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

Primary Purpose

Hemophilia A

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
PLASMA DERIVED Factor VIII
Recombinant FVIII
Sponsored by
Fondazione Angelo Bianchi Bonomi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hemophilia A focused on measuring Hemophilia A, Factor VIII inhibitors, vWF/FVIII, rFVIII

Eligibility Criteria

1 Minute - 6 Years (Child)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • City of Hope National Medical Center
  • Children's Hospital Los Angeles (CHLA)
  • Hemophilia and Thrombosis CenterUniversity of Colorado Denver - Anschutz Aurora
  • Rush Hemophilia & Trombophilia Center - Rush University Medical Center
  • Louisiana Center for Bleeding and Clotting Disorders, Tulane University Medical Center
  • University of Mississippi Medical Center, Division of pediatric Hematology/Oncology
  • Children's Mercy Hospital
  • Hemophilia Treatment Center of Las Vegas
  • MeritCare Roger Maris Cancer Center, Pediatric Oncology
  • Cook Children's Medical Center
  • Hospital de Ninos Sor Maria Ludovica La Plata Servicio de Hematologia
  • Fundacion de la Hemofilia
  • Landes- Frauen- und Kinderklinik Linz Abteilung für Kinder- und Jugendheilkunde
  • Medizinische Universität Wien, Dept. Paediatrics
  • Centro de Pesquisa Clinica HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti
  • Centro de Hematologia e Hemoterapia do e.s - Hemoes
  • Hospital de Niños Dr. Luis Calvo Mackenna Centro Hemofílico
  • Centro de Hemofilicos del Hospital de Niños Roberto del Rio Instituto de Investigaciones Hematologicas
  • Paediatric Haematology department, Cairo University Pediatric Hospital
  • Faculty of Medicine Ain Shams University Department Pediatrics
  • Centre for Blood Disorders
  • St. John's Medical College & Hospital
  • Kasturba Medical College, Manipal University
  • Karnataka Hemophilia Care and Hematology Research Center
  • Kerala Institute of Medical Science (KIMS)
  • Lokmanya TilakMunicipal Medical College &General Hospital - Sion
  • All India Institute of Medical Sciences Department of Haematology
  • Sir Ganga Ram Hospital
  • Sahyadri Speciality Hospital
  • Jehangir Clinical Development Centre, Department of Haematology, Jehangir Hospital Premises
  • Hemophilia Center - Hematoogy & Oncology Dept. Shiraz University of Medical Science Ayatollah Dastgheib Hospital
  • Comprehensive Care Center for Children with Hemophilia Mofid Children Hospital
  • Centro Emofilia e Trombosi "Angelo Bianchi Bonomi" Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano - Italy
  • Clinica Medica II - Azienda Ospedaliera di Padova - Centro Emofilia di Padova
  • Ematologia- UO Diagnostica Speciale e Terapia delle Malattie dell'Emostasi e della Trombosi- Università Sapienza - Policlinico Umberto I
  • Unidad Medica de Alta Especialidad (UMAE), Hospital de Pediatria. Centro Medico Nacional de Occidente Istituto Mexicano del Seguro Social
  • Hospital de Especialidades UMAE Istituto Mexicano del Seguro Social (IMSS)
  • Hospital Universitario Dr. Josè Eleuterio Gonzalez de la UANL, NL. Mexico
  • Instituto Nacional de Pediatria
  • Hospital Infantil de Mexico Federico Gomez
  • Kinf Faisal Specilist Hospital and Research Center
  • Haemophilia Comprehensive Care Clinic, Area 454, Charlotte Maxeke Johannesburg Academic Hospital
  • Hospital Regional Universitario Carlos Haya
  • Hospital Universitario Virgen del Rocio Unidad de Hemofilia
  • Hospital Universitario La Fe Unidad Coagulopatias Congenitas
  • Cukurova Universitesi, Tip Fakultesi Pediatrik Hematoloji B.D.
  • Ege Üniversitesi Tip Fakültesi Cocuk Sağliği ve Hastalikari Anabilim Dali Pediatrik Hematoloji Bilim Dali
  • Istanbul Üniversitesi Cerrahpaşa Tip Fakültesi Pediatrik Hematoloji B.D.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

PLASMA DERIVED Factor VIII

rFVIII

Arm Description

Plasma-derived vWF/FVIII

Recombinant FVIII

Outcomes

Primary Outcome Measures

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
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

To Evaluate the Anamnestic Response of Inhibitor Patients
To Evaluate the Frequency of Transient Inhibitors
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 (Number of EDs)
Number of EDs: Number of Exposure Days (EDs) after which the inhibitors develop
To Evaluate the Modality of Occurrence of Inhibitors (Titre at Onset)
Inhibitor Titre at Onset
To Evaluate Clinical Factors Potentially Associated to Inhibitor Development
To Evaluate Laboratory Factors Potentially Associated to Inhibitor Development
To Evaluate the Incidence of All Other Adverse Events Related and Not Related to the Products Used

Full Information

First Posted
February 4, 2010
Last Updated
July 26, 2017
Sponsor
Fondazione Angelo Bianchi Bonomi
Collaborators
Sintesi Research Srl
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1. Study Identification

Unique Protocol Identification Number
NCT01064284
Brief Title
Survey of Inhibitors in Plasma-Product Exposed Toddlers
Acronym
SIPPET
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
May 2015 (Actual)
Study Completion Date
May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Angelo Bianchi Bonomi
Collaborators
Sintesi Research Srl

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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. .
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
Keywords
Hemophilia A, Factor VIII inhibitors, vWF/FVIII, rFVIII

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
303 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PLASMA DERIVED Factor VIII
Arm Type
Active Comparator
Arm Description
Plasma-derived vWF/FVIII
Arm Title
rFVIII
Arm Type
Active Comparator
Arm Description
Recombinant FVIII
Intervention Type
Drug
Intervention Name(s)
PLASMA DERIVED Factor VIII
Other Intervention Name(s)
ALPHANATE
Intervention Description
Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding
Intervention Type
Drug
Intervention Name(s)
Recombinant FVIII
Other Intervention Name(s)
ADVATE
Intervention Description
Maximum dosage : 50IU per kilo. 2-3 times per week or on demand during acute episode of bleeding
Primary Outcome Measure Information:
Title
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
Description
Expressed with the numebr of patients for each group who developed FVIII inhibitors. PUPs: Previously Untreated Patients MBCTPs: Minimally Blood Component-Treated Patients
Time Frame
During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
Secondary Outcome Measure Information:
Title
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
Title
To Evaluate the Frequency of Transient Inhibitors
Description
Number of participants for each group who developed transient inhibitors (this means, those inhibitors which disappeared spontaneously within 6 months without immunotolerance treatment).
Time Frame
In the 6 months after inhibitor development
Title
To Evaluate the Modality of Occurrence of Inhibitors (Number of EDs)
Description
Number of EDs: Number of Exposure Days (EDs) after which the inhibitors develop
Time Frame
During the first 50 exposure days or first 3 years of enrollment, whichever occurs first
Title
To Evaluate the Modality of Occurrence of Inhibitors (Titre at Onset)
Description
Inhibitor Titre at Onset
Time Frame
During 6 months of observation, from the inhibitor occurrence
Title
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
Title
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
Title
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

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
1 Minute
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pier M. Mannucci, Professor
Organizational Affiliation
Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Flora Peyvandi, Professor
Organizational Affiliation
Fondazione Ca' Granda Ospedale Maggiore Policlinico Milano
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Children's Hospital Los Angeles (CHLA)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Hemophilia and Thrombosis CenterUniversity of Colorado Denver - Anschutz Aurora
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rush Hemophilia & Trombophilia Center - Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Louisiana Center for Bleeding and Clotting Disorders, Tulane University Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
University of Mississippi Medical Center, Division of pediatric Hematology/Oncology
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Hemophilia Treatment Center of Las Vegas
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
MeritCare Roger Maris Cancer Center, Pediatric Oncology
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58102
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Hospital de Ninos Sor Maria Ludovica La Plata Servicio de Hematologia
City
La Plata
State/Province
Buenos Aires
ZIP/Postal Code
1900
Country
Argentina
Facility Name
Fundacion de la Hemofilia
City
Buenos Aires
ZIP/Postal Code
3483
Country
Argentina
Facility Name
Landes- Frauen- und Kinderklinik Linz Abteilung für Kinder- und Jugendheilkunde
City
Linz
ZIP/Postal Code
4020
Country
Austria
Facility Name
Medizinische Universität Wien, Dept. Paediatrics
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Centro de Pesquisa Clinica HEMORIO - Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti
City
Rio de Janeiro
ZIP/Postal Code
20.211-030
Country
Brazil
Facility Name
Centro de Hematologia e Hemoterapia do e.s - Hemoes
City
Vitória
ZIP/Postal Code
29047-100
Country
Brazil
Facility Name
Hospital de Niños Dr. Luis Calvo Mackenna Centro Hemofílico
City
Santiago
ZIP/Postal Code
7500539
Country
Chile
Facility Name
Centro de Hemofilicos del Hospital de Niños Roberto del Rio Instituto de Investigaciones Hematologicas
City
Santiago
ZIP/Postal Code
838-0418
Country
Chile
Facility Name
Paediatric Haematology department, Cairo University Pediatric Hospital
City
Cairo
ZIP/Postal Code
11432
Country
Egypt
Facility Name
Faculty of Medicine Ain Shams University Department Pediatrics
City
Cairo
ZIP/Postal Code
11566
Country
Egypt
Facility Name
Centre for Blood Disorders
City
Chennai
ZIP/Postal Code
600017
Country
India
Facility Name
St. John's Medical College & Hospital
City
Karnataka
ZIP/Postal Code
560034
Country
India
Facility Name
Kasturba Medical College, Manipal University
City
Karnataka
ZIP/Postal Code
576 104
Country
India
Facility Name
Karnataka Hemophilia Care and Hematology Research Center
City
Karnataka
ZIP/Postal Code
577004
Country
India
Facility Name
Kerala Institute of Medical Science (KIMS)
City
Kerala
ZIP/Postal Code
695 029
Country
India
Facility Name
Lokmanya TilakMunicipal Medical College &General Hospital - Sion
City
Mumbai
ZIP/Postal Code
400022
Country
India
Facility Name
All India Institute of Medical Sciences Department of Haematology
City
New Delhi
ZIP/Postal Code
110029
Country
India
Facility Name
Sir Ganga Ram Hospital
City
New Delhi
ZIP/Postal Code
110060
Country
India
Facility Name
Sahyadri Speciality Hospital
City
Pune
ZIP/Postal Code
411 004
Country
India
Facility Name
Jehangir Clinical Development Centre, Department of Haematology, Jehangir Hospital Premises
City
Pune
ZIP/Postal Code
411-001
Country
India
Facility Name
Hemophilia Center - Hematoogy & Oncology Dept. Shiraz University of Medical Science Ayatollah Dastgheib Hospital
City
Shiraz
Country
Iran, Islamic Republic of
Facility Name
Comprehensive Care Center for Children with Hemophilia Mofid Children Hospital
City
Tehran
ZIP/Postal Code
15468-15514
Country
Iran, Islamic Republic of
Facility Name
Centro Emofilia e Trombosi "Angelo Bianchi Bonomi" Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano - Italy
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Clinica Medica II - Azienda Ospedaliera di Padova - Centro Emofilia di Padova
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Ematologia- UO Diagnostica Speciale e Terapia delle Malattie dell'Emostasi e della Trombosi- Università Sapienza - Policlinico Umberto I
City
Rome
ZIP/Postal Code
00161
Country
Italy
Facility Name
Unidad Medica de Alta Especialidad (UMAE), Hospital de Pediatria. Centro Medico Nacional de Occidente Istituto Mexicano del Seguro Social
City
Jalisco
ZIP/Postal Code
44340
Country
Mexico
Facility Name
Hospital de Especialidades UMAE Istituto Mexicano del Seguro Social (IMSS)
City
Monterrey (Nuevo Leòn)
ZIP/Postal Code
64330
Country
Mexico
Facility Name
Hospital Universitario Dr. Josè Eleuterio Gonzalez de la UANL, NL. Mexico
City
Monterrey
ZIP/Postal Code
64450
Country
Mexico
Facility Name
Instituto Nacional de Pediatria
City
México D.F.
ZIP/Postal Code
04530
Country
Mexico
Facility Name
Hospital Infantil de Mexico Federico Gomez
City
México, D.F.
ZIP/Postal Code
06720
Country
Mexico
Facility Name
Kinf Faisal Specilist Hospital and Research Center
City
Riyadh
ZIP/Postal Code
11211
Country
Saudi Arabia
Facility Name
Haemophilia Comprehensive Care Clinic, Area 454, Charlotte Maxeke Johannesburg Academic Hospital
City
Parktown
Country
South Africa
Facility Name
Hospital Regional Universitario Carlos Haya
City
Malaga
ZIP/Postal Code
29011
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio Unidad de Hemofilia
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Universitario La Fe Unidad Coagulopatias Congenitas
City
Valencia
ZIP/Postal Code
46009
Country
Spain
Facility Name
Cukurova Universitesi, Tip Fakultesi Pediatrik Hematoloji B.D.
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Ege Üniversitesi Tip Fakültesi Cocuk Sağliği ve Hastalikari Anabilim Dali Pediatrik Hematoloji Bilim Dali
City
Bornova/Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Istanbul Üniversitesi Cerrahpaşa Tip Fakültesi Pediatrik Hematoloji B.D.
City
Istanbul
ZIP/Postal Code
34300
Country
Turkey

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data (IPD) are available to other researchers through the publication of an article.
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