Clinical trial NCT05053139: A Research Study Investigating Mim8 in Adults and Adolescents With Haemophilia A With or Without Inhibitors
Official title: A Multinational, Open-label, Randomised, Controlled Study to Investigate Efficacy and Safety of NNC0365-3769 (Mim8) in Adults and Adolescents With Haemophilia A With or Without Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Haemophilia A
Haemophilia A With Inhibitors
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-09-22
Enrollment: 281
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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.

Primary outcomes:
measure: Number of treated bleeds
timeFrame: No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (week 26)
measure: Number of treated bleeds
timeFrame: 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)
Secondary outcomes:
measure: Number of injection site reactions
timeFrame: All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of main (week 26)
measure: Occurrence of anti-Mim8 antibodies
timeFrame: All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of extension (week 52)
measure: Number of treated spontaneous bleeds
timeFrame: 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)
measure: Number of treated joint bleeds
timeFrame: 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)
measure: Number of treated traumatic bleeds
timeFrame: 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)
measure: Number of target joint bleeds
timeFrame: 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)
measure: Consumption of factor product per bleed treatment (number of injections)
timeFrame: 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)
measure: Change in physical function domain of PEDS-QL (pediatric quality of life inventory)
timeFrame: All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)
measure: Change in patient's treatment burden using the Hemo-TEM (haemophilia treatment experience measure)
timeFrame: All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)
measure: Change in patient's joint pain score using Joint Pain Rating Scale
timeFrame: All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles - Endocrinology
state: California
city: Aurora
country: United States
facility: Univ of Colorado Sch of Med
state: Colorado
city: Miami
country: United States
facility: Univ of Miami/SCCC
state: Florida
city: Tampa
country: United States
facility: St Joseph's Children's Hospita
state: Florida
city: Atlanta
country: United States
facility: Children HC Atlanta-Adv Pediat
state: Georgia
city: Indianapolis
country: United States
facility: Indiana Hemophilia-Thromb Ctr
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa_Iowa City
state: Iowa
city: Cleveland
country: United States
facility: Univ Hosp Cleveland Med Ctr
state: Ohio
city: Dayton
country: United States
facility: Dayton Children Hemostati Ctr
state: Ohio
city: Hershey
country: United States
facility: Penn State MS Hershey Med Ctr
state: Pennsylvania
city: Philadelphia
country: United States
facility: St Christopher Hosp for Child
state: Pennsylvania
city: Innsbruck
country: Austria
facility: Universitätsklinik für Innere Medizin V
city: Wien
country: Austria
facility: AKH - Klin. Abt. f. Haematologie u. Haemostaseologie
city: Bruxelles
country: Belgium
facility: Cliniques universitaires Saint-Luc - Service Hématologie
city: Edegem
country: Belgium
facility: UZ Antwerpen - UZA - Kinderhemato-Oncologie
city: Leuven
country: Belgium
facility: UZ Leuven - Kindergeneeskunde
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Beijing
country: China
facility: Beijing Children's Hospital，Capital Medical University
state: Beijing
city: Guangzhou
country: China
facility: Haemotology, Nanfang Hospital, Southern Medical University
state: Guangdong
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of HUST-Hematology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of HUST
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central-South University
state: Hunan
city: Ji'Nan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Chengdu
country: China
facility: Chengdu Women's and Children's central hospital
state: Sichuan
city: Tianjin
country: China
facility: Institute of hematology and Blood Diseases Hospital, Tianjin-Hematology
state: Tianjin
city: Hangzhou
country: China
facility: Children's Hospital, Zhejiang University school of medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Children's Hospital, Zhejiang University school of medicine
state: Zhejiang
city: Praha 2
country: Czechia
facility: Ustav Hematologie a krevni tranfuze
city: København Ø
country: Denmark
facility: Department of Haematology, 2081
city: Bron Cedex
country: France
facility: Hôpital Cardiologique Louis Pradel
city: Bron
country: France
facility: Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1
city: Le Kremlin Bicetre Cedex
country: France
facility: Ap-Hp-Hopital de Bicetre-1
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille-Institut Coeur Poumon
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu
city: Paris
country: France
facility: Hopital Necker
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Berlin
country: Germany
facility: Vivantes Klinikum am Friedrichshain - Innere Medizin - Angiologie und Hämostaseologie
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn - Institut für Experimentelle Hämatologie
city: Frankfurt am Main
country: Germany
facility: HZRM Haemophilie-Zentrum Rhein Main GmbH
city: Surat
country: India
facility: Nirmal Hospital Pvt. Ltd.
state: Gujarat
city: Mumbai
country: India
facility: Seth GS Medical College & KEM Hospital
state: Maharashtra
city: Ludhiana
country: India
facility: Christian medical college
state: Punjab
city: Ranipet
country: India
facility: CMCV
state: Tamil Nadu
city: Noida
country: India
facility: Post Graduate Institute of Child Health
state: Uttar Pradesh
city: Dublin
country: Ireland
facility: St James's CRF
state: Leinster
city: Tel-Hashomer
country: Israel
facility: Sheba MC The Israeli National Hemophilia Center
city: Firenze
country: Italy
facility: Dipartimento di Ematologia Univ. Firenze
city: Milano
country: Italy
facility: Ist Clinico Humanitas Centro Trombosi e Malattie Emorragiche
city: Aichi
country: Japan
facility: Nagoya University Hospital_Blood Transfusion
city: Kitakyusyu-shi, Fukuoka
country: Japan
facility: Hospital of the University of Occupational And Environmental Health Japan, Pediatrics
city: Saitama
country: Japan
facility: Saitama Children's Med Centre_Hematology-Oncology
city: Tochigi
country: Japan
facility: Jichi Medical University Hospital_Hematology
city: Tochigi
country: Japan
facility: Jichi Medical University Hospital_Pediatrics
city: Tokyo
country: Japan
facility: National Center for Child Health and Development_Hematology
city: Tokyo
country: Japan
facility: Tokyo Medical Univ. Hospital_Laboratory Medicine
city: Tokyo
country: Japan
facility: Ogikubo Hospital_Pediatries & Blood
city: Daejeon
country: Korea, Republic of
facility: Daejeon Eulji Medical Center, Eulji University
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Gangdong Kyung Hee University Hospital
city: Riga
country: Latvia
facility: Stradini Clinic of Oncology
city: Riga
country: Latvia
facility: Children University Clinical Hospital
city: Vilnius
country: Lithuania
facility: Children Oncohaematology department Children's Hospital,
city: Vilnius
country: Lithuania
facility: Vilnius University hospital Santaros klinikos
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth 1
state: Sabah
city: Selangor Darul Ehsan
country: Malaysia
facility: Hospital Ampang
city: Merida
country: Mexico
facility: Centro Multidisciplinario Para El Desarrollo Especializado De La Investigación Clínica En Yucatán S.C.P. (CEMDEICY S.C.P.)
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Utrecht
country: Netherlands
facility: UMC Utrecht, Van Creveldkliniek
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Szpital Uniwersytecki, Oddzial Kliniczny Hematologii
state: Małopolskie
city: Kraków
country: Poland
facility: Szpital Uniwersytecki, Oddzial Kliniczny Hematologii
state: Małopolskie
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa
city: Coimbra
country: Portugal
facility: Unidade Local de Saúde de Coimbra, E.P.E.
city: Porto
country: Portugal
facility: Unidade Local de Saúde de Santo António, E.P.E
city: Porto
country: Portugal
facility: Centro Hospitalar de São João_Porto
city: Porto
country: Portugal
facility: ULS São João, E.P.E.
city: Craiova
country: Romania
facility: Spitalul Clinic Municipal Filantropia Craiova
state: Dolj
city: Bucuresti
country: Romania
facility: Institutul Clinic Fundeni
city: Cluj-Napoca
country: Romania
facility: Institut Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca
city: Moscow
country: Russian Federation
facility: Morozovskaya municipal children hospital
city: Petrozavodsk
country: Russian Federation
facility: Republican Hospital n.a. V. A. Baranov
city: Saint-Petersburg
country: Russian Federation
facility: City out-patient clinic 37, City Hemophilia Centre
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Centre, Riyadh
city: Belgrade
country: Serbia
facility: Clinical Centre of Serbia, Institute for Haematology
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Martin
country: Slovakia
facility: Univerzitna Nemocnica Martin
city: Rimavska Sobota
country: Slovakia
facility: Vseobecna nemocnica Rimavska Sobota
city: Vranov nad Toplou
country: Slovakia
facility: Vranovska nemocnica, a.s.
city: Johannesburg
country: South Africa
facility: Wits Bara Clinical Trial Site
state: Gauteng
city: Parktown, Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Bern
country: Switzerland
facility: Universitätsklinik für Hämatologie
city: St. Gallen
country: Switzerland
facility: Zentrum für Labormedizin
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie
city: Taichung City
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung City
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Ankara
country: Turkey
facility: Gazi University
state: Beşevler/Ankara
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi
city: Antalya
country: Turkey
facility: Akdeniz Universitesi
city: Bornova-IZMIR
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Capa-ISTANBUL
country: Turkey
facility: Istanbul University Oncology Institute
city: Cardiff
country: United Kingdom
facility: Arthur Bloom Haemophilia Centre
city: London
country: United Kingdom
facility: Royal Free Haemophilia Comprehensive Care Center
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: Oxford
country: United Kingdom
facility: Oxford Haemophilia Comprehensive Care Center
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: