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

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

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.

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Biological: Motavizumab; Biological: Palivizumab

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.

• Study Type: Interventional
• Enrollment (Actual): 1236
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Universitätsklinik für Kinder- und Jugendheilkunde
  • Linz, Austria, 4020
    • Allgemeines Krankenhaus Linz
  • Wein, Austria
    • Universitätsklinik für Kinder- und Jugendheilkunde
• Belgium
  • Antwerpen, Belgium, 2020
    • Ziekenhuisnetwerk Antwerpen - Koningin Paola Kinderziekenhuis
  • Brussel,, Belgium, 1090
    • UZ Brussel
  • Brussells, Belgium, 1090
    • UZ Brussel
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-luc
  • Bruxelles, Belgium, 1020
    • Hôpital Universitaire des Enfants Reine
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Edegem,, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • CHR de la Citadelle
• Bulgaria
  • Pleven, Bulgaria
    • University Multifunctional Hospital for Active Treatment
  • Plovdiv, Bulgaria, 4002
    • University Mulitiprofile Hospital for Active Treatment "St.Georgi"
  • Plovdiv, Bulgaria
    • Multifunctional Hospital for Active Treatment - Pleven
  • Rousse, Bulgaria
    • Regional Dispensary for Pulmonary Diseases with Inpatient sector-Rousse
  • Sofia, Bulgaria
    • Specialized Hospital for Active Treatment of Cardio-vascular Diseases
  • Sofia, Bulgaria
    • Specialized Hospital for Active Treatment of Pediatric Diseases
  • Stara Zagora, Bulgaria
    • University Multifunctional Hospital for Active Treatment
  • Varna, Bulgaria
    • Multifunctional Hospital for Active Treatment - Pleven
• Canada
  • Edmonton, Canada
    • University of Alberta
  • Montreal, Canada
    • Montreal Children's Hospital
  • Montreal, Canada
    • Saint Justine Hospital
  • Ottawa, Canada, K1H 8L1
    • Children's Hospital of Eastern Ontario
  • Saskatoon SK, Canada
    • Saskatchewan Drug Research Institute
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's and Women's Hospital of BC, Room #1R11
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Center
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• Czech Republic
  • Hradec Kralove, Czech Republic, 500 05
    • Fakultni Nemocnice Hradec Kralove
  • Most, Czech Republic, 434 64
    • Nemocnice Most, prispevkova organizace
  • Plzen - Lochotin, Czech Republic, 304 60
    • Fakultni Nemocnice Plzen
  • Praha 2, Czech Republic, 128 51
    • Vseobecna Fakultni Nemocnice V Praze
  • Praha 4, Czech Republic, 147 00
    • Ustav pro peci o matku a dite
  • Praha 5, Czech Republic, 150 06
    • Fakultni nemocnice v Motole
  • Praha 8, Czech Republic, 180 81
    • Fakultni nemocnice Na Bulovce
• Denmark
  • Århus N, Denmark, DK-8200
    • Skejby Sygehus
• France
  • Bordeaux, France, 33076
    • Groupe Hospitalier Pelligrin
  • Dijon, France, 21034
    • CHRU Dijon-Complex du Bocage
  • Le Plessis Robinson, France, 93250
    • Centre chirurgical Marie Lannelongue
  • Marseille, France, 13385
    • Hospital de la Conception
  • Paris, France, 75019
    • Hospital Robert Debre
  • Reims, France, 51092
    • American Memorial Hospital
  • Strasbourg, France, 67098
    • Hospital de Hautepierre
  • Vandoeuvre les Nancy, France, 54511
    • Hospitaux de Brabois
• Germany
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum NRW
  • Freiburg, Germany, 79106
    • Friedrich-Alexander-Universiät Erlangen Nürnberg
  • Hanover, Germany, 36023
    • Medizinische Hochschule Hannover
  • Kiel, Germany, 24105
    • Universitatsklinikum Schleswig Holstein
  • Mainz, Germany, 55105
    • Johannes Gutenberg-Universität
  • München, Germany, 81377
    • LMU Klinikum der Universität
  • Oldenburg, Germany, 26133
    • Klinikum Oldenburg
  • Rostock, Germany, 18055
    • Universitätsklinik Rostock
  • Rostock, Germany, 26133
    • Universitätsklinik Rostock
  • Tübingen, Germany, 72076
    • Universitatsklinikum Tubingen
• Hungary
  • Budapest, Hungary, H-1083
    • Semmelweis Egyetem
  • Budapest, Hungary, H-1096
    • Gottsegen Gyorgy Orszagos Kardiologiai Intezet, Gyermeksziv Kozpont
  • Debrecen, Hungary, H-4012
    • Debreceni Egyetem OEC
  • Gyor, Hungary, 9023
    • Petz Aladar Megyei Korhaz
  • Miskolc, Hungary, H-3526
    • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz
  • Nyiregyhaza, Hungary, H-4400
    • Josa Andras Korhaz
  • Pecs, Hungary, H-7623
    • Pécsi Tudományegyetem
  • Szeged, Hungary, H-6720
    • Szegedi Tudomanyegyetem AOK, Gyermekgyogyaszati Klinika
  • Veszprem, Hungary, H-8200
    • Veszprém Megyei Önkormányzat - Csolnoky Ferenc Kórház
• Israel
  • Beer Sheva, Israel, 84101
    • Soroka University Medical Center
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Holon, Israel, 58100
    • Edith Wolfson Medical Center
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah University Hospital Ein Kerem
  • Petach Tikva, Israel, 49100
    • Schneider Children's Medical Center of Israel
  • Ramat-Gan, Israel, 52621
    • The Chaim Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel-Aviv Sourasky Medical Center
  • Tel Hashomer, Israel, 52621
    • The Chaim Sheba Medical Center
• Lebanon
  • Achrafieh- Beirut, Lebanon
    • St George University Hospital
  • Beirut, Lebanon
    • Hotel Dieu de France
  • Beirut, Lebanon, 113-6044
    • American University of Beirut Medical Center
• Poland
  • Bialystok, Poland, 15-276
    • Samodzielny Publiczny Szpital Akademii Medycznej
  • Bydgoszcz, Poland, 85-168
    • Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Wojewodzki Szpital im. dr Jana Biziela w Bydgoszczy
  • Bydgoszcz, Poland, 85-667
    • Wojewodzki Szpital Dzieciecy W Bydgoszczy
  • Lodz, Poland, 93-338
    • Instytut Centrum Zdrowia Matki Polki
  • Lubin, Poland, 20-093
    • Dzieciecy Szpital Kliniczny im. Prof. Antoniego Gebal Poliklinika
  • Poznan, Poland, 60-535
    • Ginekologiczno-Poloznicy Szpital Kliniczny Uniwersytetu Medycznego w Poznaniu
  • Poznan, Poland, 60-572
    • Szpital Kliniczny Uniwersytetu Medycznego im. Karola Jonschera
  • Szczecin, Poland, 71-252
    • Samodzielny Publiczny Szpital Kliniczny nr 1 im. Tadeusza Sokolowskiego Pomorskiej AM w Szczecinie
  • Warszawa, Poland, 04-736
    • Instytut "Pomnik - Centrum Zdrowia Dziecka"
• Russian Federation
  • Kazan, Russian Federation
    • Kazan State Medical University
  • Krasnodar, Russian Federation, 350086
    • Kuban State Medical Academy
  • Novosibirsk, Russian Federation, 630055
    • Meshalkin Research Institue of Blood circulation
  • St. Petersburg, Russian Federation, 193312
    • City Outpatient Clinic #113
  • St. Petersburg, Russian Federation, 194100
    • Saint Petersburg State Pediatric Medical Academy
  • St. Petersburg, Russian Federation, 198205
    • St. Petersburg City Children's Hospital #1
  • Tomsk, Russian Federation, 634012
    • Research Cardiology Institute of Tomsk Scientific Center
  • Tyumen, Russian Federation, 625000
    • St. Petersburg Pediatric city hospital
• Spain
  • Barakaldo, Spain, 48903
    • Hospital de Cruces
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Córdoba, Spain, 14004
    • Hospital Reina Sofia
  • El Palmar, Spain, 30120
    • Hospital Universitario Virgen de La Arrixaca
  • Esplugas de Llobregat, Spain, 08950
    • Hospital Sant Joan de Déu
  • Girona, Spain, 17007
    • Hospital Josep Trueta
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de Las Nieves
  • Jaen, Spain, 23007
    • Hospital Materno Infantil de Jaén
  • Jerez de la Frontera, Spain, 11407
    • Hospital de Jerez
  • La Coruña, Spain, 15006
    • Hospital Juan Canalejo
  • Madrid, Spain, 28009
    • Hospital Gregorio Marañon
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
  • Madrid, Spain, 28040
    • Hospital La Paz
  • Málaga, Spain, 29011
    • Hospital Materno Infantil
  • San Sebastian, Spain, 20014
    • Hospital Donostia
  • Sevilla, Spain, 41013
    • Hospital Infantil Universitario Virgen del Rocío
  • Vigo, Spain, 36204
    • Hospital Xeral de Vigo
  • Zaragoza, Spain, 5009
    • Hospital Universitario Miguel Servet
• Sweden
  • Göteborg, Sweden, SE-41685
    • Jan Sunnegardh's- Private Practice
  • Lund, Sweden
    • Universitetssjukhuset i Lund
  • Stockholm, Sweden, SE-17176
    • Karolinska University Hospital
  • Uppsala, Sweden, 95 NVB
    • Akademiska Sjukhuset i Uppsala
  • Uppsala, Sweden, 95 NVB
    • Universitetssjukhuset i Lund
• United Kingdom
  • Belfast, United Kingdom, BT 12 6BE
    • Royal Belfast Hospital for Sick Children
  • Bristol, United Kingdom, BS2 8BJ
    • Bristol Royal Hospital for Children
  • Gillingham, United Kingdom, ME7 5NY
    • Medway Maritime Hospital
  • Leeds, United Kingdom, LS1 3EX
    • Leeds General Infirmary
  • Leicester, United Kingdom, LE3 9QP
    • University Hospitals of Leicester NHS Trust
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Pediatric Clinic
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center at Oakland
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
    • San Diego, California, United States, 92123
      • Children's Hospital and Health Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520-8064
      • Yale New Haven Children's Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Orlando, Florida, United States, 32801
      • Nemours Children's Clinic Biomedical Research Department
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • James Whitcomb Riley Hospital For Children
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Children's Hospital Boston
    • Boston, Massachusetts, United States, 02111
      • TUFTS - New England Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • St. Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Stony Brook, New York, United States, 11794
      • Suny At Stony Brook University Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7220
      • Univ. of North Carolina
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Children's Hospital of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Austin, Texas, United States, 78756
      • Children's Cardiology Associates PLLC
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: 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 Names: Synagis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Days 0-150
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.	Days 0-150
Number of Subjects Reporting Laboratory Adverse Events		Days 0-150

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	Days 0-150
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.	Days 0-150
Number of Subjects Who Had Anti-motavizumab Antibodies Detected	ECLA-based method	Days 0-150
Mean Trough Serum Concentration of Motavizumab at Pre-dose 1	Trough serum concentrations (ug/mL) of motavizumab at pre-dose 1	Pre-dose 1
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	30 days post-dose 1
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	30 days post-dose 2
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	30 days post-dose 3
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	30 days post-dose 4
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.	Days 0-150

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Investigators: Study Director: Pamela Griffin, 301-398-0000, MedImmune LLC

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: October 1, 2007
• First Submitted That Met QC Criteria: October 1, 2007
• First Posted (Estimate): October 3, 2007

Study Record Updates

• Last Update Posted (Estimate): February 16, 2012
• Last Update Submitted That Met QC Criteria: February 14, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Synagis, motavizumab, palivizumab, children, MEDI-524, RSV, congenital hear disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital; Anti-Infective Agents; Antiviral Agents; Palivizumab
• Other Study ID Numbers: MI-CP124-S2