E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis and treatment of bleeding in patients with Hemophilia B |
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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 | 10060614 |
E.1.2 | Term | Hemophilia B (Factor IX) |
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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 safety (acute effects associated with infusions, and inhibitor development), pharmacokinetics (PK), and efficacy with respect to breakthrough bleeding during prophylaxis and with respect to control of hemorrhaging in both the prophylaxis and on demand groups of IB1001 in subjects with hemophilia B. Acute effects are defined as adverse events (AEs) which occur within the first 72 hours after the administration of a study product. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate markers of thrombogenicity including D-dimer, fragment 1+2 (F1+2), and thrombin-antithrombin III complex (TAT) via plasma levels at time points during the first 24 hours after infusion 2. To obtain information on subject response to an intravenously delivered recombinant factor IX (rFIX) product in terms of tolerance and compliance 3. To estimate the frequency of spontaneous bleeding in subjects with hemophilia B treated on demand 4. To evaluate the ability of IB1001 to provide coverage against bleeding under surgical circumstances, as well as to manage breakthrough bleeding during prophylaxis [does not apply to the UK] 5. To compare the lot consistency of IB1001 across facility preparations, if deemed necessary [does not apply to the UK] 6. To evaluate the long-term safety and efficacy of IB1001 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient must be willing to give written Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent, make the required study visits, and follow instructions while enrolled in the study 2. Severe (factor IX activity ≤2 U/dL) hemophilia B subjects on demand therapy with a minimum of 3 bleeding episodes over the preceding 6 months or 6 bleeding episodes over the preceding 12 months; subjects on prophylaxis with a bleeding pattern as above demonstrated prior to starting prophylaxis 3. Immunocompetent (CD4 count >400/mm3) and not receiving immune modulating or chemotherapeutic agents 4. Previously treated patients with a minimum of 150 exposure days to a factor IX preparation 5. Platelet count at least 150,000/mm3 6. Liver function: alanine transaminase [ALT] and aspartate transaminase [AST] ≤2 times the upper limit of the normal range 7. Total bilirubin ≤1.5 times the upper limit of the normal range 8. Renal function: serum creatinine ≤1.25 times the upper limit of the normal range 9. Willingness to participate in the trial for up to 12-15 months 10. European Union (EU), Israel, and Canada: Age of at least 12 years and body weight of ≥40 kilograms to participate in any PK Study or the Surgical Sub-study [does not apply to the UK]; age of at least 12 years for the prophylaxis and on demand components of the Treatment Phase and Continuation Study United States (US): Age of at least 12 years and body weight of ≥40 kilograms to participate in any PK Study or the Surgical Sub-study; age of at least 5 years for the prophylaxis and on demand components of the Treatment Phase and Continuation Study 11. Hemoglobin ≥7 g/dL at the time of the blood draw
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E.4 | Principal exclusion criteria |
1. History of factor IX inhibitor ≥0.6 Bethesda units (BU) 2. Existence of another coagulation disorder 3. Evidence of thrombotic disease, fibrinolysis, or disseminated intravascular coagulation (DIC) 4. Use of an investigational drug within 30 days prior to study entry 5. On medications that could impact hemostasis, such as aspirin 6. Hypersensitivity to the active substance or to any of the excipients in the investigational products 7. Known allergic reaction to hamster proteins 8. History of poor compliance, a serious medical or social condition, or any other circumstance that, in the opinion of the investigator, would interfere with participation or compliance with the study protocol 9. History of adverse reaction to either plasma-derived factor IX or recombinant factor IX that interfered with the subject’s ability to treat bleeding episodes with a factor IX product |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy- control of break-through bleeding in prophylaxis regimen; assessment of efficacy by patient for each bleeding episode; subject product tolerance.
Safety and Adverse Events monitored by Investigator and subject. Monitoring of inhibitor development and noninhibitory antibodies. Markers of thrombogenicity, samples for CHO assay. |
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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 | 6 |
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 | 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 | 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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The end of the trial is defined by 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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |