Healthy volunteers (Haemophilia A with or without inhibitors) Haemophilia A Haemophilia A with inhibitors MedDRA version: 20.0 Level: LLT Classification code 10018938 Term: Haemophilia A (Factor VIII) System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 100000004850
Conditions
Interventions
Product Name: NNC0365-3769 A 10 mg/mL
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
CAS Number: *MASKED*
Current Sponsor code: NNC0365-3769
Other descriptive name: NNC0365-3769
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Single ascending dose (SAD) part: - Male, aged 18-45 years (both inclusive) at the time of signing informed consent - Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator Multiple ascending dose (MAD) part: - Male, aged 12-64 years (both inclusive) at the time of signing informed consent (Germany and Japan have local requirements) - Diagnosis of congenital haemophilia A with FVIII activity =65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: SAD part: - Factor VIII activity =150% at screening - Increased risk of thrombosis, e.g. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis - Any clinical signs or established diagnosis of venous or arterial thromboembolic disease MAD part: - Known congenital or acquired coagulation disorders other than haemophilia A - Increased risk of thrombosis as evaluated by the investigator. E.G. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing - Any clinical signs or established diagnosis of venous or arterial thromboembolic disease with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing - Advanced atherosclerotic disease (e.g. known history of ischemic heart disease, ischemic stroke) as evaluated by the investigator - Any autoimmune disease that may increase the risk of thrombosis - Receipt of emicizumab or drugs with similar modes of action within 5 half-lives before trial product administration - Ongoing or planned immune tolerance induction therapy Exploratory biomarker cohort: - Known congenital or acquired coagulation disorders other than haemophilia A - Increased risk of thrombosis as evaluated by the investigator, e.g. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing - Any clinical signs or established diagnosis of venous or arterial thromboembolic disease with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing - Advanced atherosclerotic disease (e.g. known history of ischemic heart disease, ischemic stroke) as evaluated by the investigator - Any autoimmune disease that may increase the risk of thrombosis - Ongoing or planned immune tolerance induction therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and tolerability of subcutaneous Mim8 in healthy subjects and in subjects with severe haemophilia A with or without FVIII inhibitors;Secondary Objective: 1. To investigate the pharmacokinetics of subcutaneous Mim8 in healthy subjects and in subjects with severe haemophilia A with or without FVIII inhibitors 2. To investigate the pharmacodynamics of subcutaneous Mim8 in healthy subjects and in subjects with severe haemophilia A with or without FVIII inhibitors;Primary end point(s): 1. Single ascending dose (SAD) part: Number of treatment emergent adverse events 2. Multiple ascending dose (MAD) part: Number of treatment emergent adverse events 3. Extensíon to the MAD part: Number of treatment emergent adverse events;Timepoint(s) of evaluation of this end point: 1. From time of dosing (Day 1) to Week 16 2. From time of first dosing (Day 1) to Week 12 3. From Week 12 up to Week 120 (16 weeks after last dose) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SAD part: 1. Number of injection site reactions 2. Relative change in D-dimer 3. Relative change in prothrombin fragment 1 and 2 4. Relative change in fibrinogen 5. Relative change in platelets 6. Cmax, SD: the maximum concentration of Mim8 after a single dose 7. AUC0-inf, SD: the area under the Mim8 concentration-time curve from time 0 to infinity after a single dose 8. t1/2, SD: the terminal half-life of Mim8 after a single dose 9. tmax, SD: the time to maximum concentration of Mim8 after a single dose 10. Change in activated partial thromboplastin time MAD part (weekly and monthly dosing): 11. Number of injection site reactions 12. Occurrence of anti-Mim8 antibodies 13. Relative change in D-dimer 14. Relative change in prothrombin fragment 1 and 2 15. Relative change in fibrinogen 16. Relative change in platelets MAD part, PK session 2 (weekly dosing): 17. Cmax, MD: the maximum concentration of Mim8 after multiple doses 18. AUCt, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses MAD part, PK session 2 (monthly dosing): 19. Cmax, MD: the maximum concentration of Mim8 after multiple doses 20. AUCt, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses MAD part (weekly dosing): 21. Mean of maximum thrombin generation (peak height) MAD part (monthly dosing): 22. Mean of maximum thrombin generation (peak height) Extension to the MAD part: 23. Number of injection site reactions 24. Occurrence of anti-Mim8 antibodies;Timepoint(s) of evaluation of this end point: 1. From time of dosing (Day 1) to Week 16 2-10. From baseline (Day 1) to Week 16 11. From time of first dosing (Day 1) to Week 12 12-16. From baseline (Day 1) to Week 12 17-18. From Day 57 to Day 64 19-20. From Day 57 to Day 85 21. From Day 57 to Day 64 22. From Day 57 to Day 85 23-24. From Week 12 up to Week 120 (16 weeks after last dose) | — |
Countries
Austria, Bulgaria, European Union, Germany, Italy, Japan, Poland, Serbia, South Africa, Spain, Switzerland, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Transparency (1452)
Novo Nordisk A/S
Outcome results
None listed