Inhibitor Development in Previously Untreated Patients (PUPs) or Minimally Blood Component-Treated Patients (MBCTPs) when exposed to von Willebrand factor-containing factor VIII concentrates and to Recombinant factor VIII concentrates: Indipendent, International, Multicenter, Prospective, Controlled, Randomized, Open-label
Inhibitor development is the most challenging complication of hemophilia treatment and the highest economic burden for a chronic disease.
It is essential to know whether plasma-derived and recombinant products are associated with a different risk of inhibitor development in previously untreated patients or not.
A number of risk factors have been identified for the development of FVIII inhibitors in children with hemophilia A, including: disease severity, defects in the FVIII gene causing hemophilia in child, ethnicity and number of exposure days (EDs) to FVIII.
No randomized clinical trials are available to provide the evidence needed: it was not possible to reach definitive conclusions on the incidence of inhibitors with each of the FVIII products, because of differences in study design of safety trials.
Since it is not known whether recombinant FVIII products are more immunogenic than plasma derived, there is a need of randomized clinical trials to provide a definitive answer on the different immunogenicity of FVIII products.
WHAT IS THE SIPPET STUDY?
SIPPET is an international, multicenter, prospective, controlled, randomized and open-label clinical study.
About 50 research centers around the world are seeking for approximately 300 PU patients or MBCT patients.
Eligible patients will be enrolled at each participating centre, randomized to be treated exclusively with a single FVIII product either plasma-derived and containing VWF or recombinant, and followed up until inhibitor development or until 50 exposure days (EDs) or 3 years from enrolment have elapsed, whichever comes first.
WHAT ARE THE STUDY OBJECTIVES?
The study aims to assess the immunogenicity of VWF/FVIII and of rFVIII concentrates by determining the frequency of inhibitor development in PUPs and MBCTs in the first 50 EDs or in the first 3 years from enrolment, whichever comes first.
Other relevant objectives will be the evaluation of the anamnestic response of inhibitor patients to evaluate the frequency of transient inhibitors, to assess the modality of occurrence of inhibitors (number of EDs, titre at onset and so on …) and the clinical factors potentially associated to inhibitor development (age at first treatment, severity of bleeding episodes, surgery, intensity of treatment, modality of treatment, time of treatment in relation to vaccinations, concurrent diseases - in particular viral infections- , complications of venous access and/or medications, type of delivery, breast feeding, type of milk formula).
WHO IS ELIGIBLE FOR THE TRIAL?
Previously untreated male subjects of any ethnicity, aged <6 years with severe hemophilia A.
HEMOPHILIA A FACTS
Approximately one in 5,000 males born has haemophilia (US data). All races and economic groups are affected equally. Approximately 70% of people around the world do not have access to treatment.
Currently, there is no cure for hemophilia. While treatment exists, it is costly and may require lifelong infusion of replacement clotting factor manufactured either from human plasma or using recombinant technology.
Hemophilia occurs predominately in males. In about one-third of cases there is no known family history of hemophilia. Instead the disorder results from a spontaneous genetic mutation.
SIPPET TRIAL SPONSOR
The SIPPET study is worldwide sponsored by the A. Bianchi Bonomi Fondation.
People interested in learning more about the study may send an e-mail to: