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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-007016-15 | EudraCT Number |
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complete per PI
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| Name | Class |
|---|---|
| Charta Foundation | OTHER |
| Grifols Biologicals, LLC | INDUSTRY |
| CSL Behring | INDUSTRY |
| Biotest Pharmaceuticals Corporation |
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This is a prospective, controlled, randomized, open label study, aimed at comparing FVIII/VWF concentrates with FVIII concentrates at 200 IU/kg daily in their ability to induce immune tolerance in Haemophilia A patients with high responding inhibitors and poor prognosis for success.
The presence of Factor VIII (FVIII) inhibitor prevents FVIII infusions from working properly and makes treatment of bleeding episodes very difficult. Having an inhibitor is a serious and life-threatening complication in patients with Hemophilia. The usual treatment of patients with FVIII inhibitors involves "immune tolerance induction" (ITI). Immune Tolerance means that the body can accept infused FVIII and that FVIII is again effective in controlling bleeds. ITI involves giving high doses of FVIII regularly until the inhibitor disappears. This treatment is not always effective. The inhibitor persists in about 1 in 5 patients who undergo ITI.
There are 2 types of FVIII concentrates: FVIII concentrates derived from human plasma, which contain the von Willebrand factor, and concentrates of FVIII without VWF (recombinant or plasma derived). Both types of concentrates are commonly used to induce immune tolerance in patients with Hemophilia A. Retrospective studies in subjects with hemophilia and inhibitors at risk for failing ITI, have indicated a higher rate of success if patients were treated with von Willebrand containing factor VIII concentrates. It is not known whether the addition of Von Willebrand factor offers an advantage to achieving immune tolerance.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| von Willebrand factor-free FVIII concentrates | Active Comparator | Patients treated with FVIII concentrates |
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| FVIII/VWF concentrates | Active Comparator | Patients treated with FVIII/VWF concentrates |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FVIII Concentrates | Drug | Patients will be centrally randomized to receive a von Willebrand factor-free FVIII concentrate (recombinant or plasma-derived, monoclonally-purified). The choice of product brand will be based on physician / patients preferences. |
| Measure | Description | Time Frame |
|---|---|---|
| Primary end point is the success in inducing immune tolerance, defined as: the abolition of the inhibitor to < 0.6 BU within 33 months of ITI with a factor VIII recovery ≥ 66% and half-life ≥ 6 hrs, and measured after a 72-hour washout period. | 33 months |
| Measure | Description | Time Frame |
|---|---|---|
| Absence of relapse, up to 12 months after achievement of Immune Tolerance | 12 months | |
| Time to achieve partial or complete success as defined in the protocol. | 33 months | |
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Inclusion Criteria:
severe hemophilia A (FVIII<1%);
male, any age;
high responders (peak inhibitor levels > 5 BU);
any inhibitor level at study enrolment;
ability and willingness to participate in the study;
at least one of the following risk factors for ITI failure:
absence of high risk of cardiovascular, cerebrovascular or other thromboembolic events as deemed by the treating clinician.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Nadia P Ewing, MD | Clinical Professor of Pediatrics, City of Hope National Medical Center, Dept. of Pediatrics, 1500 E. Duarte Rd. Duarte, CA 91010 | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27214015 | Background | Berntorp E, Ekman M, Gunnarsson M, Nilsson IM. Variation in factor VIII inhibitor reactivity with different commercial factor VIII preparations. Haemophilia. 1996 Apr;2(2):95-9. doi: 10.1111/j.1365-2516.1996.tb00022.x. | |
| Background | Kreutz W: Immune tolerance induction (ITI) in Haemophilia A-patients with inhibitors - the choice of concentrate affecting success. Haematologica2001; 86 (S4):16-20 | ||
| 17610550 |
| Label | URL |
|---|---|
| Related Info | View source |
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| INDUSTRY |
| Grifols Therapeutics LLC | INDUSTRY |
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| FVIII/VWF concentrates | Drug | Patients will be centrally randomized to receive a FVIII/VWF concentrate of 200 IU/Kg by one or two bolus injections daily.The choice of product brand will be based on physician / patients preferences. |
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| Safety Compliance to treatment |
| 33 months |
| Cost of Care | 12 months |
| Background |
| Gringeri A, Musso R, Mazzucconi MG, Piseddu G, Schiavoni M, Pignoloni P, Mannucci PM; RITS-FITNHES Study Group. Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response. Haemophilia. 2007 Jul;13(4):373-9. doi: 10.1111/j.1365-2516.2007.01484.x. |
| Related Info | View source |
| Related Info | View source |
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| Related Info | View source |
| Related Info | View source |
| Related Info | View source |
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D005169 | Factor VIII |
| C078147 | F8 protein, human |
| C427184 | recombinant factor VIII SQ |
| C568131 | optivate |
| C509423 | factor VIII, von Willebrand factor drug combination |
| D014841 | von Willebrand Factor |
| ID | Term |
|---|---|
| D001779 | Blood Coagulation Factors |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011498 | Protein Precursors |
| D001685 | Biological Factors |
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