A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease - Full Text View

Purpose

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.

Condition	Intervention	Phase
Congenital Heart Disease	Biological: Motavizumab Biological: Palivizumab	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of MEDI-524, a Humanized Enhanced Potency Monoclonal Antibody Against Respiratory Syncytial Virus (RSV), in Children With Hemodynamically Significant Congenital Heart Disease

Resource links provided by NLM:

MedlinePlus related topics: Heart Diseases

Drug Information available for: Palivizumab

U.S. FDA Resources

Further study details as provided by MedImmune LLC:

Primary Outcome Measures:

Number of Subjects Reporting Adverse Events Through Study Day 150 [ Time Frame: Days 0-150 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Days 0-150 ] [ Designated as safety issue: Yes ]
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 [ Time Frame: Days 0-150 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The Number of Subjects Hospitalized for RSV Infection. [ Time Frame: Days 0-150 ] [ Designated as safety issue: No ]
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).
The Number of Subjects With RSV Outpatient MA-LRI for Season 2 Only. [ Time Frame: Days 0-150 ] [ Designated as safety issue: No ]
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 [ Time Frame: Days 0-150 ] [ Designated as safety issue: Yes ]
ECLA-based method
Mean Trough Serum Concentration of Motavizumab at Pre-dose 1 [ Time Frame: Pre-dose 1 ] [ Designated as safety issue: No ]
Trough serum concentrations (ug/mL) of motavizumab at pre-dose 1
Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 1 [ Time Frame: 30 days post-dose 1 ] [ Designated as safety issue: No ]
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 [ Time Frame: 30 days post-dose 2 ] [ Designated as safety issue: No ]
Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 2
Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 3 [ Time Frame: 30 days post-dose 3 ] [ Designated as safety issue: No ]
Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 3
Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 4 [ Time Frame: 30 days post-dose 4 ] [ Designated as safety issue: No ]
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 [ Time Frame: Days 0-150 ] [ Designated as safety issue: No ]
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.

Enrollment:	1236
Study Start Date:	October 2005
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Motavizumab Motavizumab was administered as an intramuscular injection at 15 mg/kg every 30 days during the RSV season for a maximum of 5 scheduled doses. 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.	Biological: Motavizumab 15 mg/kg IM administered at monthly intervals Other Name: Medi-524
Active Comparator: Pailvizumab Palivizumab was administered as an intramuscular injection at 15 mg/kg every 30 days during the RSV season for a maximum of 5 scheduled doses. 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.	Biological: Palivizumab 15 mg/kg IM administered at monthly intervals Other Name: Synagis

Arms

Assigned Interventions

Experimental: Motavizumab

Motavizumab was administered as an intramuscular injection at 15 mg/kg every 30 days during the RSV season for a maximum of 5 scheduled doses. 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.

Biological: Motavizumab

15 mg/kg IM administered at monthly intervals

Other Name: Medi-524

Active Comparator: Pailvizumab

Palivizumab was administered as an intramuscular injection at 15 mg/kg every 30 days during the RSV season for a maximum of 5 scheduled doses. 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.

Biological: Palivizumab

15 mg/kg IM administered at monthly intervals

Other Name: Synagis

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.

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 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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538785

Show 153 Study Locations

Sponsors and Collaborators

MedImmune LLC

Investigators

Study Director:

Pamela Griffin, 301-398-0000

MedImmune LLC

More Information

No publications provided

Responsible Party:	Pamela Griffin, Senior Director, Clinical Development, MedImmune, LLC
ClinicalTrials.gov Identifier:	NCT00538785 History of Changes
Obsolete Identifiers:	NCT00240890
Other Study ID Numbers:	MI-CP124-S2
Study First Received:	October 1, 2007
Results First Received:	January 11, 2012
Last Updated:	February 14, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by MedImmune LLC:

Synagis, motavizumab, palivizumab, children, MEDI-524, RSV, congenital hear disease

Additional relevant MeSH terms:

Heart Diseases
Heart Defects, Congenital
Cardiovascular Diseases
Cardiovascular Abnormalities
Congenital Abnormalities

Palivizumab
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 19, 2013