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

Haemophilia A Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05053139
• Other study ID #: NN7769-4514
• Secondary ID: U1111-1249-43782
• Status: Recruiting
• Phase: Phase 3
• Start date: December 2, 2021
• Est. completion date: September 13, 2024

Study information

• Verified date: June 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 267
• Est. completion date: September 13, 2024
• Est. primary completion date: March 11, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years 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 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.

Related Conditions & MeSH terms

• Haemophilia A
• Haemophilia A With Inhibitors
• Hemophilia A

Intervention

Drug:
• NNC0365-3769 (Mim8)
Mim8 will be injected into a skinfold on the stomach with a thin needle either once a week or once a month.

Locations

Country	Name	City	State
Austria	Universitätsklinik für Innere Medizin V	Innsbruck
Austria	AKH - Klin. Abt. f. Haematologie u. Haemostaseologie	Wien
Belgium	Cliniques universitaires Saint-Luc - Service Hématologie	Bruxelles
Belgium	UZ Antwerpen - UZA - Kinderhemato-Oncologie	Edegem
Belgium	UZ Antwerpen - UZA - Kinderhemato-Oncologie	Edegem
Belgium	UZ Leuven - Kindergeneeskunde	Leuven
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	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	Haemotology, Nanfang Hospital, Southern Medical University	Guangzhou	Guangdong
China	The Children's Hospital, Zhejiang University school of medicine	Hangzhou	Zhejiang
China	Jinan Central Hospital	Ji'Nan	Shandong
China	The Second Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Institute of hematology and Blood Diseases Hospital, Tianjin	Tianjin	Tianjin
China	Tongji Hospital, Tongji Medical College of HUST	Wuhan	Hubei
Czechia	Ustav Hematologie a krevni tranfuze	Praha 2
Denmark	Department of Haematology, 2081	København Ø
France	Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1	Bron
France	Hôpital Cardiologique Louis Pradel	Bron Cedex
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	Hopital Necker	Paris
France	Hôpital Pontchaillou	Rennes
Germany	Vivantes Klinikum am Friedrichshain	Berlin
Germany	Rheinische Friedrich-Wilhelms-Universität Bonn	Bonn
Germany	HZRM Haemophilie-Zentrum Rhein Main GmbH	Frankfurt am Main
India	Christian medical college	Ludhiana	Punjab
India	Seth GS Medical College & KEM Hospital	Mumbai	Maharashtra
India	Post Graduate Institute of Child Health	Noida	Uttar Pradesh
India	CMCV	Ranipet	Tamil Nadu
India	Nirmal Hospital Pvt. Ltd.	Surat	Gujarat
Ireland	Crumlin Haematology	Dublin
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	Dipartimento di Ematologia Univ. Firenze	Firenze
Italy	Ist Clinico Humanitas Centro Trombosi e Malattie Emorragiche	Milano
Japan	Nagoya University Hospital_Blood Transfusion	Aichi
Japan	Hospital of the University of Occupational And Environmental Health Japan, Pediatrics	Kitakyusyu-shi, Fukuoka
Japan	Nanbu Medical Center & Children's Medical Center	Okinawa
Japan	Saitama Children's Med Centre_Hematology-Oncology	Saitama
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	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
Latvia	Children University Clinical Hospital	Riga
Latvia	Stradini Clinic of Oncology	Riga
Lithuania	Hospital of LUHS "Kauno Klinikos"	Kaunas
Lithuania	Children Oncohaematology department Children's Hospital,	Vilnius
Lithuania	Vilnius University hospital Santaros klinikos	Vilnius
Malaysia	Hospital Queen Elizabeth 1	Kota Kinabalu	Sabah
Malaysia	Hospital Ampang	Selangor Darul Ehsan
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	Malopolskie
Poland	Szpital Uniwersytecki, Oddzial Kliniczny Hematologii	Kraków	Malopolskie
Poland	Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa	Lublin
Poland	Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa	Lublin
Poland	Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego	Wroclaw	Dolnoslaskie
Poland	Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego	Wroclaw	Dolnoslaskie
Portugal	Centro Hospitalar e Universitário de Coimbra	Coimbra
Portugal	Centro Hospitalar de São João_Porto	Porto
Portugal	Centro Hospitalar de São João_Porto	Porto
Portugal	Unidade Local de Saúde de Santo António, E.P.E	Porto
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	Institutul Clinic Fundeni	Bucuresti
Romania	Institut Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca	Cluj-Napoca
Romania	Institut Oncologic "Prof. Dr. Ion Chiricuta" Cluj Napoca	Cluj-Napoca
Romania	Spitalul Clinic Municipal Filantropia Craiova	Craiova	Dolj
Romania	Spitalul Clinic Municipal Filantropia Craiova	Craiova	Dolj
Romania	Spitalul Clinic Municipal de Urgenta Timisoara	Timisoara
Russian Federation	Children Regional Clinical Hospital	Krasnodar
Russian Federation	Morozovskaya municipal children hospital	Moscow
Russian Federation	National Medical Research institution of haemotology	Moscow
Russian Federation	Republican Hospital n.a. V. A. Baranov	Petrozavodsk
Russian Federation	City out-patient clinic 37, City Hemophilia Centre	Saint-Petersburg
Saudi Arabia	King Faisal Specialist Hospital & Research Centre, Riyadh	Riyadh
Serbia	Clinical Centre of Serbia, Institute for Haematology	Belgrade
Serbia	Clinical Centre of Vojvodina	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	Wits Bara Clinical Trial Site	Johannesburg	Gauteng
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Parktown, Johannesburg	Gauteng
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Parktown, Johannesburg	Gauteng
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Regional de Málaga	Málaga
Switzerland	Universitätsklinik für Hämatologie	Bern
Switzerland	Zentrum für Labormedizin	St. Gallen
Switzerland	USZ Klinik für Medizinische Onkologie und Hämatologie	Zürich
Taiwan	Chung Shan Medical University Hospital	Taichung City
Taiwan	Chung Shan Medical University Hospital	Taichung City
Taiwan	Taichung Veterans General Hospital	Taichung City
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Acibadem Adana Hastanesi	Adana
Turkey	Gazi University	Ankara	Besevler/Ankara
Turkey	Gazi University	Ankara	Besevler/Ankara
Turkey	Akdeniz Universitesi	Antalya
Turkey	Ege Universitesi Tip Fakultesi	Bornova-IZMIR
Turkey	Istanbul University Oncology Institute	Capa-ISTANBUL
United Kingdom	Arthur Bloom Haemophilia Centre	Cardiff
United Kingdom	Royal Free Haemophilia Comprehensive Care Center	London
United Kingdom	St Thomas' Hospital	London
United Kingdom	Oxford Haemophilia Comprehensive Care Center	Oxford
United States	University Of Michigan	Ann Arbor	Michigan
United States	Children HC Atlanta-Adv Pediat	Atlanta	Georgia
United States	Univ of Colorado Sch of Med	Aurora	Colorado
United States	Univ Hosp Cleveland Med Ctr	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Dayton Children Hemostati Ctr	Dayton	Ohio
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	Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Children's Hosp-Los Angeles	Los Angeles	California
United States	Hemophilia Treatment Center	Los Angeles	California
United States	Univ of Miami/SCCC	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hosp-New Orleans	New Orleans	Louisiana
United States	Univ of NE Med Center_Omaha	Omaha	Nebraska
United States	St Christopher Hosp for Child	Philadelphia	Pennsylvania
United States	Arizona H&T Phoenix Child Hosp	Phoenix	Arizona
United States	Memorial Health Univ Med Ctr	Savannah	Georgia
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,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Malaysia,  Mexico,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Saudi Arabia,  Serbia,  Slovakia,  South Africa,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of treated bleeds	Count	No prophylaxis treatment (Arms 1, 2a and 2b): From randomisation (week 0) to end of main (week 26)
Primary	Number of treated bleeds	Count	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	Number of injection site reactions	Count	All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of main (week 26)
Secondary	Occurrence of anti-Mim8 antibodies	Count	All participants receiving Mim8 (Arms 2a, 2b, 3 and 4): From randomisation (week 0) to end of extension (week 52)
Secondary	Number of treated spontaneous bleeds	Count	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)
Secondary	Number of treated joint bleeds	Count	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)
Secondary	Number of treated traumatic bleeds	Count	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)
Secondary	Number of target joint bleeds	Count	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)
Secondary	Consumption of factor product per bleed treatment (number of injections)	Count	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)
Secondary	Change in physical function domain of PEDS-QL (pediatric quality of life inventory)	Score points Minimum score per question (best) = 0 Maximum score per question (worst) = 4 Total score for 13 questions: 0 (best) to 92 (worst)	All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)
Secondary	Change in patient's treatment burden using the Hemo-TEM (haemophilia treatment experience measure)	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'	All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)
Secondary	Change in patient's joint pain score using Joint Pain Rating Scale	Score points ranges from 0 = 'not at all' (best) to 4 = 'extremely' (worst)	All participants (Arms 1, 2a, 2b, 3 and 4): From randomisation (week 0) to the end of the main part (week 26)