1. Objective
1) Primary objective: To investigate long-term safety of Mim8 prophylaxis in participants with haemophilia A with or without FVIII inhibitors
2) Secondary objectives:
- To evaluate efficacy of Mim8 once every two weeks (Q2W) prophylaxis, and long-term efficacy of once-weekly (QW), Q2W and once-monthly (QM) prophylaxis, in participants with haemophilia A with or without inhibitors
- To evaluate the device handling experience for administration of Mim8 using the DV3407-C1 pen-injector.
3) Exploratory objective: To evaluate patient reported outcomes with Mim8 prophylaxis in participants with haemophilia A with or without FVIII inhibitors

2. Background
1) Nonclinical data: Mim8 has been evaluated in a nonclinical programme comprising pharmacokinetics (PK), toxicology, efficacy, and safety pharmacology. Based on the mode of action, the available information from the toxicology studies with Mim8, and the limited toxicological findings reported with emicizumab, the main potential safety risk with Mim8 is expected to be exaggerated stimulation of the coagulation cascade.
The haemostatic effect of Mim8 was confirmed both in vitro, and in vivo using bleeding models in cynomolgus monkeys and mice supplemented with human FIX and FX. Across pharmacological assays, Mim8 showed approximately 15-fold increased potency compared to a sequence identical analogue to emicizumab (emicizumab-SIA). 
2) Clical data: Study 4513, initiated in January 2020, is an ongoing phase 1/2 study, with the purpose to investigate the safety, tolerability, PK, and pharmacodynamics (PD) of single and multiple s.c. injections of Mim8 in healthy male participants (18−45 years of age; single ascending dose [SAD] part) and in adult and adolescent male participants (12−64 years of age; MAD part) with severe haemophilia A with or without FVIII inhibitors. Exploratory efficacy in terms of prevention of bleeding episodes during 12 weeks of treatment was also investigated in participants with severe haemophilia A with or without FVIII inhibitors.
3) Overall benefit-risk conclusion: Taking into account the findings from nonclinical and clinical studies and the measures taken to minimise risk and burden to participants included in this study, the potential risks identified with
Mim8 are justified by the anticipated benefits that may be afforded to participants with haemophilia A with or without FVIII inhibitors.

3. Study design
This is an interventional, prospective, multinational, multicentre, non-controlled, open-label phase 3b extension study. The study consists of two arms (Arms 1 and 2), where participants from the MAD part of study 4513 will enter Arm 1 and participants from studies 4514, 4516, and 4728 will enter Arm 2. The arms will open for enrolment at different timepoints to allow transfer of participants from the respective studies. Study 4532 will end in June 2028 or when Mim8 is commercially available in the respective participating countries, whichever comes first. Long-term safety and efficacy of Mim8 prophylaxis will be investigated in children (1−11 years of age), adolescents (12−17 years of age) and adults (≥18 years of age), in participants with haemophilia A with or without FVIII inhibitors. Participants with at least 12 weeks of Mim8 treatment in the extension part of study 4513, and participants completing studies 4514, 4516, or 4728 will be eligible. The study intervention consists of the investigational medicinal product, Mim8, which will be administered to all study participants in three different treatment frequencies: QW, Q2W and QM. Participants transferring from study NN7769-4513 will all receive Q2W dosing for the initial 26 weeks of the study. Participants transferring from study NN7769-4514, NN7769-4516, and NN7769-4728 will use the same treatment frequency as in their previous study (QW, Q2W, or QM) for the first 26 weeks of the study. Trial product strength will be either 2.0 mg/mL, 5.0 mg/mL, 11.3 mg/mL, 25.0 mg/mL, or 57.5 mg/

Treatment

The study intervention consists of the investigational medicinal product, Mim8, which will be administered to all study participants in three different treatment frequencies: QW, Q2W and QM. Participants transferring from study NN7769-4513 will all receive Q2W dosing for the initial 26 weeks of the study. Participants transferring from study NN7769-4514, NN7769-4516, and NN7769-4728 will use the same treatment frequency as in their previous study (QW, Q2W, or QM) for the first 26 weeks of the study. Trial product strength will be either 2.0 mg/mL, 5.0 mg/mL, 11.3 mg/mL, 25.0 mg/mL, or 57.5 mg/mL according to individual weight bands. Treatment will start on the maintenance dose, and no loading dose will be required.

Arm Label

Target Number of Participant

Arm Type

Arm Description

 Participants transferring from study NN7769-4513 will all receive Q2W dosing for the initial 26 weeks of the study. Trial product strength will be either 2.0 mg/mL, 5.0 mg/mL, 11.3 mg/mL, 25.0 mg/mL, or 57.5 mg/mL according to individual weight bands. Treatment will start on the maintenance dose, and no loading dose will be required.

Arm Label

Target Number of Participant

Arm Type

Arm Description

Participants transferring from study NN7769-4514, NN7769-4516, and NN7769-4728 will use the same treatment frequency as in their previous study (QW, Q2W, or QM) for the first 26 weeks of the study. Trial product strength will be either 2.0 mg/mL, 5.0 mg/mL, 11.3 mg/mL, 25.0 mg/mL, or 57.5 mg/mL according to individual weight bands. Treatment will start on the maintenance dose, and no loading dose will be required.

Gender

Age

Description

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 with diagnosis of congenital haemophilia A based on medical records
3. Ongoing participation in study 4513, 4514, 4516, or 4728 at the time of transfer. Participant
should qualify either of the following criteria:
a. Participant from study 4513, who has participated in the extension part of the study for at
least 12 weeks prior to enrolment in study 4532, or,
b. Participant has completed the end of treatment visit for study 4514,4516, or 4728.
4. Participant and/or participant’s parent(s)/participant’s LAR willingness and ability to comply
with scheduled visits and study procedures, including the completion of diary.

1. Any disorder, except for conditions associated with haemophilia, which in the investigator’s opinion might jeopardise participant’s safety or compliance with the protocol.
2. Participant who has discontinued or been withdrawn from studies 4513, 4514, 4516, or 4728.
3. Previous participation in this study. Participation is defined as signed informed consent.
4. Female who is pregnant, breast-feeding or intends to become pregnant.
5. Female of child-bearing potential and not using a highly effective contraceptive method (highly effective contraceptive measures as defined in Appendix 4 or as required by local regulation or practice).
6. Participation (i.e., signed informed consent) in any other interventional clinical study (except from study 4513, 4514, 4516, or 4728) of an approved or non-approved investigational medicinal product.
7. Any planned major surgery, during part 1 of the study. For definition of major surgery see (Table 6-7).
8. Mental incapacity, unwillingness

Number of treatment-emergent adverse events (TEAEs)

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Number of treated bleeding episodes

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Number of treated spontaneous bleeding episodes

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Number of treated traumatic bleeding episodes

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Number of treated joint bleeding episodes

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Number of treated target joint bleeding episodes (Arm 2)

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Mim8 plasma concentration

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Device handling experience using Haemophilia Device Assessment Tool (HDAT) (applicable for participants in Arm 2 only).

 From Visit 1 to visit 28