Survey of Inhibitors in Plasma-Product Exposed Toddlers - Full Text View

Purpose

The primary objective of the study is to assess the immunogenicity of VWF/FVIII and of rFVIII concentrates by determining the frequency of inhibitor development in previously untreated patients (PUPs) or minimally blood component-treated (MBCTPs) in the first 50 EDs or in the first 3 years from enrollment, whichever occurs first.

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Condition	Intervention	Phase
Hemophilia A	Drug: PLASMA DERIVED Factor VIII Drug: Recombinant FVIII	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	Inhibitor Development in Previously Untreated Patients (PUPs) or Minimally Blood Component-Treated Patients (MBCTPs) When Exposed to Plasma-derived Von Willebrand Factor-Containing Factor VIII (VWF/FVIII) Concentrates and to Recombinant Factor VIII (rFVIII) Concentrates: An Independent, International, Multicentre, Prospective, Controlled, Randomised, Open Label, Clinical Trial

Resource links provided by NLM:

Genetics Home Reference related topics: hemophilia

MedlinePlus related topics: Hemophilia

Drug Information available for: Kogenate Moroctocog Alfa Advate

U.S. FDA Resources

Further study details as provided by Fondazione Angelo Bianchi Bonomi:

Primary Outcome Measures:

Frequency of FVIII inhibitor formation in patients treated with plasma-derived vWF/FVIII compared to patients treated with recombinant FVIII [ Time Frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To evaluate the frequency of transient inhibitors [ Time Frame: in the 6 months after inhibitor development or untill the immunosoppresive treatment ] [ Designated as safety issue: Yes ]
To evaluate the modality of occurrence of inhibitors (number of EDs, titre at onset, etc) [ Time Frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first ] [ Designated as safety issue: No ]
Evaluate clinical factors potentially associated to inhibitor development(age at first treatment, severity of bleeding,surgery,intensity of treatment,time of treatment in relation to vaccinations,concurrent disease) [ Time Frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first ] [ Designated as safety issue: No ]
To evaluate the incidence of all other adverse events related and not related to the products used [ Time Frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	300
Study Start Date:	November 2009
Estimated Study Completion Date:	November 2014
Estimated Primary Completion Date:	November 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: pd vWF/FVIII Plasma-derived vWF/FVIII	Drug: PLASMA DERIVED Factor VIII Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding Other Name: ALPHANATE
Active Comparator: rFVIII Recombinant FVIII	Drug: Recombinant FVIII Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding Other Name: ADVATE

Detailed Description:

Patients meeting the enrollment criteria will be consecutively enrolled at each participating centre, randomized to be treated exclusively with a single FVIII product either plasma-derived or recombinant, and followed up until inhibitor development or until 50 exposure days (EDs) or 3 years from enrolment have elapsed, whichever comes first. Study products, belonging to the class of rFVIII concentrates and to the class of plasma-derived VWF/FVIII concentrates, will be provided for free to the patients for all the duration of the study

Eligibility

Ages Eligible for Study:	up to 6 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male subjects
Any ethnicity
Age <6 years
Severe haemophilia A (FVIII:C <1%), as confirmed at enrolment by the central laboratory.

o Those patients diagnosed locally as severe but subsequently found to have FVIII levels >= 1% on testing at the central laboratory will be separately recorded in the screening list.
Previously untreated (0 EDs to any FVIII concentrates or blood products) or minimally treated (<5 EDs) with blood components, namely whole blood, fresh frozen plasma, packed red blood cells, platelets or cryoprecipitate.

o Patients not meeting these criteria will be separately recorded in the screening list.
Negative inhibitor measurement at both local and central laboratory at screening
Ability to comply with study requirements
Signed informed consent of legal tutors o Patients who will not accept to enter into the study or to be randomized will be separately recorded.

Exclusion Criteria:

Previous history of FVIII inhibitor
Other congenital or acquired bleeding defects
Plasma FVIII level >= 1%, as assayed at the central laboratory

o Those patients originally diagnosed locally as severe but subsequently found to have FVIII levels ranging from 1% to 2% on testing at the central laboratory will be separately recorded in the screening list.
Concomitant congenital or acquired immunodeficiency
Concomitant treatment with systemic immunosuppressive drugs
Concomitant treatment with any investigational drug

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01064284

Contacts

Contact: Luca Curtarelli, Ph.D.	+39 02 566651	l.curtarelli@sintesiresearch.com
Contact: William Harel, Ph.D.	+1 818 507 7846	w.harel@sintesiresearch.com

Locations

United States, California
City of Hope Medical Center	Recruiting
Duarte, California, United States, 91010
Principal Investigator: Nadia Ewing, MD
Childrens Hospital Los Angeles	Recruiting
Los Angeles, California, United States, 90027
Principal Investigator: Guy Young, MD
Childrens Hospital of Orange County	Recruiting
Orange, California, United States, 92868
Principal Investigator: Amit Soni, MD
Sub-Investigator: Diane Nugent, MD
United States, Colorado
Mountain States Regional Hemophilia and Thrombosis Center	Not yet recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Marilyn Manco-Johnson, MD
United States, Illinois
RUSH University Medical Center	Recruiting
Chicago, Illinois, United States, 60612
Principal Investigator: Leonard A. Valentino, MD
University of Illinois College of Medicine	Not yet recruiting
Peoria, Illinois, United States, 61614
Principal Investigator: Michael Tarantino, MD
United States, Louisiana
Tulane University School of Medicine, Section of Hematology/Oncology	Recruiting
New Orleans, Louisiana, United States, 70112
Principal Investigator: Rebecca Kruse-Jarres, MD, MPH
United States, Michigan
MSU Center for Bleeding and Clotting Disorders	Not yet recruiting
East Lansing, Michigan, United States, 48824
Principal Investigator: Roshni Kulkarni, MD
United States, Mississippi
Univ of Mississippi Medical Center, Pediatric Hematology/Oncology	Not yet recruiting
Jackson, Mississippi, United States, 39216
Principal Investigator: Suvankar Majumdar, MD
United States, Missouri
Children's Mercy Hospital, Kansas City Regional Hemophilia Center	Recruiting
Kansas City, Missouri, United States, 64108
Principal Investigator: Brian M. Wicklund, MDCM, MPH, FAAP
United States, Nevada
Hemophilia Treatment Center of Las Vegas	Recruiting
Las Vegas, Nevada, United States, 89109
Principal Investigator: Jonathan Bernstein, MD
United States, New Mexico
University of New Mexico, Dept. of Pediatrics	Recruiting
Albuquerque, New Mexico, United States, 87131
Principal Investigator: James V. Mckinnell, MD
United States, North Dakota
Sanford Health Hospital, Pediatric Hematology/Oncology Dept.	Recruiting
Fargo, North Dakota, United States, 58102
Principal Investigator: Nathan L. Kobrinsky, MD
United States, Pennsylvania
The Childrens Hospital of Philadelphia	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Leslie Raffini, MD
United States, Texas
Children's Medical Center, Center for Cancer and Blood Disorders	Recruiting
Dallas, Texas, United States, 75235
Principal Investigator: George R. Buchanan, MD
Cook Children's Medical Center	Recruiting
Forth Worth, Texas, United States, 76104
Principal Investigator: Donald Beam, MD

Sponsors and Collaborators

Fondazione Angelo Bianchi Bonomi

Investigators

Principal Investigator:

Pier M. Mannucci, Professor

University of Milan, Milan, Italy

More Information

No publications provided

Responsible Party:	Prof. Pier Mannuccio Mannucci, University of Milan, Italy
ClinicalTrials.gov Identifier:	NCT01064284 History of Changes
Other Study ID Numbers:	ABB - 09 - 001, 2009-011186-88
Study First Received:	February 4, 2010
Last Updated:	August 19, 2011
Health Authority:	Austria : Federal Ministry for Labour, Health, and Social Affairs Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment Brazil: National Health Surveillance Agency Chile: Instituto de Salud Publica de Chile Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos Czech Republic: State Institute for Drug Control Egypt: Ministry of Health and Population France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) France: French Data Protection Authority Germany: Federal Institute for Drugs and Medical Devices India: Drugs Controller General of India Iran: Ministry of Health Italy: The Italian Medicines Agency Mexico: Federal Commission for Sanitary Risks Protection Poland: Ministry of Health Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Portugal: National Pharmacy and Medicines Institute Romania: National Medicines Agency Saudi Arabia: King Faisal Hospital Ethics Committee Slovakia: State Institute for Drug Control South Africa: Medicines Control Council Spain: Spanish Agency of Medicines Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Institutional Review Board

Keywords provided by Fondazione Angelo Bianchi Bonomi:

Hemophilia A
Factor VIII inhibitors
vWF/FVIII
rFVIII

Additional relevant MeSH terms:

Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders

Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013

Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET)