A research study looking at how safe it is to switch from emicizumab to Mim8 in people with haemophilia A (FRONTIER 5).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

21 Jul 2023 → 20 Jul 2024

Decision date (initial)

2023-06-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novo Nordiks A/S

External identifiers

EU CT number

2022-502450-13-00

WHO UTN

U1111-1281-9323

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Safety

To evaluate the safety of Mim8 prophylaxis during emicizumab washout in adults and adolescents with haemophilia A with or without FVIII inhibitors who have switched directly from prophylaxis with emicizumab.

Secondary objectives 2

1. To evaluate the device handling experience for administration of Mim8 using the DV3407-C1 pen-injector.
2. To evaluate the treatment burden with Mim8 prophylaxis in adults and adolescents with haemophilia A with or without FVIII inhibitors who have switched directly from prophylaxis with emicizumab.

Conditions and MedDRA coding

Haemophilia A with or without coagulation factor VIII (FVIII) inhibitors.

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, National Medical Products Administration, Health Products Regulatory Authority, Health Canada, Pharmaceuticals And Medical Devices Agency, Paul Ehrlich Institute, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002762-PIP02-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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.
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. Patients treated with emicizumab QW, Q2W, or Q4W according to the label for at least 8 weeks prior to screening.
5. Patients for whom the decision to discontinue emicizumab treatment has been made.
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.

Exclusion criteria 15

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 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 eventsa (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) >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) ≤30 mL/min/1.73 m2 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of treatment-emergent adverse events (TEAEs).

Secondary endpoints 2

1. Device handling experience using haemophilia device assessment tool (H-DAT) questionnaire.
2. Change in participants’ treatment burden using the haemophilia treatment experience measure (Hemo-TEM) total score.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 6

Locations

6 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 20 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications