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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00129766
First received: August 10, 2005
Last updated: June 21, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Respiratory Syncytial Virus Infections
Biological: motavizumab (MEDI-524)
Biological: palivizumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Incidence of RSV Hospitalization (Includes Deaths by RSV) [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: Yes ]
    Number of participants reporting one or more AEs

  • Number of Participants Reporting Any Related AEs [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: Yes ]
    Number of participants reporting one or more SAEs

  • Number of Participants Reporting Any Related SAEs [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: Yes ]
    Adverse events events were graded by severity; Level 1, 2, 3, or 4

  • Number of Participants Who Discontinued Study Drug Due to AEs [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: Yes ]
  • Number of Participants Who Died [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: Yes ]
  • Number of Participants Reporting Changes in Vital Signs From Baseline [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: Yes ]
    Vital signs that were in a higher toxicity grade than observed at baseline were to be recorded as AEs


Secondary Outcome Measures:
  • The Incidence of Outpatient Medically-attended Lower Respiratory Illness (LRI) [ Time Frame: Day 0 - 150 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: No ]
    The average number of presciptions per event per subject was summarized for each treatment group.

  • The Frequency of Prescribed Antibiotics for Medically-attended OM Infections [ Time Frame: Days 0 - 150 ] [ Designated as safety issue: No ]
    The average number of presciptions per event per subject was summarized for each treatment group.

  • The Number of Participants With Anti-motavizumab Antibodies [ Time Frame: Day 0 - 120 ] [ Designated as safety issue: No ]
    Detection of anti-motavizumab antibodies was defined as a titer with a dilution value equal to or greater than 1:10.

  • The Serum Concentrations of Motavizumab at Day 0 [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
    Mean serum concentrations of motavizumab at Day 0

  • The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 1 [ Time Frame: 30 days post Dose 1 ] [ Designated as safety issue: No ]
    Mean serum concentrations of motavizumab at 30 days post Dose 1

  • The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 2 [ Time Frame: 30 days post Dose 2 ] [ Designated as safety issue: No ]
    Mean serum concentrations of motavizumab at 30 days post Dose 2

  • The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 3 [ Time Frame: 30 days post Dose 3 ] [ Designated as safety issue: No ]
    Mean serum concentrations of motavizumab at 30 days post Dose 3

  • The Trough Serum Concentrations of Motavizumab at 30 Days Post Dose 4 [ Time Frame: 30 days post Dose 4 ] [ Designated as safety issue: No ]
    Mean serum concentrations of motavizumab at 30 days post Dose 4


Enrollment: 6635
Study Start Date: November 2004
Study Completion Date: May 2006
Primary Completion Date: May 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: palivizumab
15 mg/kg administered intramuscularly for 5 monthly doses
Biological: palivizumab
Palivizumab, 15 mg/kg administered intramuscularly for 5 monthly doses
Other Name: Synagis
Experimental: motavizumab (MEDI-524)
15 mg/kg of motavizumab was administered intramuscularly for 5 monthly doses
Biological: motavizumab (MEDI-524)
Motavizumab, 15 mg/kg administered intramuscularly for 5 monthly doses
Other Name: MEDI-524

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.

  Eligibility

Ages Eligible for Study:   up to 24 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00129766

  Show 344 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: M Pamela Griffin, MD MedImmune LLC
  More Information

Publications:
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00129766     History of Changes
Other Study ID Numbers: MI-CP110
Study First Received: August 10, 2005
Results First Received: June 21, 2013
Last Updated: June 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Respiratory Syncytial Virus (RSV)
motavizumab
palivizumab
Synagis

Additional relevant MeSH terms:
Respiratory Syncytial Virus Infections
Virus Diseases
Pneumovirus Infections
Paramyxoviridae Infections
Mononegavirales Infections
RNA Virus Infections
Antibodies, Monoclonal
Palivizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014