E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018937 |
E.1.2 | Term | Haemophilia A |
E.1.2 | System Organ Class | 100000004850 |
|
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 haemostatic effect of N8-GP during surgical procedures in patients with
haemophilia A |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the general safety including immunogenicity of N8-GP when used for prevention and treatment of bleeding throughout the surgical period
- To evaluate the haemostatic effect of N8-GP during the post-operative period
- To evaluate health economic resource use (hospitalisation days) due to surgery |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 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.)
- Ongoing participation in the pathfinderTM 2 (NN7088-3859) trial and having received ≥5 doses of N8-GP
- Undergoing major surgery (refer to Section 5.3.1 for definition) requiring daily monitoring of FVIII:C and wound status for ≥3 days
- The patient and/or Legally Acceptable Representative (LAR) is capable of assessing a bleeding episode, keeping an eDiary, capable of home treatment of bleeding episodes and otherwise capable of following the trial procedures |
|
E.4 | Principal exclusion criteria |
- Known or suspected hypersensitivity to trial product including allergy to hamster protein or related products
- Previous withdrawal from the pathfinderTM 2 (NN7088-3859) trial after administration of trial product, except interruption due to inclusion in this pathfinderTM 3 trial (NN7088-3860)
- The receipt of any investigational medicinal product (except N8-GP) within 30 days prior to enrolment into the trial. (For Brazil, only: Participation in a previous clinical trial within one year prior to screening for this trial (Visit 1), unless there is a direct benefit to the research subject, at the Investigator’s discretion)
- FVIII inhibitors ≥ 0.6 BU/mL at screening (refer to Section 8.1.1)
- Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records)
- Immune modulating or chemotherapeutic medication
- Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator’s judgement, could imply a potential hazard to the patient, interfere with trial participation or trial outcome
- Unwillingness, language or other barriers precluding adequate understanding and/or cooperation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Haemostatic effect during surgery evaluated by the four-point scale, assessed by the Investigator/surgeon at the day of surgery
- Four-point response scale: excellent, good, moderate or none |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Average consumption of N8-GP during surgery
- Haemostatic effect of N8-GP during the post-operative period Days 1-6 and 7-14
- Average consumption of N8-GP during the post-operative period Days 1-6
- Incidence rate of inhibitors against factor VIII (FVIII) (≥0.6 BU/mL) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be analysed based on all available information until End of Trial (EOT) Visit and up to approximately 5 weeks for each patient. |
|
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 | No |
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
| 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 | 30 |
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 |
Denmark |
France |
Italy |
Japan |
Croatia |
Netherlands |
Norway |
Sweden |
Australia |
Brazil |
Germany |
Hungary |
Korea, Republic of |
Malaysia |
Spain |
Israel |
Russian Federation |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |