E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male subjects, aged 6 years to 65 years, with a documented history of moderately severe or severe Hemophilia B (FIX:C≤2%) and with a minimum of 12 bleeding episodes, of which 6 must be joint bleeds, in the 12 months before screening. |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 18.0 |
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 | 100000004850 |
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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 efficacy and safety of BeneFIX infused as prophylaxis regimens, compared with BeneFIX administered in an on-demand regimen only. |
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E.2.2 | Secondary objectives of the trial |
To evaluate and compare the efficacy, safety, and subject-reported outcomes of 2 BeneFIX prophylaxis regimens (100 IU/kg once weekly vs. 50 IU/kg twice weekly), as well as subject-reported outcomes between the prophylaxis regimen and the first on-demand regimen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Documented history of moderately severe or severe hemophilia B (FIX:C ≤ 2%)
2. Male subjects, aged 6 years to 65 years.
3. Subjects with a minimum of 12 bleeding episodes, 6 of which must be joint bleeds, in the 12 months before screening.
4. Written informed consent or assent, as applicable. |
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E.4 | Principal exclusion criteria |
1. Subjects currently utilizing FIX primary prophylaxis
2. For documented HIV+ subjects, CD4 count <200
3. Subjects with hepatic or renal impairment (ALT and AST > 5x ULN, bilirubin >2 mg/dL, serum albumin <LLN, serum creatinine >1.25 x ULN)
4. Prothrombin time > 1.5xULN or INR >1.5.
5. Platelet count < 150,000/µL
6. Subjects who have had major surgery or an orthopedic surgical procedure within the past 3 months
7. Subjects for which major surgery or orthopedic surgery is planned within the duration of the participation in this study
8. Subjects with a past history of, or current FIX inhibitor, defined as >ULN of the reporting laboratory
9. Subjects with a known hypersensitivity to any FIX product or hamster protein
10. Exposure to any investigational drug, except for BeneFIX, or device within 30 days of providing consent/assent (as appropriate) for this study
11. Subjects with bleeding disorders other than hemophilia B
12. Documented concurrent inflammatory disease that in the investigator's judgment could confound the study results (eg: systemic lupus, rheumatoid arthritis or inflammatory bowel disease)
13. Subjects unwilling to adhere to the terms of this protocol
14. Subjects with poor venous access, or who are otherwise inappropriate candidates for this trial in the judgment of the investigator.
15. Subjects committed to an institution by virtue of an order issued by the courts or by a public authority. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint:
1. Annualized number of bleeding episodes
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
This will be analyzed at the end of the study. There is no set visit that will evaluate annual bleeds |
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E.5.2 | Secondary end point(s) |
1. Amount and quality of sleep measured by a Sleep Diary
2. Acute pain scale after hemarthrosis
3.Days lost from work or school after hemarthrosis
4. General health status (SF-36) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For each bleeding event: the sleep diary is filled out on the nights following the bleeding episodes; the acute pain scale and health-related productivity questionnaire diary are filled out on that day and the subsequent day; the SF-36 is filled out at the end of each treatment period. |
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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 | No |
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) | 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 | 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 | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
2 prophylaxis treaments compared with on-demand treatment and comparison of the 2 prophy treatments |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Canada |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial months | 39 |