E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
to expose up to 50 patients aged 12-64 years, and approximately 20 patients up to 11 years of age with severe or moderately severe hemophilia B to IMMUNINE for a period of approximately 20 to 50 exposure days (EDs) prospectively document the exposure days (EDs) and development of factor IX (FIX) inhibitionors if any, while receiving prophylactic treatment so that these patients can transition into the BAX 326 pivotal or pediatric study evaluating a new rFIX. |
|
E.1.1.1 | Medical condition in easily understood language |
Severe to moderately severe Hemophilia B, i.e. lack of (active) blood
clotting factor IX |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060614 |
E.1.2 | Term | Hemophilia B (Factor IX) |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 |
E.2.1 Main objective: To prospectively document the exposure to IMMUNINE and to monitor FIX inhibition while receiving prophylactic treatment over a period of approximately 20 to 50 EDs in a up to 50 PTPs aged 12-64 years and approximately 20 pediatric subjects up to 11 years of age with severe (FIX level <1% or moderately severe (FIX level <= 2%) hemophilia B who are planned to enter BAX 326 pivotal or pediatric study evaluating a new rFIX, provided all eligibility criteria are met |
|
E.2.2 | Secondary objectives of the trial |
E.2.2 S econdary objectives::
•to evaluate safety in terms of investigational product related adverse events, immunogenicity and thrombogenicity, routine laboratory parameters (hematology/clinical chemistry) and vital signs.
• to monitor haemostatic efficacy of IMMUNINE in the management and prevention of acute bleeding episodes and surgical prophylaxis (if necessary)-
•to evaluate the subject’s compliance with the protocol study specific treatment regimen
•to monitor incremental recovery of IMMUNINE over time
•to evaluate HR QoL at baseline
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Subject and/or legal representative has/have provided signed informed consent.
•Subject is up to 64 years old at the time of screening.
•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.
•Subject is previously treated with plasma-derived or recombinant FIX concentrate(s), cryoprecipitate or fresh frozen plasma (FFP) for approximately 100 - 150 exposure days (EDs) if > = 6 years old or 20-50 ED if < 6 years old and is planned to enter either the Study BAX326 pivotal or BAX 326 pediatric study. The number of EDs is derived from the subject’s treatment regimen and his/her bleeding pattern.
•Subject is willing to receive prophylactic treatment for the duration of the study.
•Subject is immunocompetent as evidenced by a CD4 count ≥ 200 cells/mm.
•Subject is human immunodeficiency virus (HIV) negative or is HIV+ with a viral load < 200 particles/μL, approximately <400,000 copies/mL.
•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.
Subject/legal representative is willing and able to comply with the requirements of the protocol.
|
|
E.4 | Principal exclusion criteria |
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.
•The subject has a history of FIX inhibitors with a titer ≥ 0.6 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.
•The subject has a history of allergic reaction, eg, anaphylaxis, following exposure to FIX concentrate(s).
•The subject has evidence of a thrombotic disease, fibrinolysis or disseminated intravascular coagulation (DIC).
•Subject is scheduled for elective surgery, unless the surgery is medically required within the anticipated study period
•The subject has an abnormal renal function (serum creatinine > 1.5 times the upper limit of normal [ULN]).
•The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) exceeding the upper limit of normal hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.
•The subject has active hepatic disease with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥ 5 times the upper limit of normal. During the study, subjects with chronic hepatitis B or C may have fluctuations of up to 5 times the upper limit of normal but will not require discontinuation.
•The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia B.
•The subject’s platelet count is < 100,000/mL.
•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.
•The subject is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug other than anti-retroviral chemotherapy (eg, α-interferon, corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day).
•The subject is pregnant or lactating at the time of study enrollment.
•The subject is unwilling to consider further participation in the BAX326 (rFIX) pivotal or pediatric study.
•Subject has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment.
•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 (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of the study is to prospectively document
exposure to IMMUNINE and to monitor FIX inhibitors for approximately
20 to 50 EDs in up to 50 PTPs with severe or moderately severe
hemophilia B so that these patients can transition into BAX326 study
250901 provided all eligibility criteria are met. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary study objectives are the evaluation of efficacy, safety,
immunogenicity, thrombogenicity, HR QoL, and the subject's compliance
with the study specific treatment regimen. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of Study; QoL at screening |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | Yes |
E.6.13 | Others | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Bulgaria |
Chile |
Colombia |
Czech Republic |
Poland |
Romania |
Russian Federation |
Ukraine |
|
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
|
Last Visit of the Last Subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |