E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously treated patients with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B undergoing surgical or other invasive procedures |
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E.1.1.1 | Medical condition in easily understood language |
Previously treated patients with severe or moderately severe hemophilia B undergoing surgical or other invasive procedures. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018939 |
E.1.2 | Term | Haemophilia B (Factor IX) |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the hemostatic efficacy and safety of BAX 326 in the peri- and postoperative setting in subjects with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B undergoing major or minor elective or emergency surgical, dental or other invasive procedures. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject is participating in either the BAX 326 Pivotal Study (#250901), the BAX 326 Continuation Study (#251001), or the BAX 326 Pediatric Study (#251101) requiring emergency or elective major or minor surgical, dental, or other invasive procedures a) Subject and/or legal representative has/have provided signed informed consent b) Subject continues to meet eligibility criteria as outlined in the BAX 326 pivotal, continuation or pediatric study. • For newly entering subjects who do not participate in any other BAX 326 clinical study the following inclusion criteria apply: a) Subject is 12 to 65 years old at the time of screening. b) Subject requires elective major surgery. c) Subject and/or legal representative has/have provided signed informed consent d) Subject has severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B (based on the one stage activated partial thromboplastin time (aPTT) assay), as tested at screening at the central laboratory. e) Subject is previously treated with plasma-derived and/or recombinant FIX concentrate(s) for a minimum of 150 EDs (based and documented on the subject’s medical records). f) Subject has no evidence of a history of FIX inhibitors (based on the subject’s medical records). g) Subject is immunocompetent as evidenced by a CD4 count ≥ 200 cells/mm3. h) Subject is human immunodeficiency (HIV) negative or is HIV+ with a viral load < 200 particles/μL ~ <400,000 copies/mL i) If female of childbearing potential, subject presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study. j) Subject is willing and able to comply with the requirements of the Protocol |
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E.4 | Principal exclusion criteria |
For newly entering subjects who do not participate in any other clinical study with BAX 326 the following exclusion criteria apply: a) The subject has a history of FIX inhibitors with a titer ≥ 0.6 Bethesda Units (BU) (as determined by the Nijmegen modification of the Bethesda assay or the assay employed in the respective local laboratory) at any time prior to screening. b) The subject has a detectable FIX inhibitor at screening, with a titer ≥0.6 BU as determined by the Nijmegen modification of the Bethesda assay in the central laboratory. c) The subject requires emergency surgery. d) The subject’s weight is < 35 kg or > 120 kg e) The subject has a history of allergic reaction, eg, anaphylaxis, following exposure to FIX concentrate(s). f) The subject has a known hypersensitivity to hamster proteins or rFurin. g) The subject has evidence of an ongoing or recent thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC). h) The subject has an abnormal renal function (serum creatinine > 1.5 times the upper limit of normal). The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices. i) The subject has active hepatic disease with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 5 times the upper limit of normal. j) The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia B. k) The subject’s platelet count is < 100,000/mL. l) The subject has a clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject’s safety or compliance. m) The subject is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug (eg, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day, or α-interferon) other than anti-retroviral chemotherapy. n) The subject has participated in another investigational study within 30 days of enrollment. o) The subject is a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (i.e., children, partner/spouse, siblings, parents) as well as employees.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Hemostatic efficacy a) Intraoperative hemostatic efficacy 1. Intraoperative Hemostatic Efficacy Assessment on a scale of “excellent”, “good”, “fair” and “none” 2. Actual intraoperative blood loss compared to average and maximum blood loss predicted preoperatively b) Postoperative hemostatic efficacy 1. Postoperative Hemostatic Efficacy Assessment at the time of drain removal, if applicable,or at postoperative day 3 (approximately 72 hours postoperatively) in case of major surgery and no drain employed on a scale of “excellent”, “good”, “fair” and “none” 2. Postoperative Hemostatic Efficacy Assessment at the time of discharge from the hospital on a scale of “excellent”, “good”, “fair” and “none” 3. Actual postoperative blood loss until drain removal, if applicable, compared to average and maximum blood loss predicted preoperatively c) BAX 326 consumption and blood product use 1. Daily and total weight-adjusted dose of BAX 326 per subject 2. Number of units and amount (in mL) of blood product transfused • Safety a) Development of inhibitory and total binding antibodies to FIX b) IP-related AEs • Determine the occurrence of thrombotic events • Presurgical Pharmacokinetics (only in subjects undergoing major elective surgery who did not undergo a PK assessment in the pivotal study) a) Area under the plasma concentration versus time curve from 0 to 72 hours/dose (AUC0-72 h/dose), total AUC/dose, mean residence time (MRT), clearance (CL), Incremental Recovery (IR), elimination phase half-life (T1/2), and volume of distribution at steady state (Vss)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Hemostatic efficacy: intraoperative and postoperative at drain removal or postoperative day 3, as well as at discharge. Safety:end of trial |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Chile |
Colombia |
Japan |
Russian Federation |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last Subject Out after approximately 30 surgical procedures in approximately 30 subjects. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |