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 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018939 |
E.1.2 | Term | Haemophilia B (Factor IX) |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 immunogenicity of glycopegylated recombinant coagulation factor IX (NNC-0156-
0000-0009; hereafter referred to as N9-GP) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate safety other than immunogenicity of N9-GP
- To evaluate the efficacy of N9-GP in long-term prophylaxis and in the treatment of breakthrough bleeding episodes
- To evaluate the efficacy of N9-GP through the surrogate marker for efficacy, FIX activity
- To evaluate the pharmacokinetic (PK) properties of N9-GP |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male patients with moderately severe or severe congenital haemophilia B with a FIX activity level ≤2% according to medical records
- Age ≤12 years (until patient turns 13 years, at time of inclusion)
- Body weight ≥10 kg
- History of at least 50 exposure days (EDs) to other FIX products
- The patient and/or parent(s)/caregiver are capable of assessing a bleeding episode, keeping an electronic diary (eDiary), capable of conducting home treatment and otherwise able to follow trial procedures |
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E.4 | Principal exclusion criteria |
- Known history of FIX inhibitors
- Current FIX inhibitors ≥0.6 Bethesda Units (BU)
- Congenital or acquired coagulation disorder other than haemophilia B
- Platelet count <50,000/μL at screening
- Alanine aminotransferase (ALT) >3 times the upper limit of normal reference ranges at screening
- Creatinine level ≥ 1.5 times above the upper normal limit of normal reference ranges at screening
- Human immunodeficiency virus (HIV) positive, defined by medical records, and with a CD4+ lymphocyte count ≤200/μL
- Immune modulating or chemotherapeutic medication (except single pulse treatment, inhaled and topical steroids)
- Previous arterial thrombotic events (myocardial infarction and intracranial thrombosis, as defined by medical records) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of inhibitory antibodies against coagulation factor IX (FIX) defined as titre ≥0.6 BU |
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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) |
1 - Number of bleeding episodes during prophylaxis
2 - Haemostatic effect of N9-GP in treatment of bleeding episodes by 4-point categorical scale for haemostatic response (excellent, good, moderate and poor)
3 - Incremental recovery at 30 minutes (IR30min)
4 - Trough level single-dose
5 - Trough level steady state
6 - Terminal half-life (t1/2) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - Week 52
2 - Week 52
3 - Week 0
4 - Week 0
5 - Week 4-44
6 - Week 0 |
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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 | 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 | 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) | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Brazil |
Canada |
Croatia |
France |
Germany |
Ireland |
Israel |
Italy |
Japan |
Malaysia |
Romania |
Taiwan |
Thailand |
Turkey |
United Kingdom |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |