A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors

Phase 3

Completed

• Conditions: Haemophilia A; Haemophilia A With Inhibitors
• Interventions: Drug: NNC0365-3769 (Mim8)

• Registration Number: NCT05053139
• Lead Sponsor: Novo Nordisk A/S

Brief Summary

This study is investigating how Mim8 works compared to other medicines in people with haemophilia A, who either have inhibitors or do not have inhibitors. Mim8 is a new medicine that will be used for prevention of bleeding episodes. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII).

When and how often participants will receive Mim8 is dependent on their previous treatment - but is otherwise decided by chance. Mim8 will be injected into a skinfold on the stomach with a thin needle either once a week or once a month.

The study will last 54-124 weeks (12-29 months) depending on how long participants will be followed in run-in before they start treatment and if they continue in the follow period or transfer to an open label extension study. Participants will have 12-17 clinic visits.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-13
• Study First Submitted QC: 2021-09-13
• Study First Posted: 2021-09-22
• Study Start: 2021-12-02
• Primary Completion: 2024-03-11
• Study Completion: 2024-12-17
• Disposition First Posted: 2025-02-19
• Status Verified: 2025-03
• Disposition First Submitted: 2025-03-10
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 281

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 participants with diagnosis of congenital haemophilia A of any severity based on medical records.
3. Participant has been prescribed treatment with factor VIII concentrates or bypassing agent in the last 26 weeks prior to screening.
4. Age above or equal to 12 years at the time of signing informed consent.
5. Body weight greater than or equal to 30 kg.
6. Applicable to participants treated with on-demand/no prophylaxis prior to enrolment: ≥5 bleeds in the last 26 weeks prior to screening visit, for which factor VIII concentrates or bypassing agent has been prescribed.
7. Applicable to participants with FVIII activity ≥1% who are on prophylactic treatment: ≥1 bleed in the last 26 weeks prior to screening visit, for which factor VIII concentrates or bypassing agent has been prescribed.
8. Willingness and ability to comply with scheduled visits and study procedures, including the completion of diary and patient-reported outcomes questionnaires.

Exclusion Criteria

1. Previous participation in this study. Participation is defined as signed informed consent.
2. 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 randomisation.
3. 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 randomisation, for participants not included in the run-in.
4. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method. Breast feeding is allowed only during the run-in period.
5. 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.
6. Known or suspected hypersensitivity to trial product(s), any constituents of the product or to related products.
7. Receipt of gene therapy at any given time point.
8. Ongoing or planned immune tolerance induction (ITI) therapy.
9. Major surgery planned to take place after screening.
10. Known congenital or acquired coagulation disorders other than haemophilia A.
11. Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above 3 times the upper limit combined with total bilirubin above1.5 times the upper limit measured at screening.
12. Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below or equal to 30 ml/min/1.73 m^2 for serum creatinine measured at screening.
13. 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.
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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
no PPX- no PPX - Mim8 PPXQW/QM	NNC0365-3769 (Mim8)	Participants not receiving prophylaxis will not enter the run-in period. In arm 1, participants will be randomised to continue no prophylaxis (on-demand treatment with their Standard of Care products) or Mim8 once-weekly or once-monthly prophylaxis in agreement with investigators in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) in agreement with the investigator, either weekly or monthly Mim8 prophylaxis regimen.
PPX - Mim8 PPXQW	NNC0365-3769 (Mim8)	Participants on coagulation factor prophylaxis prior to enrolment will preferably continue the same product type and dosing frequency in the run-in period for at least 26 weeks before they can be randomised into the main part of the study. These participants will only be allowed to receive coagulation factor prophylaxis. In arm 3, participants will be randomised to once-weekly Mim8 prophylaxis regimen in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) on once-weekly Mim8 prophylaxis regimen.
no PPX - Mim8 PPXQW - Mim8 PPXQW	NNC0365-3769 (Mim8)	Participants not receiving prophylaxis will not enter the run-in period. In arm 2a, participants will be randomised to Mim8 once-weekly prophylaxis in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) on once-weekly Mim8 prophylaxis regimen.
PPX- Mim8 PPXQM	NNC0365-3769 (Mim8)	Participants on coagulation factor prophylaxis prior to enrolment will preferably continue the same product type and dosing frequency in the run-in period for at least 26 weeks before they can be randomised into the main part of the study. These participants will only be allowed to receive coagulation factor prophylaxis. In arm 4, participants will be randomised to once-monthly Mim8 prophylaxis regimen in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) on once-monthly Mim8 prophylaxis regimen.
no PPX - Mim8 PPXQM - Mim8 PPXQM	NNC0365-3769 (Mim8)	Participants not receiving prophylaxis will not enter the run-in period. In arm 2b, participants will be randomised to Mim8 once-monthly prophylaxis in the main part of the study (26 weeks). After the main part, participants will continue in the extension part of the study (26 weeks) on once-monthy Mim8 prophylaxis regimen.

Primary Outcome Measures

Name	Time	Method
Number of treated bleeds	Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from randomisation (week 0) to end of main (week 26)	Count

Secondary Outcome Measures

Name	Time	Method
Number of target joint bleeds	No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26)	Count
Number of treated traumatic bleeds	No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26)	Count
Number of injection site reactions	All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of main (week 26)	Count
Occurrence of anti-Mim8 antibodies	All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of extension (week 52)	Count
Number of treated spontaneous bleeds	No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26)	Count
Number of treated joint bleeds	No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26)	Count
Consumption of factor product per bleed treatment (number of injections)	No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (Week 26) Prophylaxis treatment (Arms 3 and 4): From initiation of run-in (26-52 weeks prior to week 0) to week 0 and from week 0 to end of main (week 26)	Count
Change in physical function domain of PEDS-QL (pediatric quality of life inventory)	All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)	Score points Minimum score per question (best) = 0 Maximum score per question (worst) = 4 Total score for 13 questions: 0 (best) to 92 (worst)
Change in patient's treatment burden using the Hemo-TEM (haemophilia treatment experience measure)	All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)	Score points; Ranges from 0 (best) - 4 (worst) representing answers ranging: 'Not at all difficult' - 'Extremely difficult' 'Never' - 'always' 'Not at all bothered' - 'Extremely bothered' 'Not at all interfering' - 'Extremely interfering' 'Not at all burdened' - 'Extremely burdened'
Change in patient's joint pain score using Joint Pain Rating Scale	All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)	Score points ranges from 0 = 'not at all' (best) to 4 = 'extremely' (worst)

Trial Locations

Locations (108)

Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego; 🇵🇱 Wroclaw, Dolnoslaskie, Poland

Szpital Uniwersytecki, Oddzial Kliniczny Hematologii; 🇵🇱 Kraków, Małopolskie, Poland

Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa; 🇵🇱 Lublin, Poland

Unidade Local de Saúde de Coimbra, E.P.E.; 🇵🇹 Coimbra, Portugal

St Thomas' Hospital; 🇬🇧 London, United Kingdom

Oxford Haemophilia Comprehensive Care Center; 🇬🇧 Oxford, United Kingdom

Unidade Local de Saúde de Santo António, E.P.E; 🇵🇹 Porto, Portugal

Centro Hospitalar de São João_Porto; 🇵🇹 Porto, Portugal

ULS São João, E.P.E.; 🇵🇹 Porto, Portugal

Spitalul Clinic Municipal Filantropia Craiova; 🇷🇴 Craiova, Dolj, Romania

Institutul Clinic Fundeni; 🇷🇴 Bucuresti, Romania

Institut Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca; 🇷🇴 Cluj-Napoca, Romania

Morozovskaya municipal children hospital; 🇷🇺 Moscow, Russian Federation

Republican Hospital n.a. V. A. Baranov; 🇷🇺 Petrozavodsk, Russian Federation

City out-patient clinic 37, City Hemophilia Centre; 🇷🇺 Saint-Petersburg, Russian Federation

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; 🇸🇰 Rimavska Sobota, Slovakia

Vranovska nemocnica, a.s.; 🇸🇰 Vranov nad Toplou, Slovakia

Wits Bara Clinical Trial Site; 🇿🇦 Johannesburg, Gauteng, South Africa

Charlotte Maxeke Johannesburg Academic Hospital; 🇿🇦 Parktown, Johannesburg, Gauteng, South Africa

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Regional de Málaga; 🇪🇸 Málaga, Spain

Universitätsklinik für Hämatologie; 🇨🇭 Bern, Switzerland

Zentrum für Labormedizin; 🇨🇭 St. Gallen, Switzerland

Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie; 🇨🇭 Zürich, Switzerland

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Akdeniz Universitesi; 🇹🇷 Antalya, Turkey

Istanbul University Oncology Institute; 🇹🇷 Capa-ISTANBUL, Turkey

Arthur Bloom Haemophilia Centre; 🇬🇧 Cardiff, United Kingdom

Children's Hospital Los Angeles - Endocrinology; 🇺🇸 Los Angeles, California, United States

Univ of Colorado Sch of Med; 🇺🇸 Aurora, Colorado, United States

Univ of Miami/SCCC; 🇺🇸 Miami, Florida, United States

Univ Hosp Cleveland Med Ctr; 🇺🇸 Cleveland, Ohio, United States

Chung Shan Medical University Hospital; 🇨🇳 Taichung City, Taiwan

St Joseph's Children's Hospita; 🇺🇸 Tampa, Florida, United States

Indiana Hemophilia-Thromb Ctr; 🇺🇸 Indianapolis, Indiana, United States

University of Iowa_Iowa City; 🇺🇸 Iowa City, Iowa, United States

St Christopher Hosp for Child; 🇺🇸 Philadelphia, Pennsylvania, United States

UZ Leuven - Kindergeneeskunde; 🇧🇪 Leuven, Belgium

McMaster University; 🇨🇦 Hamilton, Ontario, Canada

The Hospital for Sick Children; 🇨🇦 Toronto, Ontario, Canada

Taichung Veterans General Hospital; 🇨🇳 Taichung City, Taiwan

Gazi University; 🇹🇷 Ankara, Beşevler/Ankara, Turkey

Cliniques universitaires Saint-Luc - Service Hématologie; 🇧🇪 Bruxelles, Belgium

Acibadem Adana Hastanesi; 🇹🇷 Adana, Turkey

Ege Universitesi Tip Fakultesi; 🇹🇷 Bornova-IZMIR, Turkey

Beijing Children's Hospital，Capital Medical University; 🇨🇳 Beijing, Beijing, China

Haemotology, Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China

Tongji Hospital, Tongji Medical College of HUST-Hematology; 🇨🇳 Wuhan, Hubei, China

Tongji Hospital, Tongji Medical College of HUST; 🇨🇳 Wuhan, Hubei, China

Jinan Central Hospital; 🇨🇳 Ji'Nan, Shandong, China

Hôpital Cardiologique Louis Pradel; 🇫🇷 Bron Cedex, 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, France

Royal Free Haemophilia Comprehensive Care Center; 🇬🇧 London, United Kingdom

Hopital Necker; 🇫🇷 Paris, France

Hôpital Pontchaillou; 🇫🇷 Rennes, France

Vivantes Klinikum am Friedrichshain - Innere Medizin - Angiologie und Hämostaseologie; 🇩🇪 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 & KEM Hospital; 🇮🇳 Mumbai, Maharashtra, India

Christian medical college; 🇮🇳 Ludhiana, Punjab, India

CMCV; 🇮🇳 Ranipet, Tamil Nadu, India

Post Graduate Institute of Child Health; 🇮🇳 Noida, Uttar Pradesh, India

St James's CRF; 🇮🇪 Dublin, Leinster, Ireland

Sheba MC The Israeli National Hemophilia Center; 🇮🇱 Tel-Hashomer, Israel

Dipartimento di Ematologia Univ. Firenze; 🇮🇹 Firenze, Italy

Ist Clinico Humanitas Centro Trombosi e Malattie Emorragiche; 🇮🇹 Milano, Italy

Nagoya University Hospital_Blood Transfusion; 🇯🇵 Aichi, Japan

Hospital of the University of Occupational And Environmental Health Japan, Pediatrics; 🇯🇵 Kitakyusyu-shi, Fukuoka, 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

Daejeon Eulji Medical Center, Eulji University; 🇰🇷 Daejeon, Korea, Republic of

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Gangdong Kyung Hee University Hospital; 🇰🇷 Seoul, Korea, Republic of

Stradini Clinic of Oncology; 🇱🇻 Riga, Latvia

Children University Clinical Hospital; 🇱🇻 Riga, Latvia

Children Oncohaematology department Children's Hospital,; 🇱🇹 Vilnius, Lithuania

Vilnius University hospital Santaros klinikos; 🇱🇹 Vilnius, Lithuania

Hospital Queen Elizabeth 1; 🇲🇾 Kota Kinabalu, Sabah, Malaysia

Hospital Ampang; 🇲🇾 Selangor Darul Ehsan, Malaysia

Centro Multidisciplinario Para El Desarrollo Especializado De La Investigación Clínica En Yucatán S.C.P. (CEMDEICY S.C.P.); 🇲🇽 Merida, Mexico

Academisch Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

UMC Utrecht, Van Creveldkliniek; 🇳🇱 Utrecht, Netherlands

Department of Haematology, 2081; 🇩🇰 København Ø, Denmark

Children HC Atlanta-Adv Pediat; 🇺🇸 Atlanta, Georgia, United States

Dayton Children Hemostati Ctr; 🇺🇸 Dayton, Ohio, United States

Penn State MS Hershey Med Ctr; 🇺🇸 Hershey, Pennsylvania, United States

Universitätsklinik für Innere Medizin V; 🇦🇹 Innsbruck, Austria

AKH - Klin. Abt. f. Haematologie u. Haemostaseologie; 🇦🇹 Wien, Austria

UZ Antwerpen - UZA - Kinderhemato-Oncologie; 🇧🇪 Edegem, Belgium

Xiangya Hospital Central-South University; 🇨🇳 Changsha, Hunan, China

Chengdu Women's and Children's central hospital; 🇨🇳 Chengdu, Sichuan, China

Institute of hematology and Blood Diseases Hospital, Tianjin-Hematology; 🇨🇳 Tianjin, Tianjin, China

Children's Hospital, Zhejiang University school of medicine; 🇨🇳 Hangzhou, Zhejiang, China

The Children's Hospital, Zhejiang University school of medicine; 🇨🇳 Hangzhou, Zhejiang, China

Ustav Hematologie a krevni tranfuze; 🇨🇿 Praha 2, Czechia