A Research Study Investigating Mim8 in People With Haemophilia A

Healthy Volunteers Clinical Trial

— FRONTIER1  

Official title:

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Subcutaneous Doses of NNC0365-3769 (Mim8) in Healthy Subjects and in Subjects With Haemophilia A With or Without Factor VIII Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04204408
• Other study ID #: NN7769-4513
• Secondary ID: U1111-1227-42202
• Status: Completed
• Phase: Phase 2
• Start date: January 10, 2020
• Est. completion date: October 6, 2023

Study information

• Verified date: November 2023
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 275
• Est. completion date: October 6, 2023
• Est. primary completion date: October 6, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 12 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Haemophilia A With or Without Inhibitors
• Healthy Volunteers
• Hemophilia A

Intervention

Drug:
• NNC0365-3769 (Mim8)
Mim8 administered subcutaneously (s.c., under the skin). The treatment period will consist of 12 once-weekly doses or 3 once-monthly doses
• Placebo (Mim8)
Mim8 placebo administered subcutaneously (s.c., under the skin)

Locations

Country	Name	City	State
Austria	Novo Nordisk Investigational Site	Innsbruck
Bulgaria	Novo Nordisk Investigational Site	Sofia
Germany	Novo Nordisk Investigational Site	Berlin
Italy	Novo Nordisk Investigational Site	Milano	MI
Italy	Novo Nordisk Investigational Site	Roma
Japan	Novo Nordisk Investigational Site	Aichi
Poland	Novo Nordisk Investigational Site	Poznan	Wielkopolskie
Poland	Novo Nordisk Investigational Site	Warszawa	Mazowieckie
South Africa	Novo Nordisk Investigational Site	Parktown, Johannesburg	Gauteng
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Málaga
Spain	Novo Nordisk Investigational Site	Valencia
Switzerland	Novo Nordisk Investigational Site	Bern
Turkey	Novo Nordisk Investigational Site	Ankara
Turkey	Novo Nordisk Investigational Site	Edirne
Turkey	Novo Nordisk Investigational Site	Izmir
United Kingdom	Novo Nordisk Investigational Site	London
United States	Novo Nordisk Investigational Site	Ann Arbor	Michigan
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	Iowa City	Iowa
United States	Novo Nordisk Investigational Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  Germany,  Italy,  Japan,  Poland,  South Africa,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of treatment emergent adverse events	Count	From time of dosing (Day 1) to Week 16
Primary	Part 2: Number of treatment emergent adverse events	Count	From time of first dosing (Day 1) to Week 12
Primary	Part 2, extension: Number of treatment emergent adverse events	Count	From Week 12 up to Week 176 (16 weeks after last dose)
Secondary	Part 1: Number of injection site reactions	Count	From time of dosing (Day 1) to Week 16
Secondary	Part 1: Relative change in D-dimer	Percent	From baseline (Day 1) to Week 16
Secondary	Part 1: Relative change in prothrombin fragment 1 and 2	Percent	From baseline (Day 1) to Week 16
Secondary	Part 1: Relative change in fibrinogen	Percent	From baseline (Day 1) to Week 16
Secondary	Part 1: Relative change in platelets	Percent	From baseline (Day 1) to Week 16
Secondary	Part 1: Cmax, SD: the maximum concentration of Mim8 after a single dose	µg/mL	From baseline (Day 1) to Week 16
Secondary	Part 1: AUC0-inf, SD: the area under the Mim8 concentration-time curve from time 0 to infinity after a single dose	µg*day/mL	From baseline (Day 1) to Week 16
Secondary	Part 1: t1/2, SD: the terminal half-life of Mim8 after a single dose	Days	From baseline (Day 1) to Week 16
Secondary	Part 1: tmax, SD: the time to maximum concentration of Mim8 after a single dose	Days	From baseline (Day 1) to Week 16
Secondary	Part 1: Change in activated partial thromboplastin time	Seconds	From baseline (Day 1) to Week 16
Secondary	Part 2 (weekly and monthly dosing): Number of injection site reactions	Count	From time of first dosing (Day 1) to Week 12
Secondary	Part 2 (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies	Count	From baseline (Day 1) to Week 12
Secondary	Part 2 (weekly and monthly dosing): Relative change in D-dimer	Percent	From baseline (Day 1) to Week 12
Secondary	Part 2 (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2	Percent	From baseline (Day 1) to Week 12
Secondary	Part 2 (weekly and monthly dosing): Relative change in fibrinogen	Percent	From baseline (Day 1) to Week 12
Secondary	Part 2 (weekly and monthly dosing): Relative change in platelets	Percent	From baseline (Day 1) to Week 12
Secondary	Part 2 PK session 2 (weekly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses	µg/mL	From Day 57 to Day 64
Secondary	Part 2 PK session 2 (weekly dosing): AUCt, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses	µg*day/mL	From Day 57 to Day 64
Secondary	Part 2 PK session 2 (monthly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses	µg/mL	From Day 57 to Day 85
Secondary	Part 2 PK session 2 (monthly dosing): AUCt, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses	µg*day/mL	From Day 57 to Day 85
Secondary	Part 2 (weekly dosing): Mean of maximum thrombin generation (peak height)	nM	From Day 57 to Day 64
Secondary	Part 2 (monthly dosing): Mean of maximum thrombin generation (peak height)	nM	From Day 57 to Day 85
Secondary	Part 2, extension: Number of injection site reactions	Count	From Week 12 up to Week 176 (16 weeks after last dose)
Secondary	Part 2, extension: Occurrence of anti-Mim8 antibodies	Count	From Week 12 up to Week 176 (16 weeks after last dose)