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

July 26, 2017 updated by: Fondazione Angelo Bianchi Bonomi

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

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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Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

303

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, 3483
        • Fundacion de la Hemofilia
    • Buenos Aires
      • La Plata, Buenos Aires, Argentina, 1900
        • Hospital de Ninos Sor Maria Ludovica La Plata Servicio de Hematologia
  • Austria
      • Linz, Austria, 4020
        • Landes- Frauen- und Kinderklinik Linz Abteilung für Kinder- und Jugendheilkunde
      • Wien, Austria, 1090
        • Medizinische Universität Wien, Dept. Paediatrics
  • Brazil
      • Rio de Janeiro, Brazil, 20.211-030
        • Centro de Pesquisa Clinica HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti
      • Vitória, Brazil, 29047-100
        • Centro de Hematologia e Hemoterapia do e.s - Hemoes
  • Chile
      • Santiago, Chile, 7500539
        • Hospital de Niños Dr. Luis Calvo Mackenna Centro Hemofílico
      • Santiago, Chile, 838-0418
        • Centro de Hemofilicos del Hospital de Niños Roberto del Rio Instituto de Investigaciones Hematologicas
  • Egypt
      • Cairo, Egypt, 11432
        • Paediatric Haematology department, Cairo University Pediatric Hospital
      • Cairo, Egypt, 11566
        • Faculty of Medicine Ain Shams University Department Pediatrics
  • India
      • Chennai, India, 600017
        • Centre for Blood Disorders
      • Karnataka, India, 560034
        • St. John's Medical college & Hospital
      • Karnataka, India, 576 104
        • Kasturba Medical College, Manipal University
      • Karnataka, India, 577004
        • Karnataka Hemophilia Care and Hematology Research Center
      • Kerala, India, 695 029
        • Kerala Institute of Medical Science (KIMS)
      • Mumbai, India, 400022
        • Lokmanya TilakMunicipal Medical College &General Hospital - Sion
      • New Delhi, India, 110060
        • Sir Ganga Ram Hospital
      • New Delhi, India, 110029
        • All India Institute of Medical Sciences Department of Haematology
      • Pune, India, 411 004
        • Sahyadri Speciality Hospital
      • Pune, India, 411-001
        • Jehangir Clinical Development Centre, Department of Haematology, Jehangir Hospital Premises
  • Iran, Islamic Republic of
      • Shiraz, Iran, Islamic Republic of
        • Hemophilia Center - Hematoogy & Oncology Dept. Shiraz University of Medical Science Ayatollah Dastgheib Hospital
      • Tehran, Iran, Islamic Republic of, 15468-15514
        • Comprehensive Care Center for Children with Hemophilia Mofid Children Hospital
  • Italy
      • Milano, Italy, 20122
        • Centro Emofilia e Trombosi "Angelo Bianchi Bonomi" Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano - Italy
      • Padova, Italy, 35128
        • Clinica Medica II - Azienda Ospedaliera di Padova - Centro Emofilia di Padova
      • Rome, Italy, 00161
        • Ematologia- UO Diagnostica Speciale e Terapia delle Malattie dell'Emostasi e della Trombosi- Università Sapienza - Policlinico Umberto I
  • Mexico
      • Jalisco, Mexico, 44340
        • Unidad Medica de Alta Especialidad (UMAE), Hospital de Pediatria. Centro Medico Nacional de Occidente Istituto Mexicano del Seguro Social
      • Monterrey, Mexico, 64450
        • Hospital Universitario Dr. Josè Eleuterio Gonzalez de la UANL, NL. Mexico
      • Monterrey (Nuevo Leòn), Mexico, 64330
        • Hospital de Especialidades UMAE Istituto Mexicano del Seguro Social (IMSS)
      • México D.F., Mexico, 04530
        • Instituto Nacional de Pediatría
      • México, D.F., Mexico, 06720
        • Hospital Infantil de Mexico Federico Gomez
  • Saudi Arabia
      • Riyadh, Saudi Arabia, 11211
        • Kinf Faisal Specilist Hospital and Research Center
  • South Africa
      • Parktown, South Africa
        • Haemophilia Comprehensive Care Clinic, Area 454, Charlotte Maxeke Johannesburg Academic Hospital
  • Spain
      • Malaga, Spain, 29011
        • Hospital Regional Universitario Carlos Haya
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio Unidad de Hemofilia
      • Valencia, Spain, 46009
        • Hospital Universitario La Fe Unidad Coagulopatias Congenitas
  • Turkey
      • Adana, Turkey, 01330
        • Cukurova Universitesi, Tip Fakultesi Pediatrik Hematoloji B.D.
      • Bornova/Izmir, Turkey, 35100
        • Ege Üniversitesi Tip Fakültesi Cocuk Sağliği ve Hastalikari Anabilim Dali Pediatrik Hematoloji Bilim Dali
      • Istanbul, Turkey, 34300
        • Istanbul Üniversitesi Cerrahpaşa Tip Fakültesi Pediatrik Hematoloji B.D.
  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles (CHLA)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Hemophilia and Thrombosis CenterUniversity of Colorado Denver - Anschutz Aurora
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush Hemophilia & Trombophilia Center - Rush University Medical Center
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Louisiana Center for Bleeding and Clotting Disorders, Tulane University Medical Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center, Division of pediatric Hematology/Oncology
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Hemophilia Treatment Center of Las Vegas
    • North Dakota
      • Fargo, North Dakota, United States, 58102
        • MeritCare Roger Maris Cancer Center, Pediatric Oncology
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 minute to 6 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: PLASMA DERIVED Factor VIII
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 Names:
  • 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 Names:
  • ADVATE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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
During the first 50 exposure days or first 3 years of enrollment, whichever occurs first

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To Evaluate the Anamnestic Response of Inhibitor Patients
Time Frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Frequency of Transient Inhibitors
Time Frame: 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).
In the 6 months after inhibitor development
To Evaluate the Modality of Occurrence of Inhibitors (Number of EDs)
Time Frame: 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
During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate the Modality of Occurrence of Inhibitors (Titre at Onset)
Time Frame: During 6 months of observation, from the inhibitor occurrence
Inhibitor Titre at Onset
During 6 months of observation, from the inhibitor occurrence
To Evaluate Clinical Factors Potentially Associated to Inhibitor Development
Time Frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
To Evaluate Laboratory Factors Potentially Associated to Inhibitor Development
Time Frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
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
Time Frame: During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
During the first 50 exposure days or first 3 years of enrollment, whichever occurs first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Angelo Bianchi Bonomi

Collaborators

Sintesi Research Srl

Investigators

  • Principal Investigator: Pier M. Mannucci, Professor, Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano
  • Principal Investigator: Flora Peyvandi, Professor, Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (Actual)

May 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

February 4, 2010

First Submitted That Met QC Criteria

February 5, 2010

First Posted (Estimate)

February 8, 2010

Study Record Updates

Last Update Posted (Actual)

August 25, 2017

Last Update Submitted That Met QC Criteria

July 26, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ABB - 09 - 001
  • 2009-011186-88 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data (IPD) are available to other researchers through the publication of an article.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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