A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People With Haemophilia A (FRONTIER 5) (FRONTIER 5)

Open-label Safety Study in Adults and Adolescents With Haemophilia A With and Without FVIII Inhibitors Switching Directly From Emicizumab Prophylaxis to NNC0365-3769 (Mim8) Prophylaxis

This study is looking at how safe it is to switch from emicizumab to Mim8, in people with haemophilia A. Mim8 is a new medicine that is used to prevent bleeding episodes in people with haemophilia A. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). Mim8 will be injected under the skin using a pen-injector either once every week, once every two weeks or once every month. The participants will be trained in using the pen injector. The participants can choose themselves, in collaboration with the study doctor how often they get Mim8 in this study. When the participant will get their first Mim8 injection depends on their current treatment with emicizumab. The participants will get their first Mim8 injection at Visit 2. Participants will have between 6 and 27 Mim8 injections. The total number of injections participants will have depends on their dosing frequency. The study will last for about 6-12 months. While taking part in this study, there are some restrictions about what medicine participant 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.

Study Overview

• Status: Completed
• Conditions: Haemophilia A With Inhibitors; Haemophilia A
• Intervention / Treatment: Drug: NNC0365-3769 (Mim8) PPX

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Universitätsklinik für Innere Medizin V
  • Vienna, Austria, 1090
    • AKH - Klin. Abt. f. Haematologie u. Haemostaseologie
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc - Service Hématologie
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University
• France
  • Bron, France, 69500
    • Hospices Civils de Lyon- Hopital Louis Pradel-1
• Germany
  • Berlin, Germany, 10249
    • Vivantes Netzwerk für Gesundheit GmbH - Vivantes Klinikum im Friedrichshain
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn - Institut für Experimentelle Hämatologie
• Italy
  • Milan, Italy, 20122
    • Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
  • Napoli, Italy, 80122
    • Azienda Ospedaliera Di Rilievo Nazionale Santobono Pausilipon
  • Napoli, Italy, 80122
    • Azienda Ospedaliera Santobono Pausilipon - U.S.D. Centro Regionale Pediatrico Malattie della Coagulazione
  • Tuscany
    • Florence, Tuscany, Italy, 50134
      • AOU Careggi Firenze
• Japan
  • Nara, Japan, 634-8522
    • Nara Medical University Hospital_Pediatrics
• South Africa
  • Gauteng
    • Parktown, Johannesburg, Gauteng, South Africa, 2193
      • Charlotte Maxeke Johannesburg Academic Hospital
• South Korea
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, South Korea, 05278
    • Kyung Hee University Hospital at Gangdong
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
• United Kingdom
  • Belfast, United Kingdom, BT9 78B
    • Belfast City Hospital
  • Birmingham, United Kingdom
    • Birmingham Children's Hospital
  • Cardiff, United Kingdom, CF14 4XW
    • Arthur Bloom Haemophilia Centre
  • London, United Kingdom, NW3 2QG
    • Royal Free Haemophilia Comprehensive Care Center
  • London, United Kingdom, NW3 2QG
    • Royal Free Haemophilia Comprehensive Care Centre
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles - Endocrinology
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UC Denver Hemoph & Thrombo Ctr
  • Florida
    • Tampa, Florida, United States, 33607
      • St Joseph's Hospital Foundation
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta Univ/Childrens Hosp-GA
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Med. Cntr
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa_Iowa City
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Central Michigan University
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Univ Hosp Cleveland Med Ctr
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-2360
      • Penn State MS Hershey Med Ctr
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt U Med Ctr_Nashville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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 of any severity based on medical records.
3. Age 12 years or above at the time of signing the informed consent.
4. Participants treated with emicizumab once-weekly (QW), once every two weeks (Q2W), or once every four weeks (Q4W) according to the label for at least 8 weeks prior to screening.
5. Participants choosing to discontinue emicizumab treatment and switch to Mim8 QW, Q2W, or once-monthly (QM) treatment for 26 weeks from start of treatment (Visit 2).
6. Participant and/or caregiver willingness and ability to comply with scheduled visits and study procedures, including the completion of an electronic diary and patient-reported outcomes (PRO) questionnaires.

Exclusion Criteria:

1. Participation (i.e., signed informed consent) in any interventional, clinical study, with the exception of emicizumab, with receipt of the last dose within 8 weeks (or 5 half-lives of the investigational medicinal product [IMP], whichever is longer) before screening.
2. Any disorder, which in the investigator's opinion might jeopardise the participant's compliance with the protocol or safety, including ongoing Adverse Events (AEs) associated with emicizumab.
3. Previous participation in this study. Participation is defined as signed informed consent.
4. Known congenital or acquired coagulation disorders other than haemophilia A.
5. 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.
6. Neutralising antibodies towards emicizumab have been detected or, for patients adherent to emicizumab therapy, are suspected based on clinical and laboratory assessments.
7. Receipt of FVIII gene therapy at any time.
8. Ongoing or planned immune tolerance induction therapy.
9. Minor or major surgery planned to take place after screening and during the 26-week treatment period.
10. Known or suspected hypersensitivity to study intervention, related products, any constituents of the product or to other monoclonal antibodies.
11. Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than (>) 3 times the upper limit combined with total bilirubin >1.5 times the upper limit measured at screening.
12. Renal impairment defined as estimated glomerular filtration rate (eGFR) lesser than or equal to (≤) 30 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) for serum creatinine measured at screening.
13. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method.
14. Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation.
15. Other conditions (e.g. autoimmune disease) or laboratory abnormality that may increase risk of bleeding or thrombosis as evaluated by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NNC0365-3769 (Mim8) PPX; Participants will receive Mim8 prophylaxis (PPX) subcutaneous (s.c.) injection using a prefilled fixed dose DV3407-C1 pen-injector.	Drug: NNC0365-3769 (Mim8) PPX; Participants will receive Mim8 PPX once-weekly dosing (QW), once every two weeks dosing (Q2W), or once-monthly dosing s.c. injection using a prefilled fixed dose DV3407-C1 pen-injector for 26 weeks.

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 2 (week 0) until week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device handling experience using the Hemophilia Device Handling and Preference Assessment (HDHPA) questionnaire	Measured as percentage of participants. HDHPA measures device handling experience and device preference. The measure consists of 26 items that are reported individually. it is measures in units: Percentage of participants = the distribution of participant answers within each response category, for each of the 26 individual items.	Visit 8 (after 26 weeks of treatment)
Change in participants' treatment burden using the Hemophilia treatment experience measure (Hemo-TEM) total score	Measured as score points. Hemo-TEM measures treatment burden. The measure consists of 26 items yielding 5 domain scores and 1 total score. Domain scores (score range): Injection difficulties (0-100), physical impact (0-100), treatment bother (0-100), interference with daily life (0-100), and emotional impact (0-100). Total score ranges 0-100. Higher scores indicate greater treatment burden.	From Visit 2 (week 0) until end of treatment (up to 26 weeks)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2023
• Primary Completion (Actual): July 18, 2024
• Study Completion (Actual): July 19, 2024

Study Registration Dates

• First Submitted: May 12, 2023
• First Submitted That Met QC Criteria: May 12, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; protein phosphatase 4
• Other Study ID Numbers: NN7769-4728; U1111-1281-9323 (Other Identifier: World Health Organization (WHO)); 2022-003053-66 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No