A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors

Study Overview
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Brief Summary
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This study is investigating how Mim8 works compared to other medicines in people with haemophilia A, who either have inhibitors or do not have inhibitors. Mim8 is a new medicine that will be used for prevention of bleeding episodes. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). When and how often participants will receive Mim8 is dependent on their previous treatment - but is otherwise decided by chance. Mim8 will be injected into a skinfold on the stomach with a thin needle either once a week or once a month. The study will last 54-124 weeks (12-29 months) depending on how long participants will be followed in run-in before they start treatment and if they continue in the follow period or transfer to an open label extension study. Participants will have 12-17 clinic visits.

Official Title
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A Multinational, Open-label, Randomised, Controlled Study to Investigate Efficacy and Safety of NNC0365-3769 (Mim8) in Adults and Adolescents With Haemophilia A With or Without Inhibitors

Conditions
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Haemophilia A, Haemophilia A With Inhibitors

Intervention / Treatment
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* Drug: NNC0365-3769 (Mim8)


Participation Criteria
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Eligibility Criteria
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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: Previous participation in this study. Participation is defined as signed informed consent. 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. 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. 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. 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. Known or suspected hypersensitivity to trial product(s), any constituents of the product or to related products. Receipt of gene therapy at any given time point. Ongoing or planned immune tolerance induction (ITI) therapy. Major surgery planned to take place after screening. Known congenital or acquired coagulation disorders other than haemophilia A. Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above 3 times the upper limit combined with total bilirubin above1.5 times the upper limit measured at screening. Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below or equal to 30 ml/min/1.73 m^2 for serum creatinine measured at screening. 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. Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation. Other conditions (e.g., autoimmune disease) or laboratory abnormality that may increase risk of bleeding or thrombosis as evaluated by the investigator.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: no PPX- no PPX - Mim8 PPXQW/QM<br>Participants not receiving prophylaxis will not enter the run-in period. In arm 1, participants will be randomised to continue no prophylaxis (on-demand treatment with their Standard of Care products) or Mim8 once-weekly or once-monthly prophylaxis in agreement with investigators in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) in agreement with the investigator, either weekly or monthly Mim8 prophylaxis regimen. | Drug: NNC0365-3769 (Mim8)<br>* Mim8 will be injected into a skinfold on the stomach with a thin needle either once a week or once a month.<br>|
| Experimental: no PPX - Mim8 PPXQW - Mim8 PPXQW<br>Participants not receiving prophylaxis will not enter the run-in period. In arm 2a, participants will be randomised to Mim8 once-weekly prophylaxis in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) on once-weekly Mim8 prophylaxis regimen. | Drug: NNC0365-3769 (Mim8)<br>* Mim8 will be injected into a skinfold on the stomach with a thin needle either once a week or once a month.<br>|
| Experimental: no PPX - Mim8 PPXQM - Mim8 PPXQM<br>Participants not receiving prophylaxis will not enter the run-in period. In arm 2b, participants will be randomised to Mim8 once-monthly prophylaxis in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) on once-monthy Mim8 prophylaxis regimen. | Drug: NNC0365-3769 (Mim8)<br>* Mim8 will be injected into a skinfold on the stomach with a thin needle either once a week or once a month.<br>|
| Experimental: PPX - Mim8 PPXQW<br>Participants on coagulation factor prophylaxis prior to enrolment will preferably continue the same product type and dosing frequency in the run-in period for at least 26 weeks before they can be randomised into the main part of the study. These participants will only be allowed to receive coagulation factor prophylaxis. In arm 3, participants will be randomised to once-weekly Mim8 prophylaxis regimen in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) on once-weekly Mim8 prophylaxis regimen. | Drug: NNC0365-3769 (Mim8)<br>* Mim8 will be injected into a skinfold on the stomach with a thin needle either once a week or once a month.<br>|
| Experimental: PPX- Mim8 PPXQM<br>Participants on coagulation factor prophylaxis prior to enrolment will preferably continue the same product type and dosing frequency in the run-in period for at least 26 weeks before they can be randomised into the main part of the study. These participants will only be allowed to receive coagulation factor prophylaxis. In arm 4, participants will be randomised to once-monthly Mim8 prophylaxis regimen in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) on once-monthly Mim8 prophylaxis regimen. | Drug: NNC0365-3769 (Mim8)<br>* Mim8 will be injected into a skinfold on the stomach with a thin needle either once a week or once a month.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treated bleeds | Count | No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (week 26) | 
| Number of treated bleeds | Count | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of injection site reactions | Count | All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of main (week 26) | 
| Occurrence of anti-Mim8 antibodies | Count | All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of extension (week 52) | 
| Number of treated spontaneous bleeds | Count | 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 joint bleeds | Count | 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 bleeds | Count | 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 bleeds | Count | 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) | Count | 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-QL (pediatric quality of life inventory) | Score points Minimum score per question (best) = 0 Maximum score per question (worst) = 4 Total score for 13 questions: 0 (best) to 92 (worst) | All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26) | 
| Change in patient's treatment burden using the Hemo-TEM (haemophilia treatment experience measure) | Score points Ranges from 0 (best) - 4 (worst) representing answers ranging: 'Not at all difficult' - 'Extremely difficult' 'Never' - 'always' 'Not at all bothered' - 'Extremely bothered' 'Not at all interfering' - 'Extremely interfering' 'Not at all burdened' - 'Extremely burdened' | All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26) | 
| Change in patient's joint pain score using Joint Pain Rating Scale | Score points ranges from 0 = 'not at all' (best) to 4 = 'extremely' (worst) | All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26) |