A Research Study Looking at Mim8 in Children With Haemophilia A With or Without Inhibitors

Study Overview
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Brief Summary
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This study is looking at how Mim8 works compared to other medicines in children with haemophilia A, who either have inhibitors or do not have inhibitors. Mim8 is a new medicine that will be used for prevention of bleeds. Mim8 will be injected with a thin needle into the skin. The study will last for about 54-98 weeks, from screening to follow-up visit, In case the participant experiences bleeds, these can be treated with additional haemostatic medicine as agreed with the study doctor.

Official Title
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Safety, Efficacy and Exposure of Subcutaneously Administered NNC0365-3769 (Mim8) Prophylaxis in Children With Haemophilia A With or Without FVIII Inhibitors

Conditions
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Haemophilia A With or Without Inhibitors

Intervention / Treatment
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* Drug: 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 and female participants with the diagnosis of congenital haemophilia A of any severity based on medical records. Aged 1-11 years (both inclusive) at the time of signing informed consent. For previously treated participants : Participant has been prescribed treatment with FVIII concentrate or bypassing agent in the last 26 weeks prior to screening. Participants with endogenous FVIII activity greater than or equal to 1%, based on medical records, must have at least 1 treated bleed during the previous 26 weeks before screening for which factor VIII concentrate or bypassing agent has been prescribed (no requirements for participants with FVIII activity below 1%). For previously untreated participants: a. Diagnosis of severe haemophilia A (endogenous FVIII activity below 1%) based on medical records. Child and parent/caregiver willingness and ability to comply with scheduled visits and study procedures, including the completion of diary and patient-reported outcomes questionnaires.( For China mainland; assessed at the investigator's discretion unless otherwise stated.) Exclusion criteria: Known or suspected hypersensitivity to trial product or related products.(For China mainland; assessed at the investigator's discretion unless otherwise stated.) 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 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. Known congenital or acquired coagulation disorders other than haemophilia A. Other conditions (e.g. autoimmune disease) or laboratory abnormality that may increase risk of bleeding or thrombosis, as evaluated by the investigator.(For China mainland; assessed at the investigator's discretion unless otherwise stated.) Any disorder, except for conditions associated with haemophilia A, that in the investigator's opinion might jeopardise the participant's safety or compliance with the protocol.(For China mainland; assessed at the investigator's discretion unless otherwise stated.) Mental incapacity, unwillingness to cooperate or a language barrier precluding adequate understanding and cooperation.(For China mainland; assessed at the investigator's discretion unless otherwise stated.) Lack of adequate parental/caregiver support to enter accurately and timely information regarding treatment and bleeding episodes into an (electronic) diary.(For China mainland; assessed at the investigator's discretion unless otherwise stated.) Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease. Major surgery planned to take place after screening.(For China mainland; assessed at the investigator's discretion unless otherwise stated.) Immune tolerance induction planned to take place after treatment initiation.(For China mainland; assessed at the investigator's discretion unless otherwise stated.) Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than 3 times the upper limit of normal combined with total bilirubin greater than 1.5 times the upper limit of normal measured at screening. Serum creatinine above 1.5 x upper limit of normal (ULN), measured at screening. Pregnancy (female participants).(Will be assessed at investigator's discretion, according to suspicion of pregnancy.)

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 11 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mim8<br>52-week treatment period with a part 1 and part 2, where all participants receive Mim8 prophylaxis | Drug: Mim8<br>* For treatment part 1, all participants will start on once-weekly treatment and continue on this regimen until week 26. For treatment part 2, starting at week 26, all participants will be offered the choice to remain on once-weekly or switch to once-monthly dosing. Mim8 will be injected with a thin needle into the skin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment emergent adverse events | Count of events | From treatment initiation to follow up visit (week 0 to week 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treated bleeds | Count of bleeds | From treatment initiation to end of treatment (week 0 to week 52) | 
| Number of treated spontaneous bleeds | Count of bleeds | From treatment initiation to end of treatment (week 0 to week 52) | 
| Number of treated traumatic bleeds | Count of bleeds | From treatment initiation to end of treatment (week 0 to week 52) | 
| Number of treated joint bleeds | Count of bleeds | From treatment initiation to end of treatment (week 0 to week 52) | 
| Number of treated target joint bleeds | Count of bleeds | From treatment initiation to end of treatment (week 0 to week 52) | 
| Number of injection site reactions | Count of reactions | From treatment initiation to end of treatment (week 0 to week 52) | 
| Consumption of factor product per bleed treatment (number of injections) | Count of injections | From run-in initiation to end of treatment (week -26 to week 52) | 
| Occurrence of anti-Mim8 antibodies | Count of participants | From treatment initiation to end of treatment (week 0 to week 52) | 
| Mim8 plasma concentration | µg/mL | From treatment initiation to end of treatment (week 0 to week 52) | 
| Change in physical function domain of PEDS QL (Paediatric Quality of Life inventory) Generic Core Scales | Score on a scale 0-100 (applies for scale scores and total score). A higher score indicates a better health-related quality of life | From treatment initiation to end of treatment (week 0 to week 52) | 
| Treatment preference for Mim8 versus previous treatment using Caregiver H PPQ (Caregiver Haemophilia Patient Preference ) | Percentage of participants | Once during treatment (week 26) | 
| Change in participants' treatment burden using the Hemo TEM (Haemophilia treatment experience measure) | Score on a scale 0-100 (applies for scale scores and total score). A lower score indicates a lower treatment burden. | From treatment initiation to end of treatment (week 0 to week 52) |