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

NCT ID: NCT05685238

Last Updated: 2025-12-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 451 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-13
• Study Completion Date: 2028-06-30

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). 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 June 2028, whichever comes first. Participants will get up to 262 injections; the number of injections depends on how often participants will get injections and how long time participants take part in the study. 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.

Conditions

Haemophilia A; Haemophilia A With Inhibitors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Participants entering from the multiple ascending dose (MAD) part of study NN7769-4513. In part 1, participants will receive Mim8 prophylaxis (PPX) subcutaneous (s.c.) administration using enhanced cartridge for 26 weeks. In part 2, participants will receive Mim8 PPX s.c. administration using enhanced cartridge or DV3407 pen-injector once it is approved.

Group Type: EXPERIMENTAL

Mim8

Intervention Type: DRUG

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 and 3 will use the DV3407 pen injector.

Arm 2

Participants entering from study NN7769-4514, NN7769-4728 and NN7769-4516. In part 1, participants will receive Mim8 PPX s.c. administration using DV3407 pen-injector for 26 weeks. In part 2, participants will receive Mim8 PPX s.c. administration using DV3407 pen-injector.

Group Type: EXPERIMENTAL

Mim8

Intervention Type: DRUG

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 and 3 will use the DV3407 pen injector.

Arm 3

In part 1 and 2, participants will receive Mim8 PPX s.c. administration using DV3407 pen-injector.

Group Type: EXPERIMENTAL

Mim8

Intervention Type: DRUG

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 and 3 will use the DV3407 pen injector.

Interventions

Mim8

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 and 3 will use the DV3407 pen injector.

Intervention Type: DRUG

Eligibility Criteria

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 based on medical records.

3. 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:

1. 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,

2. Participant has completed the end of treatment visit for study NN7769-4514, NN7769-4516 or NN7769-4728.

4. 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.

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 severe haemophilia A (endogenous FVIII activity less than (<) 1 percentage [%]) with or without FVIII inhibitors based on medical records.

3. Aged <1 year at the time of signing informed consent.

4. Body weight greater than or equal to (≥) 3.2 kilograms at the time of signing informed consent.

5. previously untreated patients (PUPs) or minimally treated patients (MTPs) (i.e., up to 5 days of exposure to haemophilia-related treatment such as plasma-derived FVIII, recombinant FVIII, fresh frozen plasma, cryoprecipitate, or whole blood products).

6. Full-term pregnancy (gestational age ≥37 weeks).

7. Participant's parent(s)/LAR(s) willingness and ability to comply with scheduled visits and Arm 3 (infant) procedures, including the completion of diary and patient reported outcome (PRO) questionnaire.

8. Participants <3 months of age must show no signs of active intracranial haemorrhage at screening. This is confirmed by cranial ultrasound performed according to local practice and regardless of delivery method.

9. Receipt of vitamin K prophylaxis (as per local standard practice).

10. Availability of historical results in medical records for:

a. activated partial thromboplastin time (aPTT) b. FVIII levels.

11. Availability of historical results in medical records or pre-dose sample taken for:

1. fibrinogen

2. haematology parameters

3. biochemistry parameters (aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT), bilirubin and creatinine).

Exclusion Criteria

1. 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.

2. Participant who has discontinued or been withdrawn from studies NN7769-4513, NN7769-4514, NN7769-4516, or NN7769-4728.

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 or as required by local regulation or practice).

6. 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.

7. Any planned major surgery, during part 1 of the study.

8. Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation.

Arm 3:

1. Known or suspected hypersensitivity to trial product or related products.

2. Previous participation in study 4532. Participation is defined as signed informed consent.

3. 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 enrolment.

4. 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 enrolment.

5. Known congenital or acquired coagulation disorders other than haemophilia A.

6. Other conditions (e.g., autoimmune disease) or laboratory abnormality that may increase the risk of bleeding or thrombosis, as evaluated by the investigator. 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.

8. Lack of adequate parental/legally acceptable representative (LAR) support to enter accurately and timely information regarding treatment and bleeding episodes into an (electronic) diary.

9. 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.

10. Any planned major surgery, during part 1 of Arm 3 (infant). For definition of major surgery.

11. Immune tolerance induction planned to take place after treatment initiation.

12. Hepatic dysfunction defined as AST and/or ALT greater than (>) 3 times the upper limit of normal (ULN) combined with total bilirubin >1.5 times the ULN.

13. Serum creatinine above 1.5 times the ULN.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Transparency dept. 2834

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

Children's Hospital Los Angeles - Endocrinology

Los Angeles, California, United States

UC Denver Hemoph & Thrombo Ctr

Aurora, Colorado, United States

Univ of Miami/SCCC

Miami, Florida, United States

St Joseph's Hospital Foundation

Tampa, Florida, United States

Children's Healthcare Atlanta

Atlanta, Georgia, United States

Rush University Med. Cntr

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Indiana Hemophilia-Thromb Ctr

Indianapolis, Indiana, United States

University of Iowa_Iowa City

Iowa City, Iowa, United States

Central Michigan University

Detroit, Michigan, United States

Univ Hosp Cleveland Med Ctr

Cleveland, Ohio, United States

Dayton Children Hemostati Ctr

Dayton, Ohio, United States

Penn State MS Hershey Med Ctr

Hershey, Pennsylvania, United States

St Christopher Hosp for Child

Philadelphia, Pennsylvania, United States

Vanderbilt U Med Ctr_Nashville

Nashville, Tennessee, United States

Universitätsklinik für Innere Medizin V

Innsbruck, , Austria

Universitätsklinik für Innere Medizin V

Innsbruck, , Austria

AKH - Klin. Abt. f. Haematologie u. Haemostaseologie

Vienna, , Austria

Cliniques universitaires Saint-Luc - Service Hématologie

Brussels, , Belgium

UZ Leuven - Kindergeneeskunde

Leuven, , Belgium

UMHAT Tsaritsa Yoanna - ISUL EAD, Pediatric clinical hematology and oncology

Sofia, , Bulgaria

McMaster University

Hamilton, Ontario, Canada

The Hospital for Sick Children

Toronto, Ontario, Canada

Beijing Children's Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Beijing Children's Hospital，Capital Medical University

Beijing, Beijing Municipality, China

Haemotology, Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

Nanfang Hospital, Southern Medical University-Haematology

Guangzhou, Guangdong, China

Tongji Hospital, Tongji Medical College of HUST-Hematology

Wuhan, Hubei, China

Tongji Hospital, Tongji Medical College of HUST

Wuhan, Hubei, China

Xiangya Hospital Central-South University

Changsha, Hunan, China

Jinan Central Hospital Affiliated to Shandong University

Jinan, Shandong, China

Jinan Central Hospital

Jinan, Shandong, China

Chengdu Women's and Children's Central Hospital

Chengdu, Sichuan, China

Institute of Hematology and Blood Diseases Hospital, Tianjin-Hematology

Tianjin, Tianjin Municipality, China

Children's Hospital, Zhejiang University School of Medicine-Hematology

Huzhou, Zhejiang, China

Jinan Central Hospital

Jinan, , China

Rigshospitalet - Department of Haematology, 2081

København Ø, , Denmark

Hospices Civils de Lyon- Hopital Louis Pradel

Bron, , France

Ap-Hp-Hopital de Bicetre-1

Le Kremlin-Bicêtre, , France

Centre Hospitalier Universitaire de Lille-Institut Coeur Poumon

Lille, , France

Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu

Nantes, , France

Vivantes Netzwerk für Gesundheit GmbH - Vivantes Klinikum im Friedrichshain

Berlin, , Germany

Universitätsklinikum Bonn - Institut für Experimentelle Hämatologie

Bonn, , Germany

HZRM Haemophilie-Zentrum Rhein Main GmbH

Frankfurt am Main, , Germany

Nirmal Hospital Pvt. Ltd.

Surat, Gujarat, India

Seth GS medical college and KEM Hospital

Mumbai, Maharashtra, India

Sahyadri Clinical Research And Development Center

Pune, Maharashtra, India

Christian Medical College and Hospital

Ludhiana, Punjab, India

SMS Medical College & Hospital

Jaipur, Rajasthan, India

CMCV

Ranipet, Tamil Nadu, India

Post Graduate Institute of Child Health

Noida, Uttar Pradesh, India

Seth GS medical college and KEM Hospital

Mumbai, , India

St James's CRF

Dublin, Leinster, Ireland

Sheba MC - The Israeli National Hemophilia Center

Tel Litwinsky, , Israel

A.O.U. Policlinico Umberto I

Rome, Lazio, Italy

AOU Careggi Firenze

Florence, , Italy

IRCCS Humanitas Research Hospital - Centro Trombosi e Malattie Emorragiche

Milan, , Italy

Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon

Napoli, , Italy

Azienda Ospedaliera Santobono Pausilipon - U.S.D. Centro Regionale Pediatrico Malattie della Coagulazione

Napoli, , Italy

Ospedale Pediatrico Bambino Ges

Roma, , Italy

A.O.U. Policlinico Umberto I

Rome, , Italy

A.O.U. Città della Salute e della Scienza di Torino-Ospedale

Torino, , Italy

Nagoya University Hospital_Blood Transfusion

Aichi, , Japan

Ota Memorial Hospital_Pediatrics

Gunma, , Japan

Nara Medical University Hospital_Pediatrics

Nara, , Japan

Saitama Children's Med Centre_Hematology-Oncology

Saitama, , Japan

Jichi Medical University Hospital_Hematology

Tochigi, , Japan

Jichi Medical University Hospital_Pediatrics

Tochigi, , Japan

National Center for Child Health and Development_Hematology

Tokyo, , Japan

Tokyo Medical Univ. Hospital_Laboratory Medicine

Tokyo, , Japan

Ogikubo Hospital_Pediatries & Blood

Tokyo, , Japan

Stradini Clinic of Oncology

Riga, , Latvia

Children University Clinical Hospital

Riga, , Latvia

Vilnius University hospital Santaros klinikos

Vilnius, , Lithuania

Centre of Oncology and Hematology, Vilnius University

Vilnius, , Lithuania

Hospital Queen Elizabeth 1

Kota Kinabalu, Sabah, Malaysia

Hospital Ampang

Ampang, Selangor, Selangor, Malaysia

Centro Multidisciplinario Para El Desarrollo Especializado De La Investigación Clínica En Yucatán S.C.P. (CEMDEICY S.C.P.)

Mérida, , Mexico

Academisch Medisch Centrum

Amsterdam, , Netherlands

UMC Utrecht, Van Creveldkliniek

Utrecht, , Netherlands

Uniwersytecki Szpital Kliniczny W Poznaniu

Poznan, Greater Poland Voivodeship, Poland

Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego

Wroclaw, Lower Silesian Voivodeship, Poland

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, Poland

Intytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, Poland

Szpital Uniwersytecki, Oddzial Kliniczny Hematologii

Krakow, , Poland

Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa

Lublin, , Poland

Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego

Wroclaw, , Poland

Unidade Local de Saúde de Coimbra, E.P.E.

Coimbra, , Portugal

Unidade Local de Saúde São José EPE- Hospital D. Estefânia

Lisbon, , Portugal

Centro Hospitalar Universitario De Santo Antonio E.P.E

Porto, , Portugal

Unidade Local de Saude de Sao Joao E.P.E

Porto, , Portugal

Institut Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca

Cluj-Napoca, , Romania

King Faisal Specialist Hospital & Research Centre, Riyadh

Riyadh, , Saudi Arabia

Clinical Centre of Serbia, Institute for Haematology

Belgrade, , Serbia

Clinical Centre of Vojvodina

Novi Sad, , Serbia

Univerzitna Nemocnica Martin

Martin, , Slovakia

Vseobecna nemocnica Rimavska Sobota

Rimavská Sobota, , Slovakia

Vranovska nemocnica, a.s.

Vranov nad Topľou, , Slovakia

Wits Bara Clinical Trial Site

Johannesburg, Gauteng, South Africa

Charlotte Maxeke Johannesburg Academic Hospital

Parktown, Johannesburg, Gauteng, South Africa

Daejeon Eulji Medical Center, Eulji University

Daejeon, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Gangdong Kyung Hee University Hospital

Seoul, , South Korea

Kyung Hee University Hospital at Gangdong

Seoul, , South Korea

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Sant Joan de Déu

Esplugues Llobregat, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Carlos Haya

Málaga, , Spain

Hospital Regional Universitario de Málaga

Málaga, , Spain

Universitätsklinik für Hämatologie

Bern, , Switzerland

Pädiatrische Onkologie-Hämatologie

Lucerne, , Switzerland

Zentrum für Labormedizin

Sankt Gallen, , Switzerland

Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie

Zurich, , Switzerland

Chung Shan Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital_main

Taipei, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Gazi University

Ankara, Beşevler/Ankara, Turkey (Türkiye)

Gazi Üniversitesi Hastanesi- Hematoloji

Ankara, Beşevler/Ankara, Turkey (Türkiye)

Istanbul University Oncology Institute

Capa-ISTANBUL, Capa-ISTANBUL, Turkey (Türkiye)

İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Onkoloji Enstitüsü

Capa-ISTANBUL, Capa-ISTANBUL, Turkey (Türkiye)

Akdeniz Üniversitesi Hastanesi- Hematoloji

Antalya, Konyaaltı/ Antalya, Turkey (Türkiye)

Acıbadem Adana Hastanesi-Hematoloji

Adana, , Turkey (Türkiye)

Hacettepe Universitesi

Ankara, , Turkey (Türkiye)

Hacettepe Üniversitesi Hastanesi- Hematoloji

Ankara, , Turkey (Türkiye)

Akdeniz Universitesi

Antalya, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi

Bornova-IZMIR, , Turkey (Türkiye)

Ege Üniversitesi Hastanesi- Hematoloji

Bornova-IZMIR, , Turkey (Türkiye)

Trakya University

Edirne, , Turkey (Türkiye)

Trakya Üniversitesi Tıp Fakültesi Hastanesi-Hematoloji

Edirne, , Turkey (Türkiye)

Belfast City Hospital

Belfast, , United Kingdom

University Hospital of Wales - Haemophilia

Cardiff, , United Kingdom

Royal Free Haemophilia Comprehensive Care Center

London, , United Kingdom

Royal Free Hospital - Haemophilia

London, , United Kingdom

Evelina London Children's Hospital - Haemophilia

London, , United Kingdom

St Thomas' Hospital - Haemostasis and Thrombosis Centre

London, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Countries

United States; Austria; Belgium; Bulgaria; Canada; China; Denmark; France; Germany; India; Ireland; Israel; Italy; Japan; Latvia; Lithuania; Malaysia; Mexico; Netherlands; Poland; Portugal; Romania; Saudi Arabia; Serbia; Slovakia; South Africa; South Korea; Spain; Switzerland; Taiwan; Turkey (Türkiye); United Kingdom

Other Identifiers

U1111-1274-4426

Identifier Type: OTHER

Identifier Source: secondary_id

2022-502215-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NN7769-4532

Identifier Type: -

Identifier Source: org_study_id