A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A (FRONTIER 4) (FRONTIER4)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Haemophilia A With Inhibitors; Haemophilia A
• Intervention / Treatment: Drug: Mim8

• Study Type: Interventional
• Enrollment (Estimated): 425
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Austria
  • Innsbruck, Austria, A 6020
    • Recruiting
    • Universitätsklinik für Innere Medizin V
  • Innsbruck, Austria, A 6020
    • Not yet recruiting
    • Universitätsklinik für Innere Medizin V
  • Wien, Austria, 1090
    • Recruiting
    • AKH - Klin. Abt. f. Haematologie u. Haemostaseologie
  • Wien, Austria, 1090
    • Not yet recruiting
    • AKH - Klin. Abt. f. Haematologie u. Haemostaseologie
• Belgium
  • Bruxelles, Belgium, 1200
    • Recruiting
    • Cliniques universitaires Saint-Luc - Service Hématologie
  • Leuven, Belgium, 3000
    • Active, not recruiting
    • UZ Leuven - Kindergeneeskunde
• Bulgaria
  • Sofia, Bulgaria, 1527
    • Recruiting
    • UMHAT "Tsaritsa Yoanna-ISUL"
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Recruiting
      • McMaster University
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Not yet recruiting
      • McMaster University
    • Toronto, Ontario, Canada, M5G 1X8
      • Not yet recruiting
      • The Hospital for Sick Children
• China
  • Jinan, China, 250062
    • Not yet recruiting
    • Jinan Central Hospital
  • Beijing
    • Beijing, Beijing, China, 100045
      • Not yet recruiting
      • Beijing Children's Hospital，Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Not yet recruiting
      • Haemotology, Nanfang Hospital, Southern Medical University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Not yet recruiting
      • Tongji Hospital, Tongji Medical College of HUST
  • Hunan
    • Changsha, Hunan, China, 410008
      • Not yet recruiting
      • Xiangya Hospital Central-South University
  • Sichuan
    • Chengdu, Sichuan, China, 610074
      • Recruiting
      • Chengdu Women's and Children's Central Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of hematology and Blood Diseases Hospital, Tianjin
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310052
      • Not yet recruiting
      • The Children's Hospital, Zhejiang University school of medicine
• Denmark
  • København Ø, Denmark, 2100
    • Recruiting
    • Department of Haematology, 2081
• France
  • Bron, France, 69500
    • Not yet recruiting
    • Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1
  • Le Kremlin Bicetre Cedex, France, 94275
    • Not yet recruiting
    • Ap-Hp-Hopital de Bicetre-1
  • Lille, France, 59037
    • Not yet recruiting
    • Centre Hospitalier Universitaire de Lille-Institut Coeur Poumon
  • Nantes, France, Nantes
    • Not yet recruiting
    • Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu
• Germany
  • Berlin, Germany, 10249
    • Recruiting
    • Vivantes Klinikum am Friedrichshain
  • Bonn, Germany, 53127
    • Recruiting
    • Rheinische Friedrich-Wilhelms-Universität Bonn
  • Mörfelden-Walldorf, Germany, 64546
    • Active, not recruiting
    • HZRM Haemophilie-Zentrum Rhein Main GmbH
• India
  • Gujarat
    • Surat, Gujarat, India, 395002
      • Recruiting
      • Nirmal Hospital Pvt. Ltd.
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Recruiting
      • Seth GS medical college and KEM Hospital
    • Pune, Maharashtra, India, 411004
      • Not yet recruiting
      • Sahyadri Clinical Research And Development Center
  • Punjab
    • Ludhiana, Punjab, India, 141008
      • Recruiting
      • Christian Medical College and Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • Not yet recruiting
      • SMS Medical College & Hospital
  • Tamil Nadu
    • Ranipet, Tamil Nadu, India, 632 517
      • Recruiting
      • CMCV
  • Uttar Pradesh
    • Noida, Uttar Pradesh, India, 201303
      • Recruiting
      • Post Graduate Institute of Child Health
• Ireland
  • Leinster
    • Dublin, Leinster, Ireland, D08 A978
      • Recruiting
      • St James's CRF
    • Dublin, Leinster, Ireland, D08 A978
      • Not yet recruiting
      • St James's CRF
• Israel
  • Tel-Hashomer, Israel, 52621
    • Recruiting
    • Sheba MC The Israeli National Hemophilia Center
• Italy
  • Firenze, Italy, 50134
    • Recruiting
    • AOU Careggi Firenze
  • Milano, Italy, 20089
    • Recruiting
    • Ist Clinico Humanitas Centro Trombosi e Malattie Emorragiche
  • Milano, Italy, 20122
    • Not yet recruiting
    • Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
  • Napoli, Italy, 80122
    • Recruiting
    • Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon
  • Roma, Italy, 00165
    • Recruiting
    • Ospedale Pediatrico Bambino Ges
  • Rome, Italy, 00161
    • Active, not recruiting
    • A.O.U. Policlinico Umberto I
  • Torino, Italy, 10126
    • Withdrawn
    • A.O.U. Città della Salute e della Scienza di Torino-Ospedale
• Japan
  • Aichi, Japan, 466-8560
    • Recruiting
    • Nagoya University Hospital_Blood Transfusion
  • Nara, Japan, 634-8522
    • Not yet recruiting
    • Nara Medical University Hospital_Pediatrics
  • Saitama, Japan, 330-8777
    • Recruiting
    • Saitama Children's Med Centre_Hematology-Oncology
  • Tochigi, Japan, 329-0498
    • Recruiting
    • Jichi Medical University Hospital_Hematology
  • Tochigi, Japan, 329-0498
    • Recruiting
    • Jichi Medical University Hospital_Pediatrics
  • Tokyo, Japan, 157-8535
    • Recruiting
    • National Center for Child Health and Development_Hematology
  • Tokyo, Japan, 160-0023
    • Recruiting
    • Tokyo Medical Univ. Hospital_Laboratory Medicine
  • Tokyo, Japan, 167-0035
    • Recruiting
    • Ogikubo Hospital_Pediatries & Blood
  • Tokyo, Japan, 167-0035
    • Not yet recruiting
    • Ogikubo Hospital_Pediatries & Blood
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35233
    • Recruiting
    • Daejeon Eulji Medical Center, Eulji University
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 03722
    • Not yet recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05278
    • Recruiting
    • Gangdong Kyung Hee University Hospital
• Latvia
  • Riga, Latvia, LV-1002
    • Active, not recruiting
    • Stradini Clinic of Oncology
  • Riga, Latvia, LV-1004
    • Active, not recruiting
    • Children University Clinical Hospital
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Recruiting
    • Vilnius University Hospital Santaros Klinikos
  • Vilnius, Lithuania, LT-08406
    • Recruiting
    • Centre of Oncology and Hematology, Vilnius University
• Malaysia
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Recruiting
      • Hospital Queen Elizabeth 1
  • Selangor
    • Ampang, Selangor, Selangor, Malaysia, 68000
      • Recruiting
      • Hospital Ampang
• Mexico
  • Merida, Mexico, 97130
    • Not yet recruiting
    • Centro Multidisciplinario Para El Desarrollo Especializado De La Investigación Clínica En Yucatán S.C.P. (CEMDEICY S.C.P.)
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Recruiting
    • Academisch Medisch Centrum
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • UMC Utrecht, Van Creveldkliniek
• Poland
  • Krakow, Poland, 30-688
    • Recruiting
    • Szpital Uniwersytecki, Oddzial Kliniczny Hematologii
  • Lublin, Poland, 20-093
    • Recruiting
    • Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-556
      • Recruiting
      • Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-776
      • Recruiting
      • Intytut Hematologii i Transfuzjologii
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-569
      • Recruiting
      • Uniwersytecki Szpital Kliniczny w Poznaniu
• Portugal
  • Coimbra, Portugal, 3000-459
    • Not yet recruiting
    • Centro Hospitalar e Universitário de Coimbra
  • Lisboa, Portugal, 1169-045
    • Not yet recruiting
    • Centro Hospitalar Lisboa Central - Hospital Dona Estefânia
  • Porto, Portugal, 4200-319
    • Not yet recruiting
    • Centro Hospitalar de São João
  • Porto, Portugal, 4050-342
    • Not yet recruiting
    • Centro Hospitalar Universitario De Santo Antonio E.P.E
• Romania
  • Cluj-Napoca, Romania, 400015
    • Recruiting
    • Institut Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca
• Saudi Arabia
  • Riyadh, Saudi Arabia, 12713
    • Recruiting
    • King Faisal Specialist Hospital & Research Centre, Riyadh
• Serbia
  • Belgrade, Serbia, 11000
    • Not yet recruiting
    • Clinical Centre of Serbia, Institute for Haematology
  • Novi Sad, Serbia, 21000
    • Not yet recruiting
    • Clinical Centre of Vojvodina, Haematology Clinic
• Slovakia
  • Martin, Slovakia, 036 59
    • Active, not recruiting
    • Univerzitna nemocnica Martin
  • Rimavska Sobota, Slovakia, 979 01
    • Recruiting
    • Vseobecna nemocnica Rimavska Sobota
  • Vranov nad Toplou, Slovakia, 09327
    • Active, not recruiting
    • Vranovska nemocnica, a.s.
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2013
      • Not yet recruiting
      • Wits Bara Clinical Trial Site
    • Parktown, Johannesburg, Gauteng, South Africa, 2193
      • Recruiting
      • Charlotte Maxeke Johannesburg Academic Hospital
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Vall d'Hebron
  • Esplugues Llobregat, Spain, 08950
    • Recruiting
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Universitario Regional de Málaga
  • Málaga, Spain, 29010
    • Recruiting
    • Hospital Carlos Haya
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Universitätsklinik für Hämatologie
  • Luzern 16, Switzerland, 6000
    • Not yet recruiting
    • Pädiatrische Onkologie-Hämatologie
  • St. Gallen, Switzerland, 9008
    • Recruiting
    • Zentrum für Labormedizin
  • Zürich, Switzerland, 8091
    • Recruiting
    • USZ Klinik für Medizinische Onkologie und Hämatologie
• Taiwan
  • Taichung, Taiwan, 402
    • Recruiting
    • Chung Shan Medical University Hospital
  • Taichung City, Taiwan, 407
    • Recruiting
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, 100
    • Not yet recruiting
    • National Taiwan University Hospital
• Turkey
  • Adana, Turkey, 01130
    • Recruiting
    • Acibadem Adana Hastanesi
  • Ankara, Turkey, 06100
    • Active, not recruiting
    • Hacettepe Universitesi
  • Antalya, Turkey, 01010
    • Recruiting
    • Akdeniz Universitesi
  • Bornova-IZMIR, Turkey, 35100
    • Recruiting
    • Ege Universitesi Tip Fakultesi
  • Capa-ISTANBUL, Turkey, 34093
    • Recruiting
    • Istanbul University Oncology Institute
  • Edirne, Turkey, 22030
    • Active, not recruiting
    • Trakya University
  • Beşevler/Ankara
    • Ankara, Beşevler/Ankara, Turkey, 06500
      • Recruiting
      • Gazi University
    • Ankara, Beşevler/Ankara, Turkey, 06500
      • Not yet recruiting
      • Gazi University
• United Kingdom
  • Belfast, United Kingdom, BT9 78B
    • Not yet recruiting
    • Belfast City Hospital
  • Cardiff, United Kingdom, CF14 4XW
    • Recruiting
    • Arthur Bloom Haemophilia Centre
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • Evelina London Children's Hospital
  • London, United Kingdom, SE1 7EH
    • Recruiting
    • St Thomas' Hospital
  • London, United Kingdom, NW3 2QG
    • Recruiting
    • Royal Free Haemophilia Comprehensive Care Center
  • Sheffield, United Kingdom, S10 2JF
    • Not yet recruiting
    • Royal Hallamshire Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Recruiting
      • Children's Hosp-Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • UC Denver Hemoph & Thrombo Ctr
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Univ of Miami/SCCC
    • Tampa, Florida, United States, 33607
      • Recruiting
      • St Joseph's Children's Hospita
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Not yet recruiting
      • Children's Healthcare Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60612
      • Withdrawn
      • Rush University Med. Cntr
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Not yet recruiting
      • Indiana Hemophilia-Thromb Ctr
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa_Iowa City
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Not yet recruiting
      • Central Michigan University
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Univ Hosp Cleveland Med Ctr
    • Dayton, Ohio, United States, 45404
      • Recruiting
      • Dayton Children Hemostati Ctr
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-2360
      • Recruiting
      • Penn State MS Hershey Med Ctr
    • Philadelphia, Pennsylvania, United States, 19134
      • Recruiting
      • St Christopher Hosp for Child
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Not yet recruiting
      • Vanderbilt U Med Ctr_Nashville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (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 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.

Exclusion Criteria:

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 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; 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; 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.
Experimental: Arm 2; 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; 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.

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)

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): February 13, 2023
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: January 4, 2023
• First Posted (Actual): January 17, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: NN7769-4532; U1111-1274-4426 (Other Identifier: World Health Organization (WHO)); 2022-502215-10 (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