Survey of Inhibitors in Plasma-Product Exposed Toddlers

Phase 4

Completed

• Conditions: Hemophilia A
• Interventions: Drug: Recombinant FVIII; Drug: PLASMA DERIVED Factor VIII

• Registration Number: NCT01064284
• Lead Sponsor: Fondazione Angelo Bianchi Bonomi

Brief Summary

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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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

Study Timeline

• Study Start: 2010-01
• Study First Submitted: 2010-02-04
• Study First Submitted QC: 2010-02-05
• Study First Posted: 2010-02-08
• Primary Completion: 2015-05
• Study Completion: 2015-05
• Results First Submitted: 2016-12-02
• Results First Submitted QC: 2017-02-23
• Results First Posted: 2017-04-07
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-26
• Last Update Posted: 2017-08-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 303

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rFVIII	Recombinant FVIII	Recombinant FVIII
PLASMA DERIVED Factor VIII	PLASMA DERIVED Factor VIII	Plasma-derived vWF/FVIII

Primary Outcome Measures

Name	Time	Method
To Assess the Immunogenicity of Plasma Derived VWF/FVIII and rFVIII Concentrates by Determining the Frequency of Inhibitor Development in the First 50 EDs or in the First 3 Years From Enrolment, Whichever Comes First in PUPs and MBCTs	During the first 50 exposure days or first 3 years of enrollment, whichever occurs first	Expressed with the numebr of patients for each group who developed FVIII inhibitors.; PUPs: Previously Untreated Patients MBCTPs: Minimally Blood Component-Treated Patients

Secondary Outcome Measures

Name	Time	Method
To Evaluate the Anamnestic Response of Inhibitor Patients	During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Frequency of Transient Inhibitors	In the 6 months after inhibitor development	Number of participants for each group who developed transient inhibitors (this means, those inhibitors which disappeared spontaneously within 6 months without immunotolerance treatment).
To Evaluate the Modality of Occurrence of Inhibitors (Titre at Onset)	During 6 months of observation, from the inhibitor occurrence	Inhibitor Titre at Onset
To Evaluate the Modality of Occurrence of Inhibitors (Number of EDs)	During the first 50 exposure days or first 3 years of enrollment, whichever occurs first	Number of EDs: Number of Exposure Days (EDs) after which the inhibitors develop
To Evaluate Clinical Factors Potentially Associated to Inhibitor Development	During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate Laboratory Factors Potentially Associated to Inhibitor Development	During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Incidence of All Other Adverse Events Related and Not Related to the Products Used	During the first 50 exposure days or first 3 years of enrollment, whichever occurs first

Trial Locations

Locations (48)

Fundacion de la Hemofilia; 🇦🇷 Buenos Aires, Argentina

Centro de Pesquisa Clinica HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti; 🇧🇷 Rio de Janeiro, Brazil

Hemophilia Treatment Center of Las Vegas; 🇺🇸 Las Vegas, Nevada, United States

Centro de Hemofilicos del Hospital de Niños Roberto del Rio Instituto de Investigaciones Hematologicas; 🇨🇱 Santiago, Chile

Lokmanya TilakMunicipal Medical College &General Hospital - Sion; 🇮🇳 Mumbai, India

Unidad Medica de Alta Especialidad (UMAE), Hospital de Pediatria. Centro Medico Nacional de Occidente Istituto Mexicano del Seguro Social; 🇲🇽 Jalisco, Mexico

Faculty of Medicine Ain Shams University Department Pediatrics; 🇪🇬 Cairo, Egypt

Karnataka Hemophilia Care and Hematology Research Center; 🇮🇳 Karnataka, India

Hemophilia Center - Hematoogy & Oncology Dept. Shiraz University of Medical Science Ayatollah Dastgheib Hospital; 🇮🇷 Shiraz, Iran, Islamic Republic of

Kerala Institute of Medical Science (KIMS); 🇮🇳 Kerala, India

Centro Emofilia e Trombosi "Angelo Bianchi Bonomi" Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano - Italy; 🇮🇹 Milano, Italy

Clinica Medica II - Azienda Ospedaliera di Padova - Centro Emofilia di Padova; 🇮🇹 Padova, Italy

Cook Children's Medical Center; 🇺🇸 Fort Worth, Texas, United States

Landes- Frauen- und Kinderklinik Linz Abteilung für Kinder- und Jugendheilkunde; 🇦🇹 Linz, Austria

St. John's Medical College & Hospital; 🇮🇳 Karnataka, India

Hospital de Especialidades UMAE Istituto Mexicano del Seguro Social (IMSS); 🇲🇽 Monterrey (Nuevo Leòn), Mexico

Comprehensive Care Center for Children with Hemophilia Mofid Children Hospital; 🇮🇷 Tehran, Iran, Islamic Republic of

Instituto Nacional de Pediatria; 🇲🇽 México D.F., Mexico

Sahyadri Speciality Hospital; 🇮🇳 Pune, India

Medizinische Universität Wien, Dept. Paediatrics; 🇦🇹 Wien, Austria

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

Centro de Hematologia e Hemoterapia do e.s - Hemoes; 🇧🇷 Vitória, Brazil

Jehangir Clinical Development Centre, Department of Haematology, Jehangir Hospital Premises; 🇮🇳 Pune, India

Ematologia- UO Diagnostica Speciale e Terapia delle Malattie dell'Emostasi e della Trombosi- Università Sapienza - Policlinico Umberto I; 🇮🇹 Rome, Italy

Children's Hospital Los Angeles (CHLA); 🇺🇸 Los Angeles, California, United States

MeritCare Roger Maris Cancer Center, Pediatric Oncology; 🇺🇸 Fargo, North Dakota, United States

Haemophilia Comprehensive Care Clinic, Area 454, Charlotte Maxeke Johannesburg Academic Hospital; 🇿🇦 Parktown, South Africa

Hospital Universitario La Fe Unidad Coagulopatias Congenitas; 🇪🇸 Valencia, Spain

Rush Hemophilia & Trombophilia Center - Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

University of Mississippi Medical Center, Division of pediatric Hematology/Oncology; 🇺🇸 Jackson, Mississippi, United States

Hemophilia and Thrombosis CenterUniversity of Colorado Denver - Anschutz Aurora; 🇺🇸 Aurora, Colorado, United States

Hospital de Ninos Sor Maria Ludovica La Plata Servicio de Hematologia; 🇦🇷 La Plata, Buenos Aires, Argentina

Centre for Blood Disorders; 🇮🇳 Chennai, India

Louisiana Center for Bleeding and Clotting Disorders, Tulane University Medical Center; 🇺🇸 New Orleans, Louisiana, United States

Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States

Hospital de Niños Dr. Luis Calvo Mackenna Centro Hemofílico; 🇨🇱 Santiago, Chile

Paediatric Haematology department, Cairo University Pediatric Hospital; 🇪🇬 Cairo, Egypt

Sir Ganga Ram Hospital; 🇮🇳 New Delhi, India

Kasturba Medical College, Manipal University; 🇮🇳 Karnataka, India

All India Institute of Medical Sciences Department of Haematology; 🇮🇳 New Delhi, India

Hospital Universitario Dr. Josè Eleuterio Gonzalez de la UANL, NL. Mexico; 🇲🇽 Monterrey, Mexico

Hospital Infantil de Mexico Federico Gomez; 🇲🇽 México, D.F., Mexico

Kinf Faisal Specilist Hospital and Research Center; 🇸🇦 Riyadh, Saudi Arabia

Ege Üniversitesi Tip Fakültesi Cocuk Sağliği ve Hastalikari Anabilim Dali Pediatrik Hematoloji Bilim Dali; 🇹🇷 Bornova/Izmir, Turkey

Hospital Universitario Virgen del Rocio Unidad de Hemofilia; 🇪🇸 Sevilla, Spain

Hospital Regional Universitario Carlos Haya; 🇪🇸 Malaga, Spain

Cukurova Universitesi, Tip Fakultesi Pediatrik Hematoloji B.D.; 🇹🇷 Adana, Turkey

Istanbul Üniversitesi Cerrahpaşa Tip Fakültesi Pediatrik Hematoloji B.D.; 🇹🇷 Istanbul, Turkey