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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Haemophilia A With or Without Inhibitors
• Intervention / Treatment: Drug: NNC0365-3769 (Mim8); Drug: Placebo (Mim8)

• Study Type: Interventional
• Enrollment (Actual): 275
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, A 6020
    • Novo Nordisk Investigational Site
• Bulgaria
  • Sofia, Bulgaria, 1527
    • Novo Nordisk Investigational Site
• Germany
  • Berlin, Germany, 10117
    • Novo Nordisk Investigational Site
• Italy
  • Roma, Italy, 00161
    • Novo Nordisk Investigational Site
  • MI
    • Milano, MI, Italy, 20124
      • Novo Nordisk Investigational Site
• Japan
  • Aichi, Japan, 466-8560
    • Novo Nordisk Investigational Site
• Poland
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-776
      • Novo Nordisk Investigational Site
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-569
      • Novo Nordisk Investigational Site
• South Africa
  • Gauteng
    • Parktown, Johannesburg, Gauteng, South Africa, 2193
      • Novo Nordisk Investigational Site
• Spain
  • Madrid, Spain, 28046
    • Novo Nordisk Investigational Site
  • Málaga, Spain, 29010
    • Novo Nordisk Investigational Site
  • Valencia, Spain, 46026
    • Novo Nordisk Investigational Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novo Nordisk Investigational Site
• Turkey
  • Ankara, Turkey, 06230
    • Novo Nordisk Investigational Site
  • Edirne, Turkey, 22030
    • Novo Nordisk Investigational Site
  • Izmir, Turkey, 35100
    • Novo Nordisk Investigational Site
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Novo Nordisk Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Novo Nordisk Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novo Nordisk Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Novo Nordisk Investigational Site
  • Ohio
    • Dayton, Ohio, United States, 45404
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose (part 1) Mim8; Blinded. Single doses in healthy volunteers. Dose escalation. In each of the 6 cohorts, 6 participants will receive Mim8.	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 Comparator: Single dose (part 1) placebo; Blinded. Single doses in healthy volunteers. In each of the 6 cohorts, 2 participants will receive placebo.	Drug: Placebo (Mim8); Mim8 placebo administered subcutaneously (s.c., under the skin)
Experimental: Multiple dose (part 2); 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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of treatment emergent adverse events	Count	From time of dosing (Day 1) to Week 16
Part 2: Number of treatment emergent adverse events	Count	From time of first dosing (Day 1) to Week 12
Part 2, extension: Number of treatment emergent adverse events	Count	From Week 12 up to Week 176 (16 weeks after last dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of injection site reactions	Count	From time of dosing (Day 1) to Week 16
Part 1: Relative change in D-dimer	Percent	From baseline (Day 1) to Week 16
Part 1: Relative change in prothrombin fragment 1 and 2	Percent	From baseline (Day 1) to Week 16
Part 1: Relative change in fibrinogen	Percent	From baseline (Day 1) to Week 16
Part 1: Relative change in platelets	Percent	From baseline (Day 1) to Week 16
Part 1: Cmax, SD: the maximum concentration of Mim8 after a single dose	μg/mL	From baseline (Day 1) to Week 16
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
Part 1: t1/2, SD: the terminal half-life of Mim8 after a single dose	Days	From baseline (Day 1) to Week 16
Part 1: tmax, SD: the time to maximum concentration of Mim8 after a single dose	Days	From baseline (Day 1) to Week 16
Part 1: Change in activated partial thromboplastin time	Seconds	From baseline (Day 1) to Week 16
Part 2 (weekly and monthly dosing): Number of injection site reactions	Count	From time of first dosing (Day 1) to Week 12
Part 2 (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies	Count	From baseline (Day 1) to Week 12
Part 2 (weekly and monthly dosing): Relative change in D-dimer	Percent	From baseline (Day 1) to Week 12
Part 2 (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2	Percent	From baseline (Day 1) to Week 12
Part 2 (weekly and monthly dosing): Relative change in fibrinogen	Percent	From baseline (Day 1) to Week 12
Part 2 (weekly and monthly dosing): Relative change in platelets	Percent	From baseline (Day 1) to Week 12
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
Part 2 PK session 2 (weekly dosing): AUCτ, 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
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
Part 2 PK session 2 (monthly dosing): AUCτ, 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
Part 2 (weekly dosing): Mean of maximum thrombin generation (peak height)	nM	From Day 57 to Day 64
Part 2 (monthly dosing): Mean of maximum thrombin generation (peak height)	nM	From Day 57 to Day 85
Part 2, extension: Number of injection site reactions	Count	From Week 12 up to Week 176 (16 weeks after last dose)
Part 2, extension: Occurrence of anti-Mim8 antibodies	Count	From Week 12 up to Week 176 (16 weeks after last dose)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2020
• Primary Completion (Actual): October 6, 2023
• Study Completion (Actual): October 6, 2023

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 17, 2019
• First Posted (Actual): December 19, 2019

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 5, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: NN7769-4513; U1111-1227-4220 (Other Identifier: World Health Organization (WHO)); 2019-000465-20 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No