A Research Study Investigating Mim8 in People With Haemophilia A (FRONTIER1)

Novo Nordisk

Status and phase: Completed; Phase 2

Conditions: Healthy Volunteers; Haemophilia A With or Without Inhibitors

Treatments: Drug: NNC0365-3769 (Mim8); Drug: Placebo (Mim8)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04204408

2019-000465-20 (Registry Identifier)

NN7769-4513

U1111-1227-4220 (Other Identifier)

Details and patient eligibility

About

This study is investigating how Mim8 works in people with haemophilia A, who either have inhibitors or do not have inhibitors. Mim8 is a new medication that will be used for prevention of bleeding episodes. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). Mim8 will be injected with a thin needle in the skin of the stomach, using a pen-injector.

The study will last for up to 44 months. It consists of a main phase (part 1 and part 2) and an extension phase. In part 1, participants will be injected only once with either Mim8 or a "dummy" medicine (placebo) - which one will be decided by chance. In part 2 and the extension phase participants will get an Mim8 injection weekly or monthly.

Enrollment: 275 patients

Sex: Male

Ages: 12+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Single ascending dose part 1:

• Male, aged 18-45 years (both inclusive) at the time of signing informed consent
• Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator

Multiple ascending dose part 2:

• Male, aged 12-64 years (both inclusive) at the time of signing informed consent (Germany and Japan have local requirements)
• Diagnosis of congenital haemophilia A with FVIII activity below 1% based on medical records

Exploratory biomarker cohort:

• Male, aged equal to or above 12 years at the time of signing informed consent (Germany and Japan have local requirements)
• Diagnosis of congenital haemophilia A with FVIII activity below 1% based on medical recordsv

Exclusion criteria

Part 1:

• Factor VIII activity equal to or above 150% at screening
• Increased risk of thrombosis, e.g. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis
• Any clinical signs or established diagnosis of venous or arterial thromboembolic disease

Part 2:

• Known congenital or acquired coagulation disorders other than haemophilia A
• Increased risk of thrombosis as evaluated by the investigator. E.g. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing
• Any clinical signs or established diagnosis of venous or arterial thromboembolic disease with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing
• Advanced atherosclerotic disease (e.g. known history of ischemic heart disease, ischemic stroke) as evaluated by the investigator
• Any autoimmune disease that may increase the risk of thrombosis
• Receipt of emicizumab or drugs with similar modes of action within 5 half-lives before trial product administration
• Ongoing or planned immune tolerance induction therapy

Exploratory biomarker cohort:

• Known congenital or acquired coagulation disorders other than haemophilia A
• Increased risk of thrombosis as evaluated by the investigator. E.g. known history of personal or first degree relative(s) with unprovoked deep vein thrombosis with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing
• Any clinical signs or established diagnosis of venous or arterial thromboembolic disease with exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing
• Advanced atherosclerotic disease (e.g. known history of ischemic heart disease, ischemic stroke) as evaluated by the investigator
• Any autoimmune disease that may increase the risk of thrombosis
• Ongoing or planned immune tolerance induction therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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275 participants in 3 patient groups, including a placebo group

Single dose (part 1) Mim8

Experimental group

Description:

Blinded. Single doses in healthy volunteers. Dose escalation. In each of the 6 cohorts, 6 participants will receive Mim8.

Treatment:

Drug: NNC0365-3769 (Mim8)

Single dose (part 1) placebo

Placebo Comparator group

Description:

Blinded. Single doses in healthy volunteers. In each of the 6 cohorts, 2 participants will receive placebo.

Treatment:

Drug: Placebo (Mim8)

Multiple dose (part 2)

Experimental group

Description:

Open-label. There will be 4 cohorts receiving once-weekly doses (part 2 cohorts 1, 2, 3 and 5) and one cohort receiving once-monthly doses (part 2 cohort 4). Participants will continue into the part 2 extension on the same treatment regimen.

Treatment:

Drug: NNC0365-3769 (Mim8)