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
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study 2. Male or female participants with diagnosis of congenital haemophilia A of any severity based on medical records 3. Participants has been prescribed treatment with factor VIII concentrates or bypassing agent in the last 26 weeks prior to screening 4. Age above or equal to 12 years at the time of signing informed consent. 5. Body weight greater than or equal to 30 kg 6. Applicable to participants treated with on-demand/no prophylaxis prior to enrolment: =5 bleeds in the last 26 weeks prior to screening visit, for which factor VIII concentrates or bypassing agent has been prescribed 7. Applicable to participants with FVIII activity greater than or equal to 1% who are on prophylactic treatment: greater than or equal to 1 bleed in the last 26 weeks prior to screening visit, for which factor VIII concentrates or bypassing agent has been prescribed 8. Willingness and ability to comply with scheduled visits and study procedures, including the completion of diary and patient-reported outcomes questionnaires Are the trial subjects under 18? yes Number of subjects for this age range: 69 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 168 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Previous participation in this study. Participation is defined as signed informed consent 2. Participation (i.e., signed informed consent) in any interventional clinical study with receipt of the last dose within 6 months (or 5 half-lives of the investigational medicinal product, whichever is shorter) before planned randomisation. 3. Exposure to non-factor haemostatic products for bleeding prophylaxis within 6 months (or 5 half-lives of the medicinal product, whichever is shorter) before planned randomisation, for participants not included in the run-in. 4. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method (highly effective contraceptive measures as defined in Section ?10.4 or as required by local regulation or practice). Breast feeding is allowed only during the run-in period. 5. Any disorder, except for conditions associated with haemophilia A, which in the investigator’s opinion might jeopardise participant’s safety or compliance with the protocol. 6. Known or suspected hypersensitivity to trial product(s), any constituents of the product or to related products. 7. Receipt of gene therapy at any given time point. 8. Ongoing or planned immune tolerance induction (ITI) therapy. 9. Major surgery planned to take place after screening. 10. Known congenital or acquired coagulation disorders other than haemophilia A. 11. Hepatic dysfunction defined as AST and/or ALT greater than 3 times the upper limit combined with total bilirubin greater than 1.5 times the upper limit measured at screening. 12. Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) less than or equal to 30 ml/min/1.73 m2 for serum creatinine measured at screening. 13. Previous or current thromboembolic disease or events (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or risk of thromboembolic disease, as evaluated by investigator. 14. Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation. 15. Other conditions (e.g., autoimmune disease) or laboratory abnormality that may increase risk of bleeding or thrombosis as evaluated by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To confirm the haemostatic effect of Mim8 as bleeding prophylaxis for adults and adolescents with haemophilia A with or without inhibitors. This will be done by: • Demonstrating superiority in number of bleeding episodes when treated with Mim8 once-weekly versus no prophylaxis for participants on no prophylaxis treatment prior to enrolment (Comparing Arm 1 and Arm 2 main treatment period) • Demonstrating non-inferiority in number of bleeding episodes when treated with either Mim8 once-weekly or once-monthly versus treatment with coagulation factor prophylaxis during run-in for participants on prophylaxis treatment prior to enrolment (Comparing Arm 3 and Arm 4 run-in with main treatment period).;Secondary Objective: 1. To investigate safety of Mim8 prophylaxis in adults and adolescents with haemophilia A with or without FVIII inhibitors. 2. To evaluate the consumption of factor product per bleed treatment (number of injections) after Mim8 prophylaxis in adults and adolescents with haemophilia A with or without inhibitors. 3. To evaluate the development of anti-Mim8 antibodies after Mim8 prophylaxis in adults and adolescents with haemophilia A with or without inhibitors. 4. To evaluate treatment burden after Mim8 prophylaxis in adults and adolescents with haemophilia A with or without inhibitors. 5. To evaluate aspects of patient’s physical functioning after Mim8 prophylaxis in adults and adolescents with haemophilia A with or without inhibitors. 6. To evaluate joint pain intensity after Mim8 prophylaxis in adults and adolescents with haemophilia A with or without inhibitors.;Primary end point(s): Number of treated bleeds;Timepoint(s) of evaluation of this end point: - No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (week 26) - Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from randomisation (week 0) to end of main (week 26) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of injection site reactions 2. Occurrence of antiMim8 antibodies 3. Number of treated spontaneous bleeds 4. Number of treated joint bleeds 5. Number of treated traumatic bleeds 6. Number of treated target joint bleeds 7. Consumption of factor product per bleed treatment (number of injections) 8. Change in physical function domain of paediatric quality of life inventory (PEDS-QL) 9. Change in participant’s treatment burden using the haemophilia treatment experience measure (Hemo-TEM) 10. Change in participant’s joint pain score using Joint Pain Rating Scale;Timepoint(s) of evaluation of this end point: 1. All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of main (week 26) 2. All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of extension (week 52) 3. – 7.: - No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (week 26) - Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from randomisation (week 0) to end of main (week 26) 8. – 10.: All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26) | — |
Countries
Austria, Belgium, Canada, China, Denmark, European Union, France, Germany, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Netherlands, Poland, Portugal, Russian Federation, Saudi Arabia, Serbia, Slovakia, South Africa, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Transparency (2834)
Novo Nordisk A/S
Outcome results
None listed