A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER 4)

Study Overview
=================
Brief Summary
-----------------
This study is looking at how Mim8 works in people with haemophilia A, who either have inhibitors or do not have inhibitors. Mim8 is a new medicine that will be used to avoid bleeding episodes. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). When and how often the participants will receive Mim8 in this study depends on the treatment participant receives in the current Mim8 study participant is taking part in. The study will last for up to 5.5 years. The duration of the study depends on when the participant enrolled in this study. The study will end if Mim8 is approved and marketed in participant's country during the study, or the study will end in 2028, whichever comes first. Mim8 will be injected under the skin with a thin needle either once a week, once every two weeks or once a month. Participants will get up to 262 injections; the number of injections depends on how often participants will get injections. While taking part in this study, there are some restrictions about what medicine participants can use. The study doctor will tell the participants more about this. In case the participants experience bleeds, these can be treated with additional haemostatic medicine as agreed with the study doctor. Female participants cannot take part if they are pregnant, breast-feeding or plan to get pregnant during the study period.

Official Title
-----------------
Open-label, Long-term Safety and Efficacy Study of Mim8 in Participants With Haemophilia A With or Without Inhibitors

Conditions
-----------------
Haemophilia A, Haemophilia A With Inhibitors

Intervention / Treatment
-----------------
* Drug: Mim8


Participation Criteria
=================
Eligibility 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 with diagnosis of congenital haemophilia A based on medical records Ongoing participation in study NN7769-4513, NN7769-4514, NN7769-4516, or NN7769-4728 at the time of transfer. Participant should qualify either of the following criteria: Participant from study NN7769-4513, who has participated in the extension part of the study for at least 12 weeks prior to enrolment in study NN7769-4532, or, Participant has completed the end of treatment visit for study NN7769-4514, NN7769-4516 or NN7769-4728. Participant and/or participant's parent(s)/participant's Legally acceptable representative (LAR) willingness and ability to comply with scheduled visits and study procedures, including the completion of diary. Exclusion Criteria: Any disorder, except for conditions associated with haemophilia, which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol. Participant who has discontinued or been withdrawn from studies NN7769-4513, NN7769-4514, NN7769-4516, or NN7769-4728. Previous participation in this study. Participation is defined as signed informed consent. Female who is pregnant, breast-feeding or intends to become pregnant. Female of child-bearing potential and not using a highly effective contraceptive method (highly effective contraceptive measures or as required by local regulation or practice). Participation (i.e., signed informed consent) in any interventional, clinical study (except from study NN7769-4513, NN7769-4514, NN7769-4516, or NN7769-4728) of an approved or non-approved investigational medicinal product. Any planned major surgery, during part 1 of the study. Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation.

Ages Eligible for Study
-----------------
Minimum Age: 1 Year

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Participants entering from the multiple ascending dose (MAD) part of study NN7769-4513. In part 1, participants will receive Mim8 prophylaxis (PPX) once every two weeks (Q2W) with subcutaneous (s.c.) administration using enhanced cartridge for 26 weeks. In part 2, participants will receive Mim8 PPX once-weekly (QW), Q2W or once-monthly (QM) with s.c. administration using enhanced cartridge or DV3407 pen-injector once it is approved. | Drug: Mim8<br>* Participants in arm 1 will administer Mim8 using an enhanced cartridge and switch to the DV3407 pen-injector once it is approved. Participants in arm 2 will use the DV3407 pen injector.<br>|
| Experimental: Arm 2<br>Participants entering from study NN7769-4514 or NN7769-4516. In part 1, participants will receive Mim8 PPX QW or QM with s.c. administration using DV3407 pen-injector for 26 weeks. In part 2, participants will receive Mim8 PPX QW, Q2W or QM with s.c. administration using DV3407 pen-injector. | Drug: Mim8<br>* Participants in arm 1 will administer Mim8 using an enhanced cartridge and switch to the DV3407 pen-injector once it is approved. Participants in arm 2 will use the DV3407 pen injector.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment emergent adverse events | Measured as count of events. | From visit 1 (week 0) until end of study (up to 283 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of injection site reactions | Measured as count of reactions. | From visit 1 (week 0) until end of treatment (up to 262 weeks) | 
| Occurrence of anti Mim8 antibodies | Measured as count of participants. | From visit 1 (week 0) until end of treatment (up to 262 weeks) | 
| Number of treated bleeding episodes | Measured as count of bleeds. | From visit 1 (week 0) until end of treatment (up to 262 weeks) | 
| Number of treated spontaneous bleeding episodes | Measured as count of bleeds. | From visit 1 (week 0) until end of treatment (up to 262 weeks) | 
| Number of treated traumatic bleeding episodes | Measured as count of bleeds. | From visit 1 (week 0) until end of treatment (up to 262 weeks) | 
| Number of treated joint bleeding episodes | Measured as count of bleeds. | From visit 1 (week 0) until end of treatment (up to 262 weeks) | 
| Number of treated target joint bleeding episodes (arm 2) | Measured as count of bleeds. | From visit 1 (week 0) until end of treatment (up to 262 weeks) | 
| Mim8 plasma concentration | Measured as micrograms per milliliter (µg/mL). | From visit 1 (week 0) until end of treatment (up to 262 weeks) | 
| Device handling using haemophilia device assessment tool (HDAT) (applicable for participants in arm 2 only) | Measured as percentage of participants. | From visit 8 (week 26) until end of treatment (up to 262 weeks) |