A Research Study Looking at How Safe it is to Switch From Emicizumab to Mim8 in People With Haemophilia A (FRONTIER 5)

Haemophilia A Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05878938
• Other study ID #: NN7769-4728
• Secondary ID: U1111-1281-93232
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 26, 2023
• Est. completion date: December 11, 2024

Study information

• Verified date: April 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: December 11, 2024
• Est. primary completion date: September 9, 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 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.

Related Conditions & MeSH terms

• Haemophilia A
• Haemophilia A With Inhibitors
• Hemophilia A

Intervention

Drug:
• NNC0365-3769 (Mim8) PPX
Participants will receive Mim8 PPX once-weekly dosing (QW), once every two weeks dosing (Q2W), or once-monthly dosing s.c. injection using a prefilled fixed dose DV3407-C1 pen-injector for 26 weeks.

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
Canada	McMaster University	Hamilton	Ontario
France	Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1	Bron
Germany	Vivantes Klinikum am Friedrichshain	Berlin
Germany	Rheinische Friedrich-Wilhelms-Universität Bonn	Bonn
Italy	AOU Careggi Firenze	Firenze
Italy	Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera di Rilievo Nazionale Santobono Pausilipon	Napoli
Japan	Nara Medical University Hospital_Pediatrics	Nara
Korea, Republic of	Gangdong Kyung Hee University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
South Africa	Charlotte Maxeke Johannesburg Academic Hospital	Parktown, Johannesburg	Gauteng
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Regional de Málaga	Málaga
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Arthur Bloom Haemophilia Centre	Cardiff
United Kingdom	Royal Free Haemophilia Comprehensive Care Center	London
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	UC Denver Hemoph & Thrombo Ctr	Aurora	Colorado
United States	Univ Hosp Cleveland Med Ctr	Cleveland	Ohio
United States	Central Michigan University	Detroit	Michigan
United States	Penn State MS Hershey Med Ctr	Hershey	Pennsylvania
United States	University of Iowa_Iowa City	Iowa City	Iowa
United States	Children's Hosp-Los Angeles	Los Angeles	California
United States	Vanderbilt U Med Ctr_Nashville	Nashville	Tennessee
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,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of treatment-emergent adverse events	Measured as count of events.	From Visit 2 (week 0) until week 26
Secondary	Device handling experience using the Hemophilia Device Handling and Preference Assessment (HDHPA) questionnaire	Measured as percentage of participants. HDHPA measures device handling experience and device preference. The measure consists of 26 items that are reported individually. it is measures in units: Percentage of participants = the distribution of participant answers within each response category, for each of the 26 individual items.	Visit 8 (after 26 weeks of treatment)
Secondary	Change in participants' treatment burden using the Hemophilia treatment experience measure (Hemo-TEM) total score	Measured as score points. Hemo-TEM measures treatment burden. The measure consists of 26 items yielding 5 domain scores and 1 total score. Domain scores (score range): Injection difficulties (0-100), physical impact (0-100), treatment bother (0-100), interference with daily life (0-100), and emotional impact (0-100). Total score ranges 0-100. Higher scores indicate greater treatment burden.	From Visit 2 (week 0) until end of treatment (up to 26 weeks)