E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haemophilia A with anti factor VIII and Haemophilia B with anti factor IX |
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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 | 10056492 |
E.1.2 | Term | Haemophilia A with anti factor VIII |
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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 | 10056494 |
E.1.2 | Term | Haemophilia B with anti 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 of five escalating doses of NN1731 in haemophilia subjects with inhibitors being treated for acute joint bleeds. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of NN1731 for treatment of acute joint bleeds in haemophilia subjects with inhibitors •To evaluate the immunogenicity of NN1731 •To evaluate the pharmacokinetics of NN1731
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the subject.) 2.Clinical diagnosis of congenital haemophilia A or B with a current or historical peak inhibitor of >5 BU to human FVIII or IX and known anti-human FVIII or IX anamnestic response 3.Male subject, 18 years of age or older (≥18 years old in UK) 4.Minimum of 2 joint bleeds (in haemarthroses of ankles, knees, or elbows) requiring haemostatic drug treatment within the previous 6 months, or at least 4 joint bleeds (haemarthroses of ankles, knees, or elbows) requiring haemostatic drug treatment within the previous 12 months at trial entry. 5.Subject has adequate venous access at screening visit as judged by the Investigator 6.The subject or caregiver is capable of assessing the bleed
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E.4 | Principal exclusion criteria |
1.Known allergy to rFVIIa, and/or suspected allergy to trial product 2.Subject is currently participating in another investigational drug study or has participated in any clinical study involving an investigational drug within 30 days of trial enrolment 3.Any known congenital or acquired coagulation disorder other than congenital haemophilia 4.Platelet count < 50,000/mm3 based on medical records at trial entry (visit 1)* 5.Any clinical signs or history of thromboembolic events 6.Advanced atherosclerotic disease 7.Severe liver disease (ALAT > 2 times the upper limit of normal reference range) based on medical records at trial entry. 8.Known active pseudo tumours (documented bleeding requiring treatment within the last 3 months) 9.Presence of any life- or limb-threatening bleeding episode, as judged by the Investigator 10.Planned surgery within 9 months after enrolment in this trial 11.Subject had any (major) surgical procedure in the 30 days prior to screening into the trial a.Catheter, ports and dental extractions do not count as surgeries and will not exclude the subject 12.Any disease or condition which, judged by the Investigator, could impose a potential hazard to the subject, interfere with the trial participation or trial outcome 13.Previous participation in this trial (screened and randomised to more than five NN1731 dose tier groups)
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E.5 End points |
E.5.1 | Primary end point(s) |
•Adverse events -Non-serious adverse events occurring from the first administration of trial product until 7 days after first trial product administration. -Serious adverse events are collected from the first administration of trial product to the end of subjects’ participation in the trial. Clinical symptoms associated with the joint bleeds are evaluated as efficacy parameters and should not be recorded as adverse events unless the subject or the Investigator believes it should be considered as an adverse event.
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | No |
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 | Yes |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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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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 | |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial days | 8 |