Clinical trial NCT00538785: A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Congenital Heart Disease
Keywords: Synagis, motavizumab, palivizumab, children, MEDI-524, RSV, congenital hear disease
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2007-10-03
Enrollment: 1236
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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)

Primary outcomes:
measure: Number of Subjects Reporting Adverse Events Through Study Day 150
timeFrame: Days 0-150
measure: Number of Subjects Reporting Serious Adverse Events Through Study Day 150
timeFrame: Days 0-150
measure: Number of Subjects Reporting Laboratory Adverse Events
timeFrame: Days 0-150
Secondary outcomes:
measure: The Number of Subjects Hospitalized for RSV Infection.
timeFrame: Days 0-150
measure: The Number of Subjects With RSV Outpatient MA-LRI for Season 2 Only.
timeFrame: Days 0-150
measure: Number of Subjects Who Had Anti-motavizumab Antibodies Detected
timeFrame: Days 0-150
measure: Mean Trough Serum Concentration of Motavizumab at Pre-dose 1
timeFrame: Pre-dose 1
measure: Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 1
timeFrame: 30 days post-dose 1
measure: Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 2
timeFrame: 30 days post-dose 2
measure: Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 3
timeFrame: 30 days post-dose 3
measure: Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 4
timeFrame: 30 days post-dose 4
measure: Mean Trough Serum Concentrations of Motavizumab in Subjects Who Underwent Cardiac Surgery With Cardiopulmonary Bypass
timeFrame: Days 0-150
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Pediatric Clinic
state: Arkansas
city: Long Beach
country: United States
facility: Miller Children's Hospital
state: California
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Diego
country: United States
facility: Children's Hospital And Health Center
state: California
city: New Haven
country: United States
facility: Yale New Haven Children's Hospital
state: Connecticut
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Orlando
country: United States
facility: Nemours Children's Clinic Biomedical Research Department
state: Florida
city: Indianapolis
country: United States
facility: James Whitcomb Riley Hospital for Children
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Tufts - New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Stony Brook
country: United States
facility: Suny At Stony Brook University Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ. of North Carolina
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: Children's Hospital of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Austin
country: United States
facility: Children's Cardiology Associates PLLC
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Innsbruck
country: Austria
facility: Universitätsklinik für Kinder- und Jugendheilkunde
city: Linz
country: Austria
facility: Allgemeines Krankenhaus Linz
city: Wein
country: Austria
facility: Universitätsklinik für Kinder- und Jugendheilkunde
city: Antwerpen
country: Belgium
facility: Ziekenhuisnetwerk Antwerpen - Koningin Paola Kinderziekenhuis
city: Brussel,
country: Belgium
facility: UZ Brussel
city: Brussells
country: Belgium
facility: UZ Brussel
city: Bruxelles
country: Belgium
facility: Hôpital Universitaire des Enfants Reine
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem,
country: Belgium
facility: UZ Antwerpen
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: CHR de la Citadelle
city: Pleven
country: Bulgaria
facility: University Multifunctional Hospital for Active Treatment
city: Plovdiv
country: Bulgaria
facility: University Mulitiprofile Hospital for Active Treatment "St.Georgi"
city: Plovdiv
country: Bulgaria
facility: Multifunctional Hospital for Active Treatment - Pleven
city: Rousse
country: Bulgaria
facility: Regional Dispensary for Pulmonary Diseases with Inpatient sector-Rousse
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Cardio-vascular Diseases
city: Sofia
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Pediatric Diseases
city: Stara Zagora
country: Bulgaria
facility: University Multifunctional Hospital for Active Treatment
city: Varna
country: Bulgaria
facility: Multifunctional Hospital for Active Treatment - Pleven
city: Vancouver
country: Canada
facility: Children's and Women's Hospital of BC, Room #1R11
state: British Columbia
city: Halifax
country: Canada
facility: IWK Health Center
state: Nova Scotia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Edmonton
country: Canada
facility: University of Alberta
city: Montreal
country: Canada
facility: Montreal Children's Hospital
city: Montreal
country: Canada
facility: Saint Justine Hospital
city: Ottawa
country: Canada
facility: Children's Hospital Of Eastern Ontario
city: Saskatoon SK
country: Canada
facility: Saskatchewan Drug Research Institute
city: Hradec Kralove
country: Czech Republic
facility: Fakultni nemocnice Hradec Kralove
city: Most
country: Czech Republic
facility: Nemocnice Most, prispevkova organizace
city: Plzen - Lochotin
country: Czech Republic
facility: Fakultni nemocnice Plzen
city: Praha 2
country: Czech Republic
facility: Vseobecna fakultni nemocnice v Praze
city: Praha 4
country: Czech Republic
facility: Ustav pro peci o matku a dite
city: Praha 5
country: Czech Republic
facility: Fakultni nemocnice v Motole
city: Praha 8
country: Czech Republic
facility: Fakultni nemocnice Na Bulovce
city: Århus N
country: Denmark
facility: Skejby Sygehus
city: Bordeaux
country: France
facility: Groupe Hospitalier Pelligrin
city: Dijon
country: France
facility: CHRU Dijon-Complex du Bocage
city: Le Plessis Robinson
country: France
facility: Centre chirurgical Marie Lannelongue
city: Marseille
country: France
facility: Hospital de la Conception
city: Paris
country: France
facility: Hospital Robert Debre
city: Reims
country: France
facility: American Memorial Hospital
city: Strasbourg
country: France
facility: Hospital de Hautepierre
city: Vandoeuvre les Nancy
country: France
facility: Hospitaux de Brabois
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW
city: Freiburg
country: Germany
facility: Friedrich-Alexander-Universiät Erlangen Nürnberg
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig Holstein
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universität
city: München
country: Germany
facility: LMU Klinikum der Universität
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg
city: Rostock
country: Germany
facility: Universitätsklinik Rostock
city: Rostock
country: Germany
facility: Universitätsklinik Rostock
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Gottsegen Gyorgy Orszagos Kardiologiai Intezet, Gyermeksziv Kozpont
city: Debrecen
country: Hungary
facility: Debreceni Egyetem OEC
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Korhaz
city: Miskolc
country: Hungary
facility: Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Korhaz
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem AOK, Gyermekgyogyaszati Klinika
city: Veszprem
country: Hungary
facility: Veszprém Megyei Önkormányzat - Csolnoky Ferenc Kórház
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Achrafieh- Beirut
country: Lebanon
facility: St George University Hospital
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
city: Beirut
country: Lebanon
facility: Hotel Dieu De France
city: Bialystok
country: Poland
facility: Samodzielny Publiczny Szpital Akademii Medycznej
city: Bydgoszcz
country: Poland
facility: Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Wojewodzki Szpital im. dr Jana Biziela w Bydgoszczy
city: Bydgoszcz
country: Poland
facility: Wojewodzki Szpital Dzieciecy W Bydgoszczy
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Lubin
country: Poland
facility: Dzieciecy Szpital Kliniczny im. Prof. Antoniego Gebal Poliklinika
city: Poznan
country: Poland
facility: Ginekologiczno-Poloznicy Szpital Kliniczny Uniwersytetu Medycznego w Poznaniu
city: Poznan
country: Poland
facility: Szpital Kliniczny Uniwersytetu Medycznego im. Karola Jonschera
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 im. Tadeusza Sokolowskiego Pomorskiej AM w Szczecinie
city: Warszawa
country: Poland
facility: Instytut "Pomnik - Centrum Zdrowia Dziecka"
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Krasnodar
country: Russian Federation
facility: Kuban State Medical Academy
city: Novosibirsk
country: Russian Federation
facility: Meshalkin Research Institue of Blood circulation
city: St. Petersburg
country: Russian Federation
facility: City Outpatient Clinic #113
city: St. Petersburg
country: Russian Federation
facility: Saint Petersburg State Pediatric Medical Academy
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg City Children's Hospital #1
city: Tomsk
country: Russian Federation
facility: Research Cardiology Institute of Tomsk Scientific Center
city: Tyumen
country: Russian Federation
facility: St. Petersburg Pediatric city hospital
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Córdoba
country: Spain
facility: Hospital Reina Sofia
city: El Palmar
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Esplugas de Llobregat
country: Spain
facility: Hospital Sant Joan de Deu
city: Girona
country: Spain
facility: Hospital Josep Trueta
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Jaen
country: Spain
facility: Hospital Materno Infantil de Jaen
city: Jerez de la Frontera
country: Spain
facility: Hospital de Jerez
city: La Coruña
country: Spain
facility: Hospital Juan Canalejo
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Materno Infantil
city: San Sebastian
country: Spain
facility: Hospital Donostia
city: Sevilla
country: Spain
facility: Hospital Infantil Universitario Virgen del Rocío
city: Vigo
country: Spain
facility: Hospital Xeral de Vigo
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Göteborg
country: Sweden
facility: Jan Sunnegardh's- Private Practice
city: Lund
country: Sweden
facility: Universitetssjukhuset i Lund
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset i Uppsala
city: Uppsala
country: Sweden
facility: Universitetssjukhuset i Lund
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Gillingham
country: United Kingdom
facility: Medway Maritime Hospital
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: MedImmune LLC
name: Pamela Griffin, 301-398-0000
role: STUDY_DIRECTOR
References: