Ensayo multicéntrico, abierto, no controlado sobre la eficacia y la seguridad de N8 en la prevención y el tratamiento a demanda de los episodios hemorrágicos en sujetos con hemofilia A previamente tratadosSubestudio:Eficacia y seguridad de N8 en la prevención y el tratamiento de la hemorragia durante los procedimientos quirúrgicos en sujetos con hemofilia AEfficacy and Safety of N8 in Prevention and On-demandTreatment of Bleeding Episodes in Previously TreatedSubjects with Haemophilia ASub-Trial:Efficacy and Safety of N8 in Prevention and Treatmentof Bleeding during Surgical Procedures in Subjects withHaemophilia A

Conditions: Haemophilia AHemofilia A
MedDRA version: 9.1Level: LLTClassification code 10018937Term: Haemophilia A

Registration Number: EUCTR2008-003960-20-ES

Lead Sponsor: ovo Nordisk A/S

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 140

Inclusion Criteria

Part A
1. Completion of the phase 1 PK trial NN7008-3522
2. Informed consent obtained prior to any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
3. Male subjects with the diagnosis of severe (baseline FVIII?1%) haemophilia A from age 12 to 56 years having a weight of 10 to 120 kg.
4. Willing to undergo a bleeding preventive regimen of 75 exposure days
5. Non-bleeding state (i.e. no clinical manifestation of active bleed) at the time of administration of trial product for measurement of recovery in relation to administration of the first dose and the PK session
6. Documented history of at least 150 exposure days to any other FVIII products (prevention or on-demand treatment) (Please refer to section 8.6.2.3)
7. No history of FVIII inhibitors ?0.6 BU/mL measured regularly since the first treatment of haemophilia A prior to entering the trial or the time period should cover at least 8 years (Please refer to section 8.6.2.2)
8. No detectable inhibitors to FVIII ( ?0.6 BU/mL) (as assessed by central laboratory at the investigative site at the time of screening)
9. Hepatitis C Virus (HCV) seronegative or if HCV seropositive, viral load <200.000 IU/mL and CD4+ lymphocyte count ? 200/µL.
10. Lupus anticoagulant negative
11. HIV-1 seronegative or if HIV-1 seropositive, the viral load <400.000 copies/mL and the CD4+ lymphocyte count ?200/µL.
Part B
1. Informed consent obtained prior to any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the subject).
2.Male subjects with the diagnosis of severe (baseline FVIII?1%) haemophilia A from age 12 to 65 years having a weight of 10 to 120 kg.
3. Willing to undergo a bleeding preventive regimen of 75 exposure days 4. Non-bleeding state (i.e. no clinical manifestation of active bleed) at the time of administration of trial product for measurement of recovery in relation to administration of the first dose
5. Documented history of at least 150 exposure days to any other FVIII products (prevention or on-demand treatment) (Please refer to section 8.6.2.3)
6. No history of FVIII inhibitors ?0.6 BU/mL measured regularly since the first treatment of haemophilia A prior to entering the trial or the time period should cover at least 8 years (Please refer to History of Inhibitors in section 8.6.2.2)
7. No detectable inhibitors to FVIII ( ?0.6 BU/mL) (as assessed by central laboratory at the time of screening)
8. HCV seronegative and or if HCV seropositive, viral load <200.000 IU/mL and CD4+ lymphocyte count ? 200/µL.
9. Lupus anticoagulant negative
10. HIV-1 seronegative or if HIV-1 seropositive, the viral load <400.000
copies/mL and the CD4+ lymphocyte count ?200/µL.
Part C:
12.Scheduled to undergo major or minor surgical procedures
13.Surgical procedure requiring at least 6 days of infusion of N8 concentrate post-operatively.
Subjects will only participate in Part C when they have been included in either Part A or Part and have received at least one dose of trial product (N8).
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects on Immune Tolerance Treatment (ITT) regimens
2.Pharmaceutical treatment of a mild and moderate bleeding episode within one week prior to first dose
3. Pharmaceutical treatment of a severe bleeding episode within one week prior to first dose
4. Known pseudo-tumours
5. Platelet count <50,000 platelets/µL (based on medical records) at trial entry
6. Severe current hepatic dysfunction or severe hepatic disease during the last 12 months
7. ALAT > than 4 times of the upper limit of normal reference range (as defined by central laboratory ranges
8. Septicaemia, e.g. febrile illness within 5 days prior to trial product administration
9. Current dialysis therapy
10. Creatinine levels 50% above normal level (according to central laboratory range)
11. Congenital or acquired coagulation disorders other than haemophilia A
12. Previous arterial thrombotic events (Myocardial Infarction and Intra Cranial Thrombosis) (as defined by medical records).
13. Known or suspected allergy to trial product (N8) or related products
14. Surgery within one month prior to first administration of trial product (catheter, stents, ports, and dental extractions do not count as surgeries, i.e. they will not exclude the subject)
15. Use of Coagulation Factors: FVIII concentrates or other FVIII containing products within four days prior to first administration of trial product
16. Use of Anticoagulants: Heparin, vitamin-K antagonists, and direct thrombin inhibitors one week prior to first administration of trial product
17. Use of non-prescribed opiate substances
18. Regular use of cannabis (only for subjects in Part A)
19. Use of platelet inhibitors including NSAID one week prior to first administration of trial product
20. The receipt of any investigational drug within 30 days prior to administration of trial product except subjects who have completed NN7008-3522
21. Previous participation in the current trial (defined as withdrawal) or withdrawn subjects from NN7008-3522 after administration of trial product
22. Any disease or condition which, according to the Investigator?s judgement, could imply a potential hazard to the subject, interfere with the trial participation or trial outcome
23. Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation