Clinical trial NCT05878938: A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People With Haemophilia A (FRONTIER 5)
Official title: Open-label Safety Study in Adults and Adolescents With Haemophilia A With and Without FVIII Inhibitors Switching Directly From Emicizumab Prophylaxis to NNC0365-3769 (Mim8) Prophylaxis
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: 2023-05-30
Enrollment: 61
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is looking at how safe it is to switch from emicizumab to Mim8, in people with haemophilia A. Mim8 is a new medicine that is used to prevent bleeding episodes in people with haemophilia A. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). Mim8 will be injected under the skin using a pen-injector either once every week, once every two weeks or once every month. The participants will be trained in using the pen injector. The participants can choose themselves, in collaboration with the study doctor how often they get Mim8 in this study. When the participant will get their first Mim8 injection depends on their current treatment with emicizumab. The participants will get their first Mim8 injection at Visit 2. Participants will have between 6 and 27 Mim8 injections. The total number of injections participants will have depends on their dosing frequency. The study will last for about 6-12 months. While taking part in this study, there are some restrictions about what medicine participant 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.


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 with diagnosis of congenital haemophilia A of any severity based on medical records.
3. Age 12 years or above at the time of signing the informed consent.
4. Participants treated with emicizumab once-weekly (QW), once every two weeks (Q2W), or once every four weeks (Q4W) according to the label for at least 8 weeks prior to screening.
5. Participants choosing to discontinue emicizumab treatment and switch to Mim8 QW, Q2W, or once-monthly (QM) treatment for 26 weeks from start of treatment (Visit 2).
6. Participant and/or caregiver willingness and ability to comply with scheduled visits and study procedures, including the completion of an electronic diary and patient-reported outcomes (PRO) questionnaires.

Exclusion Criteria:

1. Participation (i.e., signed informed consent) in any interventional, clinical study, with the exception of emicizumab, with receipt of the last dose within 8 weeks (or 5 half-lives of the investigational medicinal product \[IMP\], whichever is longer) before screening.
2. Any disorder, which in the investigator's opinion might jeopardise the participant's compliance with the protocol or safety, including ongoing Adverse Events (AEs) associated with emicizumab.
3. Previous participation in this study. Participation is defined as signed informed consent.
4. Known congenital or acquired coagulation disorders other than haemophilia A.
5. 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.
6. Neutralising antibodies towards emicizumab have been detected or, for patients adherent to emicizumab therapy, are suspected based on clinical and laboratory assessments.
7. Receipt of FVIII gene therapy at any time.
8. Ongoing or planned immune tolerance induction therapy.
9. Minor or major surgery planned to take place after screening and during the 26-week treatment period.
10. Known or suspected hypersensitivity to study intervention, related products, any constituents of the product or to other monoclonal antibodies.
11. Hepatic dysfunction defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) greater than (\>) 3 times the upper limit combined with total bilirubin \>1.5 times the upper limit measured at screening.
12. Renal impairment defined as estimated glomerular filtration rate (eGFR) lesser than or equal to (≤) 30 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) for serum creatinine measured at screening.
13. Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method.
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 treatment-emergent adverse events
timeFrame: From Visit 2 (week 0) until week 26
Secondary outcomes:
measure: Device handling experience using the Hemophilia Device Handling and Preference Assessment (HDHPA) questionnaire
timeFrame: Visit 8 (after 26 weeks of treatment)
measure: Change in participants' treatment burden using the Hemophilia treatment experience measure (Hemo-TEM) total score
timeFrame: From Visit 2 (week 0) until end of treatment (up to 26 weeks)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles - Endocrinology
state: California
city: Aurora
country: United States
facility: UC Denver Hemoph & Thrombo Ctr
state: Colorado
city: Tampa
country: United States
facility: St Joseph's Children's Hospita
state: Florida
city: Iowa City
country: United States
facility: University of Iowa_Iowa City
state: Iowa
city: Detroit
country: United States
facility: Central Michigan University
state: Michigan
city: Cleveland
country: United States
facility: Univ Hosp Cleveland Med Ctr
state: Ohio
city: Hershey
country: United States
facility: Penn State MS Hershey Med Ctr
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt U Med Ctr_Nashville
state: Tennessee
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: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Bron
country: France
facility: Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1
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: Firenze
country: Italy
facility: AOU Careggi Firenze
city: Milano
country: Italy
facility: Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon
city: Nara
country: Japan
facility: Nara Medical University Hospital_Pediatrics
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: Parktown, Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: Cardiff
country: United Kingdom
facility: Arthur Bloom Haemophilia Centre
city: London
country: United Kingdom
facility: Royal Free Haemophilia Comprehensive Care Center
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: