Respiratory Syncytial Virus Prophylaxis
Conditions
Keywords
MEDI-524, Motavizumab, respiratory syncytial virus, children, intravenous, Rezield
Brief summary
The purpose of this study is to determine the safety of motavizumab (MEDI-524) following a single intravenous dose in children hospitalized with respiratory syncytial virus (RSV).
Detailed description
This study was designed as a Phase 1, randomized, double-blind, placebo-controlled, dose-escalation, multicenter clinical study to evaluate the safety, tolerability, serum concentrations, and immunogenicity of a single intravenous dose of motavizumab (MEDI-524) and the effect on the amount of respirtory syncytial virus (RSV) in the respiratory tract (nasopharynx) of otherwise healthy children hospitalized with RSV infection.
Interventions
BIOLOGICALMotavizumab
Single dose of Motavizumab at a dose of 3 mg/kg administered intravenously (in the vein) on Day 0
OTHERPlacebo
Single dose of placebo administered intravenously (in the vein) on Day 0
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Months
Healthy volunteers
No
Inclusion criteria
* Previously healthy * Age 24 months and younger at the time of randomization * Gestational age of 36 weeks gestation and older * Randomization within 24 hours after hospitalization * Hospitalized for lower respiratory tract illness (ie, respiratory syncytial virus (RSV) bronchiolitis and/or pneumonia) documented by positive RSV antigen detection or culture in respiratory secretions within 72 hours before randomization
Exclusion criteria
* Already received or would receive ribavirin or other anti-viral treatment for the current episode of RSV infection prior to randomization * Required intubation for ventilatory support * Any medically significant underlying ongoing chronic illness or organ system dysfunction or other known acute illness, other than RSV infection * Known renal impairment, hepatic dysfunction, hematologic abnormalities, seizure or other neurologic disorder or immunodeficiency * Requirement for supplemental oxygen at any time prior to the current RSV infection (brief use of oxygen in the immediate postnatal period to treat a transient condition was allowed) * Mechanical ventilation at any time prior to the onset of the current RSV infection * Congenital heart disease (children with medically or surgically corrected patent ductus arteriosus \[PDA\], small atrial septal defect \[ASD\] or ventricular septal defect \[VSD\] were allowed) * Previous reaction to intravneous immunoglobulin (IVIG), blood products, or other foreign proteins * Prior use of IVIG, RSV-IGIV (RespiGam), palivizumab (Synagis), or other immunoglobulin products within the past 2 months * Currently receiving other investigational agents or have received any other investigational agents within the last 3 months * Prior or current participation in any investigational study with a therapeutic agent or vaccine for RSV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Reporting Adverse Events Through 30 Days After Dosing | From the start of treatment to 30 days after dosing | Safety and tolerability of motavizumab (MEDI-524) was measured by adverse events through 30 days after dosing |
| Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing | From the start of treatment to 30 days after dosing | Safety and tolerability of motavizumab (MEDI-524) was measured by serious adverse events through 30 days after dosing |
| The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations | From the start of treatment to 30 days after dosing | Safety and tolerability of motavizumab (MEDI-524) was measured by the occurrence of increased toxicity grade from baseline as determined by laboratory evaluations (complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and urinalysis) at baseline and at each study collection time point following dosing |
| To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Day 2 and Day 30 | Mean trough serum concentrations of motavizumab (MEDI-524) were collected on Day 2 and on Day 30. Serum concentrations of MEDI-524 were analysed using a qualified enzyme-linked immunosorbent assay (ELISA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0 | Immediately before dosing on Day 0 | The serum anti-motavizumab antibody titers were measured in subjects on Day 0 (before dosing). Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay. |
| To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30 | Day 30 | The serum anti-motavizumab antibody titers were measured in subjects on Day 30. Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay. |
Participant flow
Pre-assignment details
The screening period occurred within 24 hours before randomization. All subjects who were screened were randomized into the study.
Participants by arm
| Arm | Count |
|---|---|
| Motavizumab (MEDI-524), 3 mg/kg Motavizumab, 3 mg/kg as a single intravenous dose administered on Day 0 | 5 |
| Motavizumab (MEDI-524), 15 mg/kg Motavizumab, 15 mg/kg as a single intravenous dose administered on Day 0 | 5 |
| Motavizumab (MEDI-524), 30 mg/kg Motavizumab, 30 mg/kg as a single intravenous dose administered on Day 0 | 5 |
| Placebo Placebo, as a single intravenous dose administered on Day 0 | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Dosing window missed | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Motavizumab (MEDI-524), 3 mg/kg | Motavizumab (MEDI-524), 15 mg/kg | Motavizumab (MEDI-524), 30 mg/kg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 8.84 months STANDARD_DEVIATION 6.62 | 3.18 months STANDARD_DEVIATION 1.56 | 10.78 months STANDARD_DEVIATION 9.07 | 7.43 months STANDARD_DEVIATION 7.69 | 7.51 months STANDARD_DEVIATION 7.19 |
| Race/Ethnicity, Customized Hispanic | 4 Participants | 5 Participants | 4 Participants | 14 Participants | 27 Participants |
| Race/Ethnicity, Customized White/Non-Hispanic | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Chile | 4 participants | 5 participants | 4 participants | 14 participants | 27 participants |
| Region of Enrollment United States | 1 participants | 0 participants | 1 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 1 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 4 Participants | 12 Participants | 20 Participants |
| Weight | 8.728 Kilograms STANDARD_DEVIATION 1.392 | 5.516 Kilograms STANDARD_DEVIATION 0.891 | 9.194 Kilograms STANDARD_DEVIATION 3.43 | 7.386 Kilograms STANDARD_DEVIATION 3.218 | 7.599 Kilograms STANDARD_DEVIATION 2.903 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 5 | 5 / 5 | 3 / 5 | 6 / 15 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 1 / 5 | 1 / 15 |
Outcome results
Primary
Number of Subjects Reporting Adverse Events Through 30 Days After Dosing
Safety and tolerability of motavizumab (MEDI-524) was measured by adverse events through 30 days after dosing
Time frame: From the start of treatment to 30 days after dosing
Population: All patients who recieved study drug were included in the analysis of safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524), 3 mg/kg | Number of Subjects Reporting Adverse Events Through 30 Days After Dosing | 3 Participants |
| Motavizumab (MEDI-524), 15 mg/kg | Number of Subjects Reporting Adverse Events Through 30 Days After Dosing | 5 Participants |
| Motavizumab (MEDI-524), 30 mg/kg | Number of Subjects Reporting Adverse Events Through 30 Days After Dosing | 3 Participants |
| Placebo | Number of Subjects Reporting Adverse Events Through 30 Days After Dosing | 6 Participants |
Primary
Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing
Safety and tolerability of motavizumab (MEDI-524) was measured by serious adverse events through 30 days after dosing
Time frame: From the start of treatment to 30 days after dosing
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524), 3 mg/kg | Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing | 0 participants |
| Motavizumab (MEDI-524), 15 mg/kg | Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing | 0 participants |
| Motavizumab (MEDI-524), 30 mg/kg | Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing | 1 participants |
| Placebo | Number of Subjects Reporting Serious Adverse Events Through 30 Days After Dosing | 1 participants |
Primary
The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations
Safety and tolerability of motavizumab (MEDI-524) was measured by the occurrence of increased toxicity grade from baseline as determined by laboratory evaluations (complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and urinalysis) at baseline and at each study collection time point following dosing
Time frame: From the start of treatment to 30 days after dosing
Population: All patients who recieved study drug were included in the analysis of safety.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524), 3 mg/kg | The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations | 0 Participants |
| Motavizumab (MEDI-524), 15 mg/kg | The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations | 1 Participants |
| Motavizumab (MEDI-524), 30 mg/kg | The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations | 1 Participants |
| Placebo | The Occurrence of Increased Toxixity Grade From Baseline as Determined by Laboratory Evaluations | 1 Participants |
Primary
To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30
Mean trough serum concentrations of motavizumab (MEDI-524) were collected on Day 2 and on Day 30. Serum concentrations of MEDI-524 were analysed using a qualified enzyme-linked immunosorbent assay (ELISA).
Time frame: Day 2 and Day 30
Population: All patients who recieved a full dose of study drug were included in the analysis of trough serum concentrations. One patient in the 3 mg/kg group was not assessed for serum trough levels at either Day 2 or Day 30.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Motavizumab (MEDI-524), 3 mg/kg | To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Trough Serum Concentration at Day 30 | 16.63 Micrograms per mililiter | Standard Deviation 13.08 |
| Motavizumab (MEDI-524), 3 mg/kg | To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Trough Serum Concentration at Day 2 | 61.78 Micrograms per mililiter | Standard Deviation 20.09 |
| Motavizumab (MEDI-524), 15 mg/kg | To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Trough Serum Concentration at Day 2 | 170.8 Micrograms per mililiter | Standard Deviation 38.43 |
| Motavizumab (MEDI-524), 15 mg/kg | To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Trough Serum Concentration at Day 30 | 59.18 Micrograms per mililiter | Standard Deviation 12.72 |
| Motavizumab (MEDI-524), 30 mg/kg | To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Trough Serum Concentration at Day 30 | 80.28 Micrograms per mililiter | Standard Deviation 27.34 |
| Motavizumab (MEDI-524), 30 mg/kg | To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Trough Serum Concentration at Day 2 | 333.2 Micrograms per mililiter | Standard Deviation 99.86 |
| Placebo | To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Trough Serum Concentration at Day 30 | 0 Micrograms per mililiter | Standard Deviation 0 |
| Placebo | To Describe the Mean Trough Serum Concentrations of Motavizumab (MEDI-524) Administered as a Single Intravenous Dose at Day 2 and Day 30 | Trough Serum Concentration at Day 2 | 0 Micrograms per mililiter | Standard Deviation 0 |
Secondary
To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0
The serum anti-motavizumab antibody titers were measured in subjects on Day 0 (before dosing). Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay.
Time frame: Immediately before dosing on Day 0
Population: All patients who received a full dose of study drug were included in the analysis of immunogenicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524), 3 mg/kg | To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0 | 0 Participants |
| Motavizumab (MEDI-524), 15 mg/kg | To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0 | 0 Participants |
| Motavizumab (MEDI-524), 30 mg/kg | To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0 | 0 Participants |
| Placebo | To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 0 | 0 Participants |
Secondary
To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30
The serum anti-motavizumab antibody titers were measured in subjects on Day 30. Anti-motavizumab antibody assays were performed at MedImmune using a qualified assay.
Time frame: Day 30
Population: All patients who received a full dose of study drug were included in the analysis of immunogenicity. One patient in the 3 mg/kg group was not assessed for immunogenicity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Motavizumab (MEDI-524), 3 mg/kg | To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30 | 0 Participants |
| Motavizumab (MEDI-524), 15 mg/kg | To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30 | 0 Participants |
| Motavizumab (MEDI-524), 30 mg/kg | To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30 | 0 Participants |
| Placebo | To Describe the Immunogenicity of Motavizumab (MEDI-524) Following a Single IV Dose at Day 30 | 0 Participants |