E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A study on prophylaxis and treatment of a non-plasma source (recombinant) product that replaces the missing clotting factor IX in patients with severe Hemophilia B. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
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 | 100000004850 |
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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 |
The primary objectives of the study are to evaluate the efficacy of rIX-FP in preventing bleeding episodes (prophylaxis) and safety of rIX-FP with respect to the development of inhibitors to FIX in patients with severe hemophilia B. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: •To evaluate the safety of rIX-FP, based on AEs and the development of antibodies to rIX-FP. •To evaluate the clinical response to rIX-FP for the prevention and treatment of bleeding episodes in patients with severe hemophilia B. •To evaluate the efficacy of rIX-FP in surgical prophylaxis. •To evaluate the pharmacokinetics (PK) of a single dose of rIX-FP.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The primary objective of the sub-study is to evaluate the efficacy of rIX-FP in the prevention and control of bleeding in patients with severe to moderate hemophilia B during surgical procedures. The secondary objective of the study is to evaluate the safety of rIX-FP during the intraoperative and postoperative periods. |
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E.3 | Principal inclusion criteria |
• Male subjects, 12 to 65 years old. • Severe hemophilia B (FIX activity of ≤ 2%). • Subjects who have received FIX products (plasma-derived and/or recombinant FIX) for > 150 exposure days (EDs). • No history of FIX inhibitor formation, no detectable inhibitors at Screening and no family history of inhibitors against FIX. • Written informed consent for study participation. • On-demand subjects only, who have experienced a minimum average of 2 non-trauma induced bleeding episodes requiring treatment with a FIX product during the previous 6 or 3 months.
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E.4 | Principal exclusion criteria |
• Known hypersensitivity to any FIX product or hamster protein. • Known congenital or acquired coagulation disorder other than congenital FIX deficiency. • HIV positive subjects with a CD4 count < 200/mm3. • Low platelet count, kidney or liver dysfunction. • Recent life-threatening bleeding episode.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in frequency of spontaneous bleeding events between on-demand and prophylaxis treatments (annualized)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- The frequency of related Adverse Events (AEs) to rIX-FP over the course of the study. - The number of subjects with antibodies against rIX-FP. - Proportion of bleeding episodes requiring one or ≤ two infusions of rIX-FP to achieve hemostasis. - Investigator’s overall clinical assessment of hemostatic efficacy for treatment of bleeding episodes, based on a four point ordinal scales (excellent, good, moderate, poor/ none). - rIX-FP consumed per month while maintaining assigned prophylactic treatment interval during routine prophylaxis. - Incremental recovery (IU/mL/IU/kg) at 30 minutes following infusion of rIX-FP. - Half-life (t1/2) of a single dose of rIX-FP. - AUC to the last sample with quantifiable drug concentration (AUC0-t) of a single dose of rIX-FP. - Clearance of a single dose of rIX-FP. - Annualized spontaneous bleeding events during the 7 day prophylactic regimen period compared to the annualized spontaneous bleeding events during each of the prophylactic regimens longer than the 7 day prophylactic regimen period. - Investigator’s (or surgeon’s) overall clinical assessment of hemostatic efficacy for surgical prophylaxis, based on a four point ordinal scale (excellent, good, moderate, poor/ none) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All timepoints are approximately 14 months except for the PK endpoints, which are 240 hours or as indicated in the endpoint description, and the Investigator's overall clinical assessment of hemostatic efficacy for surgical prophylaxis, which is approximately 14 days. |
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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 | No |
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) | 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) | 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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Different treatment schedule - On demand arm (as detailed in the protocol) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Bulgaria |
France |
Italy |
Japan |
Austria |
Germany |
Spain |
Israel |
Russian Federation |
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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The end of study participation for an individual subject occurs with the end of the follow-up period, which is defined as completion of the final study visit, after which no further study-related procedures will be performed. |
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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 | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |