MedPath

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

Phase 2
Completed
Conditions
Congenital Heart Disease
Interventions
Biological: Motavizumab
Biological: Palivizumab
Registration Number
NCT00538785
Lead Sponsor
MedImmune LLC
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1236
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MotavizumabMotavizumabMotavizumab 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.
PailvizumabPalivizumabPalivizumab 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.
Primary Outcome Measures
NameTimeMethod
Number of Subjects Reporting Adverse Events Through Study Day 150Days 0-150

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 150Days 0-150

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.

Number of Subjects Reporting Laboratory Adverse EventsDays 0-150
Secondary Outcome Measures
NameTimeMethod
The Number of Subjects Hospitalized for RSV Infection.Days 0-150

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.Days 0-150

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 DetectedDays 0-150

ECLA-based method

Mean Trough Serum Concentration of Motavizumab at Pre-dose 1Pre-dose 1

Trough serum concentrations (ug/mL) of motavizumab at pre-dose 1

Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 130 days post-dose 1

Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 1

Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 230 days post-dose 2

Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 2

Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 330 days post-dose 3

Trough serum concentrations (ug/mL) of motavizumab at 30 days post-dose 3

Mean Trough Serum Concentration of Motavizumab at 30 Days Post-dose 430 days post-dose 4

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 BypassDays 0-150

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.

Trial Locations

Locations (145)

University of Maryland

🇺🇸

Baltimore, Maryland, United States

Johns Hopkins Hospital

🇺🇸

Baltimore, Maryland, United States

Washington University School of Medicine

🇺🇸

St. Louis, Missouri, United States

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Childrens Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Universitätsklinik für Kinder- und Jugendheilkunde

🇦🇹

Wein, Austria

Akron Children's Hospital

🇺🇸

Akron, Ohio, United States

Univ. of North Carolina

🇺🇸

Chapel Hill, North Carolina, United States

Miller Children's Hospital

🇺🇸

Long Beach, California, United States

Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

Nemours Children's Clinic Biomedical Research Department

🇺🇸

Orlando, Florida, United States

University of California Davis Medical Center

🇺🇸

Sacramento, California, United States

UZ Antwerpen

🇧🇪

Edegem, Belgium

Saint Justine Hospital

🇨🇦

Montreal, Canada

University of Alberta

🇨🇦

Edmonton, Canada

Children's Hospital of Michigan

🇺🇸

Detroit, Michigan, United States

Suny At Stony Brook University Medical Center

🇺🇸

Stony Brook, New York, United States

Allgemeines Krankenhaus Linz

🇦🇹

Linz, Austria

CHRU Dijon-Complex du Bocage

🇫🇷

Dijon, France

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

Centre chirurgical Marie Lannelongue

🇫🇷

Le Plessis Robinson, France

University Mulitiprofile Hospital for Active Treatment "St.Georgi"

🇧🇬

Plovdiv, Bulgaria

Specialized Hospital for Active Treatment of Pediatric Diseases

🇧🇬

Sofia, Bulgaria

Nemocnice Most, prispevkova organizace

🇨🇿

Most, Czech Republic

Herz- und Diabeteszentrum NRW

🇩🇪

Bad Oeynhausen, Germany

Johannes Gutenberg-Universität

🇩🇪

Mainz, Germany

Hospital Robert Debre

🇫🇷

Paris, France

Fakultni nemocnice Hradec Kralove

🇨🇿

Hradec Kralove, Czech Republic

Petz Aladar Megyei Korhaz

🇭🇺

Gyor, Hungary

Hospital de la Conception

🇫🇷

Marseille, France

The Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

Hospital de Cruces

🇪🇸

Barakaldo, Spain

Hospital Josep Trueta

🇪🇸

Girona, Spain

Jan Sunnegardh's- Private Practice

🇸🇪

Göteborg, Sweden

Universitetssjukhuset i Lund

🇸🇪

Uppsala, Sweden

Cliniques Universitaires Saint-Luc

🇧🇪

Bruxelles, Belgium

UZ Leuven

🇧🇪

Leuven, Belgium

Groupe Hospitalier Pelligrin

🇫🇷

Bordeaux, France

Montreal Children's Hospital

🇨🇦

Montreal, Canada

Hospital Donostia

🇪🇸

San Sebastian, Spain

Hospital La Paz

🇪🇸

Madrid, Spain

Hospital Reina Sofia

🇪🇸

Córdoba, Spain

Southampton General Hospital

🇬🇧

Southampton, United Kingdom

American Memorial Hospital

🇫🇷

Reims, France

Universitätsklinikum Schleswig Holstein

🇩🇪

Kiel, Germany

Medizinische Hochschule Hannover

🇩🇪

Hanover, Germany

Hospital Vall d'Hebron

🇪🇸

Barcelona, Spain

Karolinska University Hospital

🇸🇪

Stockholm, Sweden

Hospitaux de Brabois

🇫🇷

Vandoeuvre les Nancy, France

Bristol Royal Hospital for Children

🇬🇧

Bristol, United Kingdom

University Hospitals of Leicester NHS Trust

🇬🇧

Leicester, United Kingdom

Friedrich-Alexander-Universiät Erlangen Nürnberg

🇩🇪

Freiburg, Germany

Hospital Universitario Virgen de la Arrixaca

🇪🇸

El Palmar, Spain

Universitätsklinik Rostock

🇩🇪

Rostock, Germany

Josa Andras Korhaz

🇭🇺

Nyiregyhaza, Hungary

Gottsegen Gyorgy Orszagos Kardiologiai Intezet, Gyermeksziv Kozpont

🇭🇺

Budapest, Hungary

Royal Belfast Hospital for Sick Children

🇬🇧

Belfast, United Kingdom

Hospital de Jerez

🇪🇸

Jerez de la Frontera, Spain

Akademiska Sjukhuset i Uppsala

🇸🇪

Uppsala, Sweden

Medway Maritime Hospital

🇬🇧

Gillingham, United Kingdom

Leeds General Infirmary

🇬🇧

Leeds, United Kingdom

Children's Hospital Boston

🇺🇸

Boston, Massachusetts, United States

James Whitcomb Riley Hospital for Children

🇺🇸

Indianapolis, Indiana, United States

Tufts - New England Medical Center

🇺🇸

Boston, Massachusetts, United States

Children's Hospital And Health Center

🇺🇸

San Diego, California, United States

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

Skejby Sygehus

🇩🇰

Århus N, Denmark

Hospital de Hautepierre

🇫🇷

Strasbourg, France

Saskatchewan Drug Research Institute

🇨🇦

Saskatoon SK, Canada

Klinikum Oldenburg

🇩🇪

Oldenburg, Germany

Hospital Materno Infantil de Jaen

🇪🇸

Jaen, Spain

Hospital Juan Canalejo

🇪🇸

La Coruña, Spain

Hospital 12 de Octubre

🇪🇸

Madrid, Spain

University of Rochester

🇺🇸

Rochester, New York, United States

Children's Cardiology Associates PLLC

🇺🇸

Austin, Texas, United States

Children's Hospital of Oklahoma

🇺🇸

Oklahoma City, Oklahoma, United States

Hospital Universitario Virgen de Las Nieves

🇪🇸

Granada, Spain

University of Virginia

🇺🇸

Charlottesville, Virginia, United States

Hospital Infantil Universitario Virgen del Rocío

🇪🇸

Sevilla, Spain

Hospital Materno Infantil

🇪🇸

Málaga, Spain

Hospital Xeral de Vigo

🇪🇸

Vigo, Spain

Memorial Hospital of South Bend

🇺🇸

South Bend, Indiana, United States

Children's Hospital and Research Center at Oakland

🇺🇸

Oakland, California, United States

Regional Dispensary for Pulmonary Diseases with Inpatient sector-Rousse

🇧🇬

Rousse, Bulgaria

Children's and Women's Hospital of BC, Room #1R11

🇨🇦

Vancouver, British Columbia, Canada

Children's Hospital Of Eastern Ontario

🇨🇦

Ottawa, Canada

Fakultni nemocnice v Motole

🇨🇿

Praha 5, Czech Republic

LMU Klinikum der Universität

🇩🇪

München, Germany

Universitätsklinikum Tübingen

🇩🇪

Tübingen, Germany

Pecsi Tudomanyegyetem

🇭🇺

Pecs, Hungary

Schneider Children's Medical Center of Israel

🇮🇱

Petach Tikva, Israel

Shaare Zedek Medical Center

🇮🇱

Jerusalem, Israel

Szegedi Tudomanyegyetem AOK, Gyermekgyogyaszati Klinika

🇭🇺

Szeged, Hungary

Veszprém Megyei Önkormányzat - Csolnoky Ferenc Kórház

🇭🇺

Veszprem, Hungary

St George University Hospital

🇱🇧

Achrafieh- Beirut, Lebanon

Kazan State Medical University

🇷🇺

Kazan, Russian Federation

Hospital Sant Joan de Deu

🇪🇸

Esplugas de Llobregat, Spain

Hospital Gregorio Marañon

🇪🇸

Madrid, Spain

Hospital Universitario Miguel Servet

🇪🇸

Zaragoza, Spain

Hotel Dieu De France

🇱🇧

Beirut, Lebanon

CHR de la Citadelle

🇧🇪

Liège, Belgium

Fakultni nemocnice Na Bulovce

🇨🇿

Praha 8, Czech Republic

Rambam Medical Center

🇮🇱

Haifa, Israel

Tel-Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

Ziekenhuisnetwerk Antwerpen - Koningin Paola Kinderziekenhuis

🇧🇪

Antwerpen, Belgium

UZ Gent

🇧🇪

Gent, Belgium

The Chaim Sheba Medical Center

🇮🇱

Tel Hashomer, Israel

American University of Beirut Medical Center

🇱🇧

Beirut, Lebanon

Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Wojewodzki Szpital im. dr Jana Biziela w Bydgoszczy

🇵🇱

Bydgoszcz, Poland

Wojewodzki Szpital Dzieciecy W Bydgoszczy

🇵🇱

Bydgoszcz, Poland

Ginekologiczno-Poloznicy Szpital Kliniczny Uniwersytetu Medycznego w Poznaniu

🇵🇱

Poznan, Poland

Research Cardiology Institute of Tomsk Scientific Center

🇷🇺

Tomsk, Russian Federation

Tulane University Health Sciences Center

🇺🇸

New Orleans, Louisiana, United States

UZ Brussel

🇧🇪

Brussells, Belgium

Specialized Hospital for Active Treatment of Cardio-vascular Diseases

🇧🇬

Sofia, Bulgaria

Fakultni nemocnice Plzen

🇨🇿

Plzen - Lochotin, Czech Republic

Debreceni Egyetem OEC

🇭🇺

Debrecen, Hungary

Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház

🇭🇺

Miskolc, Hungary

Hadassah University Hospital Ein Kerem

🇮🇱

Jerusalem, Israel

Samodzielny Publiczny Szpital Akademii Medycznej

🇵🇱

Bialystok, Poland

Kuban State Medical Academy

🇷🇺

Krasnodar, Russian Federation

Meshalkin Research Institue of Blood circulation

🇷🇺

Novosibirsk, Russian Federation

Saint Petersburg State Pediatric Medical Academy

🇷🇺

St. Petersburg, Russian Federation

Arkansas Pediatric Clinic

🇺🇸

Little Rock, Arkansas, United States

Ustav pro peci o matku a dite

🇨🇿

Praha 4, Czech Republic

Szpital Kliniczny Uniwersytetu Medycznego im. Karola Jonschera

🇵🇱

Poznan, Poland

Multifunctional Hospital for Active Treatment - Pleven

🇧🇬

Varna, Bulgaria

Yale New Haven Children's Hospital

🇺🇸

New Haven, Connecticut, United States

Semmelweis Egyetem

🇭🇺

Budapest, Hungary

Hôpital Universitaire des Enfants Reine

🇧🇪

Bruxelles, Belgium

University Multifunctional Hospital for Active Treatment

🇧🇬

Stara Zagora, Bulgaria

Vseobecna fakultni nemocnice v Praze

🇨🇿

Praha 2, Czech Republic

Soroka University Medical Center

🇮🇱

Beer Sheva, Israel

Edith Wolfson Medical Center

🇮🇱

Holon, Israel

Instytut Centrum Zdrowia Matki Polki

🇵🇱

Lodz, Poland

Samodzielny Publiczny Szpital Kliniczny nr 1 im. Tadeusza Sokolowskiego Pomorskiej AM w Szczecinie

🇵🇱

Szczecin, Poland

St. Petersburg City Children's Hospital #1

🇷🇺

St. Petersburg, Russian Federation

IWK Health Center

🇨🇦

Halifax, Nova Scotia, Canada

Dzieciecy Szpital Kliniczny im. Prof. Antoniego Gebal Poliklinika

🇵🇱

Lubin, Poland

Instytut "Pomnik - Centrum Zdrowia Dziecka"

🇵🇱

Warszawa, Poland

City Outpatient Clinic #113

🇷🇺

St. Petersburg, Russian Federation

St. Petersburg Pediatric city hospital

🇷🇺

Tyumen, Russian Federation

Royal Brompton Hospital

🇬🇧

London, United Kingdom

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

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