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

Congenital Heart Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00538785
• Other study ID #: MI-CP124-S2
• Status: Completed
• Phase: Phase 2
• First received: October 1, 2007
• Last updated: February 14, 2012
• Start date: October 2005
• Est. completion date: June 2008

Study information

• Verified date: February 2012
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00240890

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1236
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 24 Months

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases

Intervention

Biological:
• Motavizumab
15 mg/kg IM administered at monthly intervals
• Palivizumab
15 mg/kg IM administered at monthly intervals

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Bulgaria,  Canada,  Czech Republic,  Denmark,  France,  Germany,  Hungary,  Israel,  Lebanon,  Poland,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	Number of Subjects Reporting Laboratory Adverse Events		Days 0-150	Yes
Secondary	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	No
Secondary	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	No
Secondary	Number of Subjects Who Had Anti-motavizumab Antibodies Detected	ECLA-based method	Days 0-150	Yes
Secondary	Mean Trough Serum Concentration of Motavizumab at Pre-dose 1	Trough serum concentrations (ug/mL) of motavizumab at pre-dose 1	Pre-dose 1	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No