A Multi-Centre, Open-Label, Non-Controlled Trial on Safety and Efficacy of N8 in Prevention and Treatment of Bleeds in Previously Treated Subjects withHaemophilia ASub-Trial:Safety and Efficacy of N8 in Prevention and Treatment of Bleeding during Surgical Procedures in Subjects with Haemophilia A
- Conditions
- Haemophilia AMedDRA version: 9.1Level: LLTClassification code 10018937Term: Haemophilia A
- Registration Number
- EUCTR2008-003960-20-DK
- Lead Sponsor
- ovo Nordisk A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 140
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 (FVIII=1%) haemophilia A from age 12 (except for Israel where the age limit will be 18 for the first 10 subjects recruited in the trial ) to 56 years having a weight of 10 to 120 kg.
4. Willing to undergo a bleeding preventative treatment of 75 dose 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 treatment of bleeds) (Please refer to section 8.6.2.3)
7. No history of FVIII inhibitors =0.6 BU/mL. The inhibitor should be measured regularly for at least the last 8 years or since the first treatment of haemophilia A (Please refer to section 8.6.2.2)
8. No detectable inhibitors to FVIII (=0.6 BU/mL) (as assessed by a Central Laboratory at the time of screening)
9. Not in use
10. Not in use
11. HIV-1 seronegative or if HIV-1 seropositive, viral load < 400.000 copies/mL and CD4+ lymphocyte count =200/µL.
Subjects who have completed NN7008-3522 have already met inclusion criteria no 1-3 and 5-11 in NN7008-3522.
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 (FVIII=1%) haemophilia A from age 12 (except for Israel where the age limit will be 18 for the first 10 subjects recruited in the trial and 18 for all subjects in Croatia) to 65 years having a weight of 10 (20 in Brazil) to 120 kg.
3. Willing to undergo a bleeding preventative treatment of 75 dose 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 (please refer to section 8.2.2)
5. Documented history of at least 150 exposure days to any other FVIII products (prevention or treatment of bleeds) (Please refer to section 8.6.2.3)
6. No prior history of FVIII inhibitors. Documentation should be available for at least the last 8 years (or since treatment with FVIII products started if shorter than 8 years), please refer to Section 8.6.2.2)for required documentation
7. No detectable inhibitors to FVIII (=0.6 BU/mL) (as assessed by a Central Laboratory at the time of screening)
8. Not in use
9. Not in use
10. HIV-1 seronegative or if HIV-1 seropositive, HIV viral load < 400.000 copies/mL and CD4+ lymphocyte count =200/µL.
Eligibility Criteria for Part C
1. Undergo major or minor surgical procedures (Please refer to section 8.2.8)
2. Surgical procedure requiring at least 7 days of infusion of N8 post-operatively
Subjects will only participate in Part C when they have been included in either Part A or Part B and have received at least one dose of trial product (N8). Subjects can be recruited into part C when at least 5 subjects have each been treated with N8 for a bleeding episode and 80% of these subjects have a response rated excellent or good on the four–point haemostatic response scale for their first bleeding epi
Exclusion Criteria for Part A and Part B
1. Subjects receiving Immune modulating medication or Tolerance Induction (ITI) regimens
2. Factor replacement treatment of a mild or moderate bleeding episode within 3 days prior to first dose (only applicable for subjects in Part B)
3. Factor replacement treatment of a severe bleeding episode within one week prior to first dose (only applicable for subjects in Part B)
4. Known pseudo-tumours
5. Platelet count <50,000 platelets/µL based on medical records and/or based on local laboratory values at trial entry
6. Severe current hepatic dysfunction or severe hepatic disease during the last 12 months
7. ALT > 4 times the upper limit of normal reference range (as defined by central laboratory ranges) (only for subjects in Part A)
8. Febrile illness within 5 days prior to the first trial product administration and PK dosing
9. Current dialysis therapy
10. Creatinine levels 50% above normal level (as defined by 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 other than N8: Commercial FVIII concentrates or other FVIII containing products within 48 hours prior to first administration of trial product for recovery assessment. (not applicable for Part A subjects 1-3)
16. Use of Anticoagulants: Heparin, vitamin-K antagonists, and direct thrombin inhibitors one week prior to first administration of trial product
17. Not in use
18. Not in use
19. Use of platelet inhibitors including NSAID one week prior to first administration of trial product (only for subjects in Part A)
20. The receipt of any investigational drug within 30 days prior to administration of trial product except subjects who have completed NN7008-3522 (for Brazil within one year prior to screening for this trial, unless there, in the investigators opinion, is a direct benefit to the research subject)
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method