E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The medical condition to be investigated is Hemophilia B, or Christmas disease. Hemophilia B is a deficiency in the clotting FIX and is a recessively inherited coagulation disorder due to an X-chromosome mutation carried by females and expressed mainly by males, affecting approximately 80,000 people worldwide. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053754 |
E.1.2 | Term | Hemophilia B without inhibitors |
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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 |
The primary objectives of the study are:
To evaluate the safety and tolerability of rFIXFc
To evaluate the efficacy of rFIXFc in the 2 prevention regimens:
o Arm 1 (Prevention Regimen, Fixed-Weekly Interval)
o Arm 2 (Prevention Regimen, Individualized Interval)
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
To evaluate and assess the PK parameter estimates of rFIXFc and BeneFIX at baseline in the Sequential PK subgroup as well as rFIXFc at Week 26 (± 1 week)
To evaluate the efficacy of rFIXFc used on-demand and surgical subgroup
To evaluate subjects’ response to treatment
To evaluate rFIXFc consumption
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible to participate in this study, candidates must meet the following eligibility criteria at Screening:
1-Able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. If the subject is younger than 18 years old, then a parent or guardian needs to sign the ICF and the subject needs to sign the assent form as consistent with local authorities.
2-Male ≥12 years of age, and weigh at least 40 kg
3-Severe hemophilia B defined as ≤2 IU/dL (≤2%) endogenous FIX documented in the medical record
4-A previously treated subject, defined as having at least 100 prior exposure days to any FIX product (historical data from subject records and/or subject history)
5-Bleeding events and/or treatment with FIX during the last 3 months as documented in the subjects’ medical records
6-Greater than or equal to 4 bleeds in the 6 months prior to enrollment in the study if currently treating with an on-demand regimen.
7-At least 4 days since the subject’s last dose of FIX.
8-A platelet count ≥100,000 cells/µL
9-CD4 count ≥200 cells/µL if subject is HIV antibody positive, based on recent lab result (within one year)
10-An INR ≤1.3 as defined by the testing laboratory’s normal range
11-For subjects entering directly into Treatment Arm 4 (Surgery), the subject meets all other eligibility criteria AND requires a major elective surgery defined as surgery that requires at least 4 days of FIX coverage.
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E.4 | Principal exclusion criteria |
Candidates will be excluded from study entry if any of the following exclusion criteria exist at Screening:
1. Prior history of, or currently detectable inhibitor as defined by the reporting laboratory (family history of inhibitors will not exclude the subject)
2. Other coagulation disorder(s) in addition to hemophilia B
3. Prior history of anaphylaxis associated with any FIX or IV immunoglobulin administration.
4. Abnormal renal function defined as serum creatinine >2.0 mg/dL
5. Active hepatic disease defined as an AST or ALT greater than 5 times the upper limit of normal
6. For Sequential PK subgroup: allergy to Chinese Hamster proteins
7. Any concurrent clinically significant major disease that, in the opinion of the Investigator, makes the subject unsuitable for enrollment
8. Concurrent systemic treatment with immunosuppressant drugs within the last 3 months prior to the study entry (allowed: interferon-α for hepatitis C, highly active antiretroviral treatment [HAART] for HIV and/or steroids [2 pulse treatments / 7 days ≤1 mg/kg])
9. Current treatment with any investigational product or medical device within the past 30 days of the first dose of study treatment.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and tolerability endpoints include clinically notable changes from baseline in physical examinations, vital signs, laboratory values, and the incidence of AEs, including the incidence of inhibitor development.
The number of breakthrough bleeding episodes (spontaneous and traumatic) with rFIXFc per subject annualized over the study period.
Safety endpoint – involves all arms
Number of bleeds endpoint – concerns the two prevention arms only |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Only the sequential PK part of the study is controlled. Other parts of the study are not controlled |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 study is defined as the time point when: •13 evaluable subjects in the Sequential PK subgroup reach 50 exposure days AND;
•7 evaluable non Sequential PK subgroup subjects in Arm 1 reach 50 exposure days AND;
•20 evaluable subjects in Arm 2 have at least 26 weeks on study AND;
•16 evaluable subjects in Arm 3 have at least 26 weeks on study AND;
•10 major surgeries ("in at least 5 subjects" to 10 major surgeries) have been performed and post-operative follow-up completed. |
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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 | 0 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 0 |