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

This study has been completed.
Sponsor:
Collaborator:
Sintesi Research Srl
Information provided by (Responsible Party):
Fondazione Angelo Bianchi Bonomi
ClinicalTrials.gov Identifier:
NCT01064284
First received: February 4, 2010
Last updated: July 26, 2017
Last verified: July 2017
  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.


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: None (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:


Further study details as provided by Fondazione Angelo Bianchi Bonomi:

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 [ 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



Secondary Outcome Measures:
  • 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 ]
  • 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).

  • 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

  • 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

  • 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 ]
  • 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 ]
  • 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 ]

Enrollment: 303
Study Start Date: January 2010
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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   (Child)
Sexes 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 48 Study Locations
Sponsors and Collaborators
Fondazione Angelo Bianchi Bonomi
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
  More Information

Additional Information:
Publications:
Qadura M, Waters B, Burnett E, Chegeni R, Othman M, Lillicrap D. Investigating the mechanisms underlying FVIII antibody production in hemophilic mice following recombinant and plasma-derived FVIII infusion. Blood (ASH Annual Meeting Abstracts) 2008; 112: abstract #237.

Study Data/Documents: Article  This link exits the ClinicalTrials.gov site
Identifier: NEJM2016;374:2054-206
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: SIPPET ABB-09-001 V02 27Jan14

People interested in learning more about the study may send an e-mail to:

sippet-info@sintesiresearch.com


Statistical Analysis Plan  This link exits the ClinicalTrials.gov site

Interim Statistical Analysis Plan was released on 14 April 2014.

People interested in learning more about the study may send an e-mail to:

sippet-info@sintesiresearch.com



Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fondazione Angelo Bianchi Bonomi
ClinicalTrials.gov Identifier: NCT01064284     History of Changes
Other Study ID Numbers: ABB - 09 - 001
2009-011186-88 ( EudraCT Number )
Study First Received: February 4, 2010
Results First Received: December 2, 2016
Last Updated: July 26, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) are available to other researchers through the publication of an article.

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

ClinicalTrials.gov processed this record on September 21, 2017