Health Condition 1: D66- Hereditary factor VIII deficiency
Conditions
Interventions
Intervention1: NNC0365-3769 (Mim8): Dose: TF or a once-weekly dose interval, including the loading dose, the anticipated dose will be within the
range 10–75 mg and for the maintenance dose, within the
Sponsors
Novo Nordisk AS
Eligibility
Inclusion criteria
Inclusion criteria: • 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. • Male or female participants with diagnosis of congenital haemophilia A of any severity based on medical records. • Participant has been prescribed treatment with factor VIII concentrates or bypassing agent in the last 26 weeks prior to screening. • Age above or equal to 12 years at the time of signing informed consent. • Body weight greater than or equal to 30 kg. • 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. • Applicable to participants with FVIII activity =1% who are on prophylactic treatment: =1 bleed in the last 26 weeks prior to screening visit, for which factor VIII concentrates or bypassing agent has been prescribed. • Willingness and ability to comply with scheduled visits and study procedures, including the completion of diary and patient-reported outcomes questionnaires.
Exclusion criteria
Exclusion criteria: 1. Previous participation in this study. Participation is defined as signed informed consent. 2. Participation (that is, 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 hemostatic 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. Breast feeding is allowed only during the run-in period. 5. Any disorder, except for conditions associated with hemophilia A, which in the investigators opinion might jeopardise participants 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 hemophilia A. 11. Hepatic dysfunction defined as aspartate aminotransferase (AST) and or alanine aminotransferase (ALT) above 3 times the upper limit combined with total bilirubin above 1.5 times the upper limit measured at screening. 12. Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below or equal to 30 ml per min per 1.73 meter square 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. Other conditions (example, autoimmune disease) or laboratory abnormality that may increase risk of bleeding or thrombosis as evaluated by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To confirm the haemostatic effect of Mim8 as bleeding prophylaxis for adults and adolescents with haemophilia A with or without inhibitors by demonstrating superiority in number of bleeding episodes when treated with Mim8 once-weekly versus no prophylaxis followed by Mim8 once-monthly versus no prophylaxis for participants on no prophylaxis treatment prior to enrolment. Unit: CountTimepoint: 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 |
|---|---|
| Occurrence of anti-Mim8 antibodiesTimepoint: All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of extension (week 52);Number of treated spontaneous bleedsTimepoint: 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 week 0 to end of main (week 26);Number of injection site reactionsTimepoint: All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of main (week 26);Number of treated joint bleedsTimepoint: 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 week 0 to end of main (week 26);Number of treated traumatic bleedsTimepoint: 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 week 0 to end of main (week 26);Number of target joint bleedsTimepoint: 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 week 0 to end of main (week 26);Consumption of factor product per bleed treatment (number of injections)Timepoint: 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 week 0 to end of main (week 26);Change in physical function domain of PEDS-QLTimepoint: All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26) Score points Minimum score per question (be | — |
Countries
Austria, Belgium, Canada, China, Denmark, France, Germany, India, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Poland, Portugal, Republic of Korea, Romania, Russian Federation, Saudi Arabia, Serbia, South Africa, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactDr Maya Sharma
Novo Nordisk India Pvt Ltd
Outcome results
None listed