E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe or Moderately Severe Hemophilia B Patients |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016077 |
E.1.2 | Term | Factor IX deficiency |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Pharmacokinetics (PK) evaluation in vivo incremental recovery; area under the curve (AUC);area under the moment curve (AUMC); plasma half-life (tœ),determination of the time necessary to reach the peak plasma concentration (Tmax),clearance (CL), mean permanence time (MRT),distribution volume at steady state (Vdss),peak plasma concentration (Cmax) Efficacy and Safety evaluation Efficacy: 1) Evaluation of the haemostatic efficacy of Kedrion human plasma-derived double virus inactivated and nanofiltered factor IX (henceforth: Investigational Medicinal Product- IMP) in the management of acute bleeding events. Safety: 1) Assessment of the risk of inhibitor (neutralizing anti factor IX antibodies) development in conjunction with infusion of the IMP throughout the study period 2) Assessment of thrombogenicity of the IMP 3) Assessment of the short and medium term safety of the IMP, when administered to severe/moderately severe Previously Treated Patients |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Age ≥ 12 years. 2. Weight > 35 kg 3. Subjects should have severe or moderately severe haemophilia B as defined by a baseline factor IX level 2%, documented at pre-enrolment screening (see Section 7.1) on the basis of anamnesis data (i.e., at haemophilia diagnosis). 4. Prior to study entry, subjects should have a history of at least 150 exposure days for all types of factor IX containing products, including fresh frozen plasma (FFP). This minimum exposure rate shall be estimated by the haemophilia treating physician. 5. If subjects are HIV-1 seropositive they should have a CD4+ lymphocyte count ≥ 400/l documented on 2 consecutive occasions over a 12 months period prior to study entry. The latest CD4+ lymphocyte count qualifying the patient for enrolment (i.e. ≥ 400/l) should be within 6 months before enrolment in the study. 6. Subjects, or their legally authorised representative in the case of study participants ≥ 12 and < 18 years of age, should have been informed of the nature of the study, agreed to its provision, and signed dated the informed consent approved by the IRB/IEC. 7. Subjects who will be available for the duration of the study will be included. At study entry all patients will be screened for the presence of HAV and HBV Antibodies; all HBV and/or HAV test negative patients will be vaccinated against Hepatitis B and/or hepatitis A before entering the study. |
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E.4 | Principal exclusion criteria |
The following subjects will be ineligible for enrolment: 1. Subjects with a detectable inhibitor to factor IX at the time of enrolment or a history of inhibitor to factor IX (> 0.6 BU). 2. Subjects with clinical or laboratory evidence of portal vein hypertension, such as an international normalized ratio (INR) > 1.4, the presence of splenomegaly and/or spider angiomata on physical examination and/or a history of oesophageal haemorrhage or documented oesophageal varices. 3. Subjects HIV positive who are treated with highly active anti-retroviral therapy (HAART) regimen. 4. Subjects with any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives, or participation in this trial. 5. Subjects unwilling to give written informed consent to participation, or who have participated in another clinical trial within 1 month before study initiation, i.e. they have received any test drug within 30 days prior the study. The Investigator will make sure that the patients are not planning to leave the area of the study site before the end of the study period. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of pharmacokinetics, efficacy and safety of IMP |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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) | 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.8.3 |
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.8.5 | The trial involves multiple Member States | No |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |