Study of MEDI-524 (Motavizumab) for the Prophylaxis of Serious Respiratory Syncytial Virus (RSV) Disease in High-Risk Children

A Pivotal Phase 3 Study of MEDI-524 (Numax; Motavizumab), an Enhanced Potency Humanized RSV Monoclonal Antibody, for the Prophylaxis of Serious RSV Disease in High-Risk Children

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00129766

Enrollment

6635

Registered

2005-08-12

Start date

2004-11-30

Completion date

2006-05-31

Last updated

2013-08-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Respiratory Syncytial Virus Infections

Keywords

Respiratory Syncytial Virus (RSV), motavizumab, palivizumab, Synagis

Brief summary

The primary objective of this study was to compare the safety and efficacy of motavizumab to palivizumab when administered monthly by intramuscular (IM) injection for the reduction of the incidence of RSV hospitalization among children at high risk for serious RSV disease. A secondary objective was to compare the incidence of medically-attended lower respiratory infections (LRIs) between treatment groups.

Detailed description

A randomized, double-blind, palivizumab-controlled, multi-center, multi-national trial conducted during 2 Northern Hemisphere RSV seasons with an intervening season in the Southern Hemisphere. Each child only participated during a single RSV season. Approximately 6,600 children at risk for serious RSV disease were to be randomized in a 1:1 ratio to receive either 15 mg/kg of palivizumab or motavizumab by IM injection every 30 days for a total of 5 doses.

Interventions

BIOLOGICALmotavizumab (MEDI-524)

Motavizumab, 15 mg/kg administered intramuscularly for 5 monthly doses

BIOLOGICALpalivizumab

Palivizumab, 15 mg/kg administered intramuscularly for 5 monthly doses

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

Inclusion criteria

* 24 months of age or younger at randomization (child must be randomized on or before his/her 24-month birthday) with a diagnosis of chronic lung disease (CLD) of prematurity requiring medical intervention/management (i.e., supplemental oxygen, bronchodilators, or diuretics) within 6 months before randomization OR: * 35 weeks gestational age or less at birth and 6 months of age or younger at randomization (children were to be randomized on or before his/her 6-month birthday)

Exclusion criteria

* Hospitalization at the time of randomization (unless discharge was anticipated within 10 days) * Mechanical ventilation or other mechanical support (including continuous positive airways pressure \[CPAP\]) * Life expectancy \< 6 months * Active RSV infection (a child with signs/symptoms of respiratory infection must have had negative RSV testing) * Known renal impairment * Known hepatic dysfunction * Chronic seizure or evolving or unstable neurologic disorder * Congenital heart disease \[CHD\] (children with uncomplicated CHD \[e.g., patent ductus arterious (PDA), small septal defect\] and children with complicated CHD that were currently anatomically and hemodynamically normal could be enrolled) * Known immunodeficiency * Mother with HIV infection (unless the child has been proven to be not infected) * Known allergy to Ig products * Receipt of palivizumab, RSV-IGIV, or other RSV-specific monoclonal antibody, or any other polyclonal antibody (for example, hepatitis B IG, IVIG, VZIG) within 3 months prior to randomization * Anticipated use of palivizumab or IVIG during the study (blood transfusions permitted) * Previous receipt of RSV vaccines * Participation in other investigational drug product studies

Design outcomes

Primary

Measure	Time frame	Description
Incidence of RSV Hospitalization (Includes Deaths by RSV)	Days 0 - 150	RSV hospitalization was defined as 1) a respiratory hospitalization with a positive RSV test (primary), 2) a new onset of lower respiratory symptoms in an already hospitalized child, with an objective measure of worsening respiratory status and positive RSV test (nosocomial), or 3) death demonstrated to have been caused by RSV (by autopsy or clinical history and virologic evidence).
Number of Participants Reporting Any Adverse Events (AEs)	Days 0 - 150	Number of participants reporting one or more AEs
Number of Participants Reporting Any Related AEs	Days 0 - 150	Number of participants reporting one or more AEs considered related to study drug by the investigator
Number of Participants Reporting Any Serious Adverse Events (SAEs)	Days 0 - 150	Number of participants reporting one or more SAEs
Number of Participants Reporting Any Related SAEs	Days 0 - 150	Number of participants reporting one or more SAEs considered related to study drug by the investigator
Number of Participants Reporting AEs by Highest Severity Grade	Days 0 - 150	Adverse events events were graded by severity; Level 1, 2, 3, or 4
Number of Participants Who Discontinued Study Drug Due to AEs	Days 0 - 150	—
Number of Participants Who Died	Days 0 - 150	—
Number of Participants Reporting Changes in Vital Signs From Baseline	Days 0 - 150	Vital signs that were in a higher toxicity grade than observed at baseline were to be recorded as AEs

Secondary

Measure	Time frame	Description
The Frequency of Prescribed Antibiotics for Medically-attended OM Infections	Days 0 - 150	The average number of presciptions per event per subject was summarized for each treatment group.
The Serum Concentrations of Motavizumab at Day 0	Day 0	Mean serum concentrations of motavizumab at Day 0
The Number of Participants With Anti-motavizumab Antibodies	Day 0 - 120	Detection of anti-motavizumab antibodies was defined as a titer with a dilution value equal to or greater than 1:10.
The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 1	30 days post Dose 1	Mean serum concentrations of motavizumab at 30 days post Dose 1
The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 2	30 days post Dose 2	Mean serum concentrations of motavizumab at 30 days post Dose 2
The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 3	30 days post Dose 3	Mean serum concentrations of motavizumab at 30 days post Dose 3
The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 4	30 days post Dose 4	Mean serum concentrations of motavizumab at 30 days post Dose 4
The Incidence of Outpatient Medically-attended Lower Respiratory Illness (LRI)	Day 0 - 150	LRI was defined as an event of bronchiolitis or pneumonia or the occurance of a lower tract infectious illness as determined by the PI based on medical history, signs, and symptoms.
The Incidence of RSV-specific Medically-attended Outpatient Lower Respiratory Illnesses (LRIs) Between Treatment Groups	Days 0 - 150	The RSV-specific LRI was defined as an outpatient medically-attended LRI associated with a positive RSV test and was not inclusive of events that required hospitalization.
The Incidence of Medically-attended Otitis Media (OM) Infections	Days 0 - 150	Otitis media (OM) was to be recorded as the diagnosis if the following terms were used by the medical care provider: acute OM, acute tympanic membrane (TM) perforation, bulging TM, red TM with fever, OM with effusion, or middle ear effusion. A new episode was defined as a physician-diagnosed OM in either ear after a normal middle ear exam of the ear in question or an episode of acute OM greater than or equal to 21 days after resolution of the previous episode. A diagnosis of persistent middle ear effusion was not to be recorded as a new OM event.
The Frequency of Prescribed Antibiotics for Medically-attended LRI	Days 0 - 150	The average number of presciptions per event per subject was summarized for each treatment group.

Countries

Argentina, Australia, Austria, Brazil, Bulgaria, Canada, Chile, Czechia, Denmark, France, Germany, Greece, Hungary, Iceland, Israel, Italy, New Zealand, Poland, Russia, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States

Participant flow

Recruitment details

A total of 6,635 children were randomized in a 1:1 ratio at 347 centers in 24 countries within the Northern and Southern hemispheres between 01/Nov/2004 and 09/Dec/2005; each child participated in the study for a single RSV season.

Pre-assignment details

Randomization was blocked by study site and stratified according to presence/absence of CLD of prematurity requiring medical intervention/management.

Participants by arm

Arm	Count
Palivizumab Palivizumab, 15 mg/kg administered intramuscularly for 5 monthly doses	3,306
Motavizumab Motavizumab, 15 mg/kg administered intramuscularly for 5 monthly doses	3,329
Total	6,635

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	3	8
Overall Study	Lost to Follow-up	26	21
Overall Study	Withdrawal of consent	31	30

Baseline characteristics

Characteristic	Palivizumab	Motavizumab	Total
Age Continuous	3.98 months STANDARD_DEVIATION 3.78	3.99 months STANDARD_DEVIATION 3.75	3.99 months STANDARD_DEVIATION 3.76
Region of Enrollment Argentina	38 participants	34 participants	72 participants
Region of Enrollment Australia	85 participants	81 participants	166 participants
Region of Enrollment Austria	35 participants	34 participants	69 participants
Region of Enrollment Brazil	69 participants	66 participants	135 participants
Region of Enrollment Bulgaria	95 participants	101 participants	196 participants
Region of Enrollment Canada	134 participants	132 participants	266 participants
Region of Enrollment Chile	93 participants	87 participants	180 participants
Region of Enrollment Czech Republic	171 participants	177 participants	348 participants
Region of Enrollment Denmark	30 participants	27 participants	57 participants
Region of Enrollment France	107 participants	111 participants	218 participants
Region of Enrollment Germany	131 participants	122 participants	253 participants
Region of Enrollment Greece	32 participants	34 participants	66 participants
Region of Enrollment Hungary	198 participants	192 participants	390 participants
Region of Enrollment Iceland	20 participants	19 participants	39 participants
Region of Enrollment Israel	301 participants	305 participants	606 participants
Region of Enrollment Italy	93 participants	96 participants	189 participants
Region of Enrollment New Zealand	26 participants	26 participants	52 participants
Region of Enrollment Poland	106 participants	105 participants	211 participants
Region of Enrollment Russian Federation	42 participants	45 participants	87 participants
Region of Enrollment Spain	191 participants	181 participants	372 participants
Region of Enrollment Sweden	54 participants	55 participants	109 participants
Region of Enrollment Turkey	36 participants	42 participants	78 participants
Region of Enrollment United Kingdom	89 participants	90 participants	179 participants
Region of Enrollment United States	1130 participants	1167 participants	2297 participants
Sex: Female, Male Female	1495 Participants	1513 Participants	3008 Participants
Sex: Female, Male Male	1811 Participants	1816 Participants	3627 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	2,777 / 3,298	2,784 / 3,315
serious Total, serious adverse events	506 / 3,298	485 / 3,315

Outcome results

Primary

Incidence of RSV Hospitalization (Includes Deaths by RSV)

RSV hospitalization was defined as 1) a respiratory hospitalization with a positive RSV test (primary), 2) a new onset of lower respiratory symptoms in an already hospitalized child, with an objective measure of worsening respiratory status and positive RSV test (nosocomial), or 3) death demonstrated to have been caused by RSV (by autopsy or clinical history and virologic evidence).

Time frame: Days 0 - 150

Population: The Intent-to-Treat (ITT) Population included all patients randomized into the study.

Arm	Measure	Value (NUMBER)
Palivizumab	Incidence of RSV Hospitalization (Includes Deaths by RSV)	62 Participants
Motavizumab	Incidence of RSV Hospitalization (Includes Deaths by RSV)	46 Participants

Comparison: ITT population95% CI: [0.503, 1.083]t-test, 2 sided

Primary