A Research Study Looking at Long-term Treatment With Mim8 in People With Haemophilia A

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.

Первичные конечные точки

• Arm 1 and 2: Number of treatment emergent adverse events [Срок оценки: From week 0 until end of study (up to 283 weeks)]
• Arm 3: Number of treatment emergent adverse events [Срок оценки: From treatment initiation (week 0) until end of study (up to 124 weeks)]

Вторичные конечные точки (12)

• Arm 1 and 2: Number of injection site reactions [Срок оценки: From week 0 until end of treatment (up to 262 weeks)]
• Arm 1 and 2: Occurrence of anti Mim8 antibodies [Срок оценки: From week 0 until end of treatment (up to 262 weeks)]
• Arm 1 and 2: Number of treated bleeding episodes [Срок оценки: From week 0 until end of treatment (up to 262 weeks)]
• Arm 1 and 2: Number of treated spontaneous bleeding episodes [Срок оценки: From week 0 until end of treatment (up to 262 weeks)]
• Arm 1 and 2: Number of treated traumatic bleeding episodes [Срок оценки: From week 0 until end of treatment (up to 262 weeks)]
• Arm 1 and 2: Number of treated joint bleeding episodes [Срок оценки: From week 0 until end of treatment (up to 262 weeks)]
• Arm 2: Number of treated target joint bleeding episodes [Срок оценки: From week 0 until end of treatment (up to 262 weeks)]
• Arm 1 and 2: Mim8 plasma concentration [Срок оценки: From week 0 until end of treatment (up to 262 weeks)]
• Arm 2: Device handling using haemophilia device assessment tool (HDAT) (applicable for participants in arm 2 only) [Срок оценки: From week 26 until end of treatment (up to 262 weeks)]
• Arm 3: Number of injection site reactions [Срок оценки: From treatment initiation (week 0) until end of treatment (up to 103 weeks)]
• Arm 3: Occurrence of anti Mim8 antibodies [Срок оценки: From treatment initiation (week 0) until end of treatment (up to 103 weeks)]
• Arm 3: Number of treated bleeding episodes [Срок оценки: From treatment initiation (week 0) until end of treatment (up to 103 weeks)]

Критерии участия

Arm 1 \& 2:

Критерии включения

• 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.
• Male or female with diagnosis of congenital haemophilia A based on medical records.
• 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:

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

Критерии исключения

• 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.
• Participant who has discontinued or been withdrawn from studies NN7769-4513, NN7769-4514, NN7769-4516, or NN7769-4728.
• Previous participation in this study. Participation is defined as signed informed consent.
• Female who is pregnant, breast-feeding or intends to become pregnant.
• 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).
• 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.
• Any planned major surgery, during part 1 of the study.
• Mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation.

Arm 3:

Критерии включения

• 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.
• 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.
• Aged <1 year at the time of signing informed consent.
• Body weight greater than or equal to (≥) 3.2 kilograms at the time of signing informed consent.
• 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).
• Full-term pregnancy (gestational age ≥37 weeks).
• 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.
• 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.
• Receipt of vitamin K prophylaxis (as per local standard practice).
• Availability of historical results in medical records for:

• activated partial thromboplastin time (aPTT)
• FVIII levels.
• Availability of historical results in medical records or pre-dose sample taken for:

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

Критерии исключения

• Known or suspected hypersensitivity to trial product or related products.
• Previous participation in study 4532. Participation is defined as signed informed consent.
• 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.
• 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.
• Known congenital or acquired coagulation disorders other than haemophilia A.
• 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.
• Lack of adequate parental/legally acceptable representative (LAR) support to enter accurately and timely information regarding treatment and bleeding episodes into an (electronic) diary.
• 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.
• Any planned major surgery, during part 1 of Arm 3 (infant). For definition of major surgery.
• Immune tolerance induction planned to take place after treatment initiation.
• 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.
• Serum creatinine above 1.5 times the ULN.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 15 центров

• Children's Hospital Los Angeles - Endocrinology — Los Angeles
• UC Denver Hemoph & Thrombo Ctr — Aurora
• Univ of Miami/SCCC — Miami
• St Joseph's Hospital Foundation — Tampa
• Children's Healthcare Atlanta — Atlanta
• Rush University Med. Cntr — Chicago
• Rush University Medical Center — Chicago
• Indiana Hemophilia-Thromb Ctr — Indianapolis
• … и ещё 7 центров

Китай · 14 центров

• Beijing Children's Hospital, Capital Medical University — Пекин
• Beijing Children's Hospital，Capital Medical University — Пекин
• Haemotology, Nanfang Hospital, Southern Medical University — Гуанчжоу
• Nanfang Hospital, Southern Medical University-Haematology — Гуанчжоу
• Tongji Hospital, Tongji Medical College of HUST-Hematology — Ухань
• Tongji Hospital, Tongji Medical College of HUST — Ухань
• Xiangya Hospital Central-South University — Чанша
• Jinan Central Hospital Affiliated to Shandong University — Цзинань
• … и ещё 6 центров

Turkey (Türkiye) · 13 центров

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Индия · 11 центров

• Nirmal Hospital Pvt. Ltd. — Surat
• Nirmal Hospital Pvt. Ltd. — Surat
• Seth GS medical college and KEM Hospital — Mumbai
• Sahyadri Clinical Research And Development Center — Pune
• Sahyadri Clinical Research And Development Center — Pune
• Christian Medical College and Hospital — Ludhiana
• Christian Medical College and Hospital — Ludhiana
• SMS Medical College & Hospital — Jaipur
• … и ещё 3 центра

Италия · 10 центров

• A.O.U. Policlinico Umberto I — Rome
• AOU Careggi Firenze — Florence
• IRCCS Humanitas Research Hospital - Centro Trombosi e Malattie Emorragiche — Milan
• Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico — Milan
• Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon — Naples
• Azienda Ospedaliera Santobono Pausilipon - U.S.D. Centro Regionale Pediatrico Malattie del — Naples
• Ospedale Pediatrico Bambino Ges — Roma
• Ospedale Pediatrico Bambino Ges — Roma
• … и ещё 2 центра

Япония · 9 центров

• Nagoya University Hospital_Blood Transfusion — Aichi
• Ota Memorial Hospital_Pediatrics — Gunma
• Nara Medical University Hospital_Pediatrics — Nara
• Saitama Children's Med Centre_Hematology-Oncology — Saitama
• Jichi Medical University Hospital_Hematology — Tochigi
• Jichi Medical University Hospital_Pediatrics — Tochigi
• National Center for Child Health and Development_Hematology — Tokyo
• … и ещё 2 центра

Польша · 8 центров

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Франция · 7 центров

• Hospices Civils de Lyon- Hopital Louis Pradel — Bron
• Ap-Hp-Hopital de Bicetre-1 — Le Kremlin-Bicêtre
• Ap-Hp-Hopital de Bicetre — Le Kremlin-Bicêtre
• Centre Hospitalier Universitaire de Lille-Institut Coeur Poumon — Lille
• INSTITUT COEUR POUMON_Service d'hémostase et transfusion — Lille
• Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu — Nantes
• Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu — Nantes

Великобритания · 7 центров

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South Korea · 6 центров

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Испания · 5 центров

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Австрия · 4 центра

• Universitätsklinik für Innere Medizin V — Innsbruck
• Universitätsklinik für Innere Medizin V — Innsbruck
• AKH - Klin. Abt. f. Haematologie u. Haemostaseologie — Vienna
• AKH - Klin. Abt. f. Haematologie u. Haemostaseologie — Vienna

Португалия · 4 центра

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Швейцария · 4 центра

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Тайвань · 4 центра

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Германия · 3 центра

• Vivantes Netzwerk für Gesundheit GmbH - Vivantes Klinikum im Friedrichshain — Berlin
• Universitätsklinikum Bonn - Institut für Experimentelle Hämatologie — Bonn
• HZRM Haemophilie-Zentrum Rhein Main GmbH — Frankfurt am Main

Малайзия · 3 центра

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Словакия · 3 центра

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Бельгия · 2 центра

• Cliniques universitaires Saint-Luc - Service Hématologie — Brussels
• UZ Leuven - Kindergeneeskunde — Leuven

Канада · 2 центра

• McMaster University — Hamilton
• The Hospital for Sick Children — Toronto

Ирландия · 2 центра

• St James's CRF — Dublin
• St James's CRF — Dublin

Латвия · 2 центра

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Литва · 2 центра

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Нидерланды · 2 центра

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Сербия · 2 центра

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ЮАР · 2 центра

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Болгария · 1 центр

• SHAT of Haematological Diseases EAD, Clinic of Paediatric Clinical Haematology — Sofia

Дания · 1 центр

• Rigshospitalet - Department of Haematology, 2081 — København Ø

Израиль · 1 центр

• Sheba MC - The Israeli National Hemophilia Center — Tel Litwinsky

Мексика · 1 центр

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Румыния · 1 центр

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Саудовская Аравия · 1 центр

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Публикации

• Matsushita T, Banchev A, Bovet J, Chowdary P, Garcia Fernandez LM, Jimenez-Yuste V, Kavakli K, Kremer Hovinga JA, Windyga J, Young G. Denecimig (Mim8) prophylaxis once-every-2-weeks for hemophilia A with or without inhibitors - 26-week results from FRONTIER. Blood Adv. 2026 Jul 17:bloodadvances.2025019095. doi: 10.1182/bloodadvances.2025019095. Online ahead of print. PMID 42469164

Идентификаторы

NCT: NCT05685238 · NN7769-4532 · U1111-1274-4426 · 2022-502215-10

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗