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

Haemophilia A Clinical Trial

— FRONTIER4  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05685238
• Other study ID #: NN7769-4532
• Secondary ID: U1111-1274-44262
• Status: Recruiting
• Phase: Phase 3
• Start date: February 13, 2023
• Est. completion date: June 30, 2028

Study information

• Verified date: April 2024
• Source: Novo Nordisk A/S
• Contact: Novo Nordisk
• Phone: (+1) 866-867-7178
• Email: clinicaltrials[@]novonordisk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 425
• Est. completion date: June 30, 2028
• Est. primary completion date: June 30, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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.

Related Conditions & MeSH terms

• Haemophilia A
• Haemophilia A With Inhibitors
• Hemophilia A

Intervention

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.

Locations

Country	Name	City	State
Austria	Universitätsklinik für Innere Medizin V	Innsbruck
Austria	Universitätsklinik für Innere Medizin V	Innsbruck
Austria	AKH - Klin. Abt. f. Haematologie u. Haemostaseologie	Wien
Austria	AKH - Klin. Abt. f. Haematologie u. Haemostaseologie	Wien
Belgium	Cliniques universitaires Saint-Luc - Service Hématologie	Bruxelles
Belgium	UZ Leuven - Kindergeneeskunde	Leuven
Bulgaria	UMHAT "Tsaritsa Yoanna-ISUL"	Sofia
Canada	McMaster University	Hamilton	Ontario
Canada	McMaster University	Hamilton	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario
China	Beijing Children's Hospital,Capital Medical University	Beijing	Beijing
China	Xiangya Hospital Central-South University	Changsha	Hunan
China	Chengdu Women's and Children's central hospital	Chengdu	Sichuan
China	Haemotology, Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The Children's Hospital, Zhejiang University school of medicine	Hangzhou	Zhejiang
China	Jinan Central Hospital	Jinan
China	Institute of hematology and Blood Diseases Hospital, Tianjin	Tianjin	Tianjin
China	Tongji Hospital, Tongji Medical College of HUST	Wuhan	Hubei
Denmark	Department of Haematology, 2081	København Ø
France	Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1	Bron
France	Ap-Hp-Hopital de Bicetre-1	Le Kremlin Bicetre Cedex
France	Centre Hospitalier Universitaire de Lille-Institut Coeur Poumon	Lille
France	Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu	Nantes
Germany	Vivantes Klinikum am Friedrichshain	Berlin
Germany	Rheinische Friedrich-Wilhelms-Universität Bonn	Bonn
Germany	HZRM Haemophilie-Zentrum Rhein Main GmbH	Mörfelden-Walldorf
India	SMS Medical College & Hospital	Jaipur	Rajasthan
India	Christian Medical College and Hospital	Ludhiana	Punjab
India	Seth GS medical college and KEM Hospital	Mumbai	Maharashtra
India	Post Graduate Institute of Child Health	Noida	Uttar Pradesh
India	Sahyadri Clinical Research And Development Center	Pune	Maharashtra
India	CMCV	Ranipet	Tamil Nadu
India	Nirmal Hospital Pvt. Ltd.	Surat	Gujarat
Ireland	St James's CRF	Dublin	Leinster
Ireland	St James's CRF	Dublin	Leinster
Israel	Sheba MC The Israeli National Hemophilia Center	Tel-Hashomer
Italy	AOU Careggi Firenze	Firenze
Italy	Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Ist Clinico Humanitas Centro Trombosi e Malattie Emorragiche	Milano
Italy	Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon	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
Japan	Nagoya University Hospital_Blood Transfusion	Aichi
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	Ogikubo Hospital_Pediatries & Blood	Tokyo
Japan	Ogikubo Hospital_Pediatries & Blood	Tokyo
Japan	Tokyo Medical Univ. Hospital_Laboratory Medicine	Tokyo
Korea, Republic of	Daejeon Eulji Medical Center, Eulji University	Daejeon
Korea, Republic of	Gangdong Kyung Hee University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Latvia	Children University Clinical Hospital	Riga
Latvia	Stradini Clinic of Oncology	Riga
Lithuania	Centre of Oncology and Hematology, Vilnius University	Vilnius
Lithuania	Vilnius University hospital Santaros klinikos	Vilnius
Malaysia	Hospital Ampang	Ampang, Selangor	Selangor
Malaysia	Hospital Queen Elizabeth 1	Kota Kinabalu	Sabah
Mexico	Centro Multidisciplinario Para El Desarrollo Especializado De La Investigación Clínica En Yucatán S.C.P. (CEMDEICY S.C.P.)	Merida
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	UMC Utrecht, Van Creveldkliniek	Utrecht
Poland	Szpital Uniwersytecki, Oddzial Kliniczny Hematologii	Krakow
Poland	Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa	Lublin
Poland	Uniwersytecki Szpital Kliniczny W Poznaniu	Poznan	Wielkopolskie
Poland	Intytut Hematologii i Transfuzjologii	Warszawa	Mazowieckie
Poland	Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego	Wroclaw	Dolnoslaskie
Portugal	Centro Hospitalar e Universitário de Coimbra	Coimbra
Portugal	Centro Hospitalar Lisboa Central - Hospital Dona Estefânia	Lisboa
Portugal	Centro Hospitalar de São João	Porto
Portugal	Centro Hospitalar Universitario De Santo Antonio E.P.E	Porto
Romania	Institut Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca	Cluj-Napoca
Saudi Arabia	King Faisal Specialist Hospital & Research Centre, Riyadh	Riyadh
Serbia	Clinical Centre of Serbia, Institute for Haematology	Belgrade
Serbia	Clinical Centre of Vojvodina, Haematology Clinic	Novi Sad
Slovakia	Univerzitna Nemocnica Martin	Martin
Slovakia	Vseobecna nemocnica Rimavska Sobota	Rimavska Sobota
Slovakia	Vranovska nemocnica, a.s.	Vranov nad Toplou
South Africa	Wits Bara Clinical Trial Site	Johannesburg	Gauteng
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Parktown, Johannesburg	Gauteng
Spain	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 Universitario Regional de Málaga	Málaga
Switzerland	Universitätsklinik für Hämatologie	Bern
Switzerland	Pädiatrische Onkologie-Hämatologie	Luzern 16
Switzerland	Zentrum für Labormedizin	St. Gallen
Switzerland	USZ Klinik für Medizinische Onkologie und Hämatologie	Zürich
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung City
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Acibadem Adana Hastanesi	Adana
Turkey	Gazi University	Ankara	Besevler/Ankara
Turkey	Gazi University	Ankara	Besevler/Ankara
Turkey	Hacettepe Universitesi	Ankara
Turkey	Akdeniz Universitesi	Antalya
Turkey	Ege Universitesi Tip Fakultesi	Bornova-IZMIR
Turkey	Istanbul University Oncology Institute	Capa-ISTANBUL
Turkey	Trakya University	Edirne
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Arthur Bloom Haemophilia Centre	Cardiff
United Kingdom	Evelina London Children's Hospital	London
United Kingdom	Royal Free Haemophilia Comprehensive Care Center	London
United Kingdom	St Thomas' Hospital	London
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	Children's Healthcare Atlanta	Atlanta	Georgia
United States	UC Denver Hemoph & Thrombo Ctr	Aurora	Colorado
United States	Rush University Med. Cntr	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Univ Hosp Cleveland Med Ctr	Cleveland	Ohio
United States	Dayton Children Hemostati Ctr	Dayton	Ohio
United States	Central Michigan University	Detroit	Michigan
United States	Penn State MS Hershey Med Ctr	Hershey	Pennsylvania
United States	Indiana Hemophilia-Thromb Ctr	Indianapolis	Indiana
United States	University of Iowa_Iowa City	Iowa City	Iowa
United States	Children's Hosp-Los Angeles	Los Angeles	California
United States	Univ of Miami/SCCC	Miami	Florida
United States	Vanderbilt U Med Ctr_Nashville	Nashville	Tennessee
United States	St Christopher Hosp for Child	Philadelphia	Pennsylvania
United States	St Joseph's Children's Hospita	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of injection site reactions	Measured as count of reactions.	From visit 1 (week 0) until end of treatment (up to 262 weeks)
Secondary	Occurrence of anti Mim8 antibodies	Measured as count of participants.	From visit 1 (week 0) until end of treatment (up to 262 weeks)
Secondary	Number of treated bleeding episodes	Measured as count of bleeds.	From visit 1 (week 0) until end of treatment (up to 262 weeks)
Secondary	Number of treated spontaneous bleeding episodes	Measured as count of bleeds.	From visit 1 (week 0) until end of treatment (up to 262 weeks)
Secondary	Number of treated traumatic bleeding episodes	Measured as count of bleeds.	From visit 1 (week 0) until end of treatment (up to 262 weeks)
Secondary	Number of treated joint bleeding episodes	Measured as count of bleeds.	From visit 1 (week 0) until end of treatment (up to 262 weeks)
Secondary	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)
Secondary	Mim8 plasma concentration	Measured as micrograms per milliliter (µg/mL).	From visit 1 (week 0) until end of treatment (up to 262 weeks)
Secondary	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)