 | 30 days post-dose 2 | Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 2 |
| The Number of Subjects Hospitalized for RSV Infection. | Days 0-150 | An RSV hospitalization was defined as one of the following: 1) Cardiac/respiratory hospitalization with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory, or 2) New onset of lower respiratory tract symptoms with an objective measure of worsening respiratory status in an already hospitalized subject with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory (nosocomial RSV hospitalization), or 3) Death demonstrated to be caused by RSV (based on virologic evidence and either clinical history or autopsy). |
| Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 4 | 30 days post-dose 4 | Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 4 |
| Mean Trough Serum Concentrations of Motavizumab in Subjects Who Underwent Cardiac Surgery With Cardiopulmonary Bypass | Days 0-150 | Subjects who underwent cardiac surgery with cardiopulmonary bypass through Study Day 150 were to have a blood sample taken for determination of study drug concentrations prior to receipt of another dose of study drug immediately following surgery. |
| Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 3 | 30 days post-dose 3 | Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 3 |
| The Number of Subjects With RSV Outpatient MA-LRI for Season 2 Only. | Days 0-150 | An RSV outpatient MA-LRI was defined as an outpatient medically-attended event designated by the principal investigator as a lower respiratory illness with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory. |
| Number of Subjects Who Had Anti-motavizumab Antibodies Detected | Days 0-150 | ECLA-based method |
Countries
Austria, Belgium, Bulgaria, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Lebanon, Poland, Russia, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
A total of 1236 subjects were randomized at 162 sites in 16 countries within the northern hemisphere between 21Oct2005 and 14Dec2005 in Season 1 and 02Oct2007 and 31Dec2007 in Season 2; each subject participated in the study for a single RSV season.
Pre-assignment details
Subjects were randomized 1:1 on Study Day 0 to receive either 15 mg/kg motavizumab or 15 mg/kg palivizumab. A permuted-block randomization method was used and a separate randomization schedule was generated for each site and cyanotic CHD strata combination.
Participants by arm
| Arm | Count |
|---|---|
| Motavizumab (MEDI-524) Motavizumab was administered as an intramuscular injection at 15 mg/kg every 30 days during the RSV season for a total of 5 scheduled injections. Additionally, children who underwent cardiac surgery with cardiopulmonary bypass through Study Day 150 were to receive a protocol-specified replacement dose of study drug immediately following the surgery when determined by the physician to be medically stable for an IM injection. | 623 |
| Palivizumab Palivizumab was administered as an intramuscular injection at 15 mg/kg every 30 days during the RSV season for a total of 5 scheduled injections. Additionally, children who underwent cardiac surgery with cardiopulmonary bypass through Study Day 150 were to receive a protocol-specified replacement dose of study drug immediately following the surgery when determined by the physician to be medically stable for an IM injection. | 612 |
| Total | 1,235 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 9 | 10 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal of consent | 9 | 7 |
Baseline characteristics
| Characteristic | Motavizumab (MEDI-524) | Total | Palivizumab |
|---|---|---|---|
| Age Continuous | 8.47 months STANDARD_DEVIATION 6.4 | 8.33 months STANDARD_DEVIATION 6.45 | 8.18 months STANDARD_DEVIATION 6.51 |
| Race/Ethnicity, Customized Asian | 10 participants | 18 participants | 8 participants |
| Race/Ethnicity, Customized Black | 23 participants | 43 participants | 20 participants |
| Race/Ethnicity, Customized Hispanic | 21 participants | 44 participants | 23 participants |
| Race/Ethnicity, Customized Other | 29 participants | 61 participants | 32 participants |
| Race/Ethnicity, Customized White/Non-hispanic | 540 participants | 1069 participants | 529 participants |
| Region of Enrollment Austria | 7 participants | 14 participants | 7 participants |
| Region of Enrollment Belgium | 28 participants | 54 participants | 26 participants |
| Region of Enrollment Bulgaria | 18 participants | 36 participants | 18 participants |
| Region of Enrollment Canada | 27 participants | 49 participants | 22 participants |
| Region of Enrollment Czech Republic | 35 participants | 74 participants | 39 participants |
| Region of Enrollment France | 13 participants | 28 participants | 15 participants |
| Region of Enrollment Germany | 35 participants | 66 participants | 31 participants |
| Region of Enrollment Hungary | 27 participants | 53 participants | 26 participants |
| Region of Enrollment Israel | 67 participants | 132 participants | 65 participants |
| Region of Enrollment Lebanon | 62 participants | 128 participants | 66 participants |
| Region of Enrollment Poland | 50 participants | 99 participants | 49 participants |
| Region of Enrollment Russian Federation | 32 participants | 66 participants | 34 participants |
| Region of Enrollment Spain | 31 participants | 57 participants | 26 participants |
| Region of Enrollment Sweden | 10 participants | 21 participants | 11 participants |
| Region of Enrollment United Kingdom | 26 participants | 57 participants | 31 participants |
| Region of Enrollment United States | 155 participants | 301 participants | 146 participants |
| Sex: Female, Male Female | 282 Participants | 580 Participants | 298 Participants |
| Sex: Female, Male Male | 341 Participants | 655 Participants | 314 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 553 / 618 | 540 / 612 |
| serious Total, serious adverse events | 292 / 618 | 304 / 612 |
Outcome results
Primary
Number of Subjects Reporting Adverse Events Through Study Day 150
Adverse events were summarized by system organ class (SOC) and preferred term (using MedDRA Version 11.1) overall.
Time frame: Days 0-150
Population: The Safety population included all subjects who received any study drug and had any safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524) | Number of Subjects Reporting Adverse Events Through Study Day 150 | 575 participants |
| Palivizumab | Number of Subjects Reporting Adverse Events Through Study Day 150 | 566 participants |
Primary
Number of Subjects Reporting Laboratory Adverse Events
Time frame: Days 0-150
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Aspartate aminotransferase increased | 3 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Hepatic enzyme increased | 3 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood sodium abnormal | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Hyperbilirubinemia | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood calcium decreased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Hypertransaminasemia | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood sodium decreased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Hypothyroidism | 3 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Anemia | 17 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | International normalised ratio decreased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood thyroid stimulating hormone increased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | International normalised ratio increased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood calcium increased | 2 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Iron deficiency anaemia | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood urea increased | 39 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Liver function test abnormal | 3 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Bacteria sputum indentified | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Mean cell volume decreased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Brain natriuretic peptide increased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Neutropenia | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood creatinine increased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Occult blood positive | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | C-reactive protein increased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Oxygen saturation decreased | 9 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Alanine aminotranferase increased | 13 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Platelet count decreased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Clostridium difficiline toxin test positive | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Renal function test abnormal | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood potassium decreased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Thrombocythemia | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Coagulation test abnormal | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Thrombocytopenia | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood alkaline phosphatase increased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Thyroid function test abnormal | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Haematocrit drecreased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Transaminases increased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Blood potassium increased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Urine output decreased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Haemaglobin decreased | 0 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | White blood cell count increased | 1 participants |
| Motavizumab (MEDI-524) | Number of Subjects Reporting Laboratory Adverse Events | Adrenal insufficiency | 3 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | White blood cell count increased | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Adrenal insufficiency | 3 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Alanine aminotranferase increased | 26 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Anemia | 14 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Aspartate aminotransferase increased | 9 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Bacteria sputum indentified | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood alkaline phosphatase increased | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood calcium decreased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood calcium increased | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood creatinine increased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood potassium decreased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood potassium increased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood sodium abnormal | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood sodium decreased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood thyroid stimulating hormone increased | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Blood urea increased | 34 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Brain natriuretic peptide increased | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | C-reactive protein increased | 5 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Clostridium difficiline toxin test positive | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Coagulation test abnormal | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Haematocrit drecreased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Haemaglobin decreased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Hepatic enzyme increased | 3 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Hyperbilirubinemia | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Hypertransaminasemia | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Hypothyroidism | 2 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | International normalised ratio decreased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | International normalised ratio increased | 2 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Iron deficiency anaemia | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Liver function test abnormal | 2 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Mean cell volume decreased | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Neutropenia | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Occult blood positive | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Oxygen saturation decreased | 4 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Platelet count decreased | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Renal function test abnormal | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Thrombocythemia | 0 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Thrombocytopenia | 5 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Thyroid function test abnormal | 1 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Transaminases increased | 2 participants |
| Palivizumab | Number of Subjects Reporting Laboratory Adverse Events | Urine output decreased | 1 participants |
Primary
Number of Subjects Reporting Serious Adverse Events Through Study Day 150
Serious adverse events were those that resulted in death; were life-threatening; resulted in subject hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability or incapacity; or were an important medical event that may not have resulted in death, threatened life, or required hospitalization and that, based on appropriate medical judgment, may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: Days 0-150
Population: The Safety population included all subjects who received any study drug and had any safety follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524) | Number of Subjects Reporting Serious Adverse Events Through Study Day 150 | 292 participants |
| Palivizumab | Number of Subjects Reporting Serious Adverse Events Through Study Day 150 | 304 participants |
Secondary
Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 1
Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 1
Time frame: 30 days post-dose 1
Population: Evaluable for PK population; all motavizumab-treated subjects who received any study drug and did not received commercial palivizumab. Excludes subjects after cardiopulmonary bypass surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motavizumab (MEDI-524) | Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 1 | 46.90 ug/mL | Standard Deviation 15.2 |
Secondary
Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 2
Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 2
Time frame: 30 days post-dose 2
Population: Evaluable for PK population; all motavizumab-treated subjects who received any study drug and did not received commercial palivizumab. Excludes subjects after cardiopulmonary bypass surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motavizumab (MEDI-524) | Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 2 | 60.94 ug/mL | Standard Deviation 25.41 |
Secondary
Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 3
Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 3
Time frame: 30 days post-dose 3
Population: Evaluable for PK population; all motavizumab-treated subjects who received any study drug and did not received commercial palivizumab. Excludes subjects after cardiopulmonary bypass surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motavizumab (MEDI-524) | Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 3 | 66.59 ug/mL | Standard Deviation 34.51 |
Secondary
Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 4
Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 4
Time frame: 30 days post-dose 4
Population: Evaluable for PK population; all motavizumab-treated subjects who received any study drug and did not received commercial palivizumab. Excludes subjects after cardiopulmonary bypass surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motavizumab (MEDI-524) | Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 4 | 77.87 ug/mL | Standard Deviation 32.75 |
Secondary
Mean Trough Serum Concentration of Motavizumab at Pre-dose 1
Trough serum concentrations (ug/mL) of motavizumab at pre-dose 1
Time frame: Pre-dose 1
Population: Evaluable for PK population; all motavizumab-treated subjects who received any study drug and did not received commercial palivizumab. Excludes subjects after cardiopulmonary bypass surgery.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motavizumab (MEDI-524) | Mean Trough Serum Concentration of Motavizumab at Pre-dose 1 | 0.0 ug/mL | Standard Deviation 0 |
Secondary
Mean Trough Serum Concentrations of Motavizumab in Subjects Who Underwent Cardiac Surgery With Cardiopulmonary Bypass
Subjects who underwent cardiac surgery with cardiopulmonary bypass through Study Day 150 were to have a blood sample taken for determination of study drug concentrations prior to receipt of another dose of study drug immediately following surgery.
Time frame: Days 0-150
Population: Evaluable for PK following cardiac surgery with cardiopulomonary bypass; all motivizumab treated subjects who underwent cardiac surgery with cardiopulmonary bypass and who received the correct dose regiment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Motavizumab (MEDI-524) | Mean Trough Serum Concentrations of Motavizumab in Subjects Who Underwent Cardiac Surgery With Cardiopulmonary Bypass | 48.51 ug/mL | Standard Deviation 27.3 |
Secondary
Number of Subjects Who Had Anti-motavizumab Antibodies Detected
ECLA-based method
Time frame: Days 0-150
Population: Evaluable for ADA Population; includes all motavizumab-treated subjects who received the correct study drug for their first dose and did not receive commercial palivizumab before receiving any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524) | Number of Subjects Who Had Anti-motavizumab Antibodies Detected | 9 participants |
Secondary
The Number of Subjects Hospitalized for RSV Infection.
An RSV hospitalization was defined as one of the following: 1) Cardiac/respiratory hospitalization with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory, or 2) New onset of lower respiratory tract symptoms with an objective measure of worsening respiratory status in an already hospitalized subject with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory (nosocomial RSV hospitalization), or 3) Death demonstrated to be caused by RSV (based on virologic evidence and either clinical history or autopsy).
Time frame: Days 0-150
Population: The ITT population is the primary efficacy analysis population and consists of all subjects randomized into the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524) | The Number of Subjects Hospitalized for RSV Infection. | 12 participants |
| Palivizumab | The Number of Subjects Hospitalized for RSV Infection. | 16 participants |
Comparison: Relative risk and confidence interval adjusted for the stratification factor of CHD stratum (cyanotic or other) specified on the CRF95% CI: [0.344, 1.586]Guess method
Secondary
The Number of Subjects With RSV Outpatient MA-LRI for Season 2 Only.
An RSV outpatient MA-LRI was defined as an outpatient medically-attended event designated by the principal investigator as a lower respiratory illness with a positive real-time RT-PCR RSV diagnostic test performed at a central laboratory.
Time frame: Days 0-150
Population: All subjects who were randomized in Season 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524) | The Number of Subjects With RSV Outpatient MA-LRI for Season 2 Only. | 3 participant |
| Palivizumab | The Number of Subjects With RSV Outpatient MA-LRI for Season 2 Only. | 6 participant |
Comparison: Relative risk and confidence interval adjusted for the stratification factor of CHD stratum (cyanotic or other) specified on the CRF95% CI: [0.101, 1.989]Guess method