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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04204408
Recruitment Status : Active, not recruiting
First Posted : December 19, 2019
Last Update Posted : November 14, 2022
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief 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.


Condition or disease Intervention/treatment Phase
Healthy Volunteers Haemophilia A With or Without Inhibitors Drug: NNC0365-3769 (Mim8) Drug: Placebo (Mim8) Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 275 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Part 1 placebo-controlled double-blind within cohorts (phase 1) Part 2 open-label (phase 2)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Sponsor staff involved in the clinical trial is masked according to company standard procedures
Primary Purpose: Treatment
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
Actual Study Start Date : January 10, 2020
Estimated Primary Completion Date : February 24, 2025
Estimated Study Completion Date : February 24, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hemophilia

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




Primary Outcome Measures :
  1. Part 1: Number of treatment emergent adverse events [ Time Frame: From time of dosing (Day 1) to Week 16 ]
    Count

  2. Part 2: Number of treatment emergent adverse events [ Time Frame: From time of first dosing (Day 1) to Week 12 ]
    Count

  3. Part 2, extension: Number of treatment emergent adverse events [ Time Frame: From Week 12 up to Week 176 (16 weeks after last dose) ]
    Count


Secondary Outcome Measures :
  1. Part 1: Number of injection site reactions [ Time Frame: From time of dosing (Day 1) to Week 16 ]
    Count

  2. Part 1: Relative change in D-dimer [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent

  3. Part 1: Relative change in prothrombin fragment 1 and 2 [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent

  4. Part 1: Relative change in fibrinogen [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent

  5. Part 1: Relative change in platelets [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent

  6. Part 1: Cmax, SD: the maximum concentration of Mim8 after a single dose [ Time Frame: From baseline (Day 1) to Week 16 ]
    μg/mL

  7. Part 1: AUC0-inf, SD: the area under the Mim8 concentration-time curve from time 0 to infinity after a single dose [ Time Frame: From baseline (Day 1) to Week 16 ]
    μg*day/mL

  8. Part 1: t1/2, SD: the terminal half-life of Mim8 after a single dose [ Time Frame: From baseline (Day 1) to Week 16 ]
    Days

  9. Part 1: tmax, SD: the time to maximum concentration of Mim8 after a single dose [ Time Frame: From baseline (Day 1) to Week 16 ]
    Days

  10. Part 1: Change in activated partial thromboplastin time [ Time Frame: From baseline (Day 1) to Week 16 ]
    Seconds

  11. Part 2 (weekly and monthly dosing): Number of injection site reactions [ Time Frame: From time of first dosing (Day 1) to Week 12 ]
    Count

  12. Part 2 (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies [ Time Frame: From baseline (Day 1) to Week 12 ]
    Count

  13. Part 2 (weekly and monthly dosing): Relative change in D-dimer [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent

  14. Part 2 (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2 [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent

  15. Part 2 (weekly and monthly dosing): Relative change in fibrinogen [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent

  16. Part 2 (weekly and monthly dosing): Relative change in platelets [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent

  17. Part 2 PK session 2 (weekly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses [ Time Frame: From Day 57 to Day 64 ]
    μg/mL

  18. Part 2 PK session 2 (weekly dosing): AUCτ, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses [ Time Frame: From Day 57 to Day 64 ]
    μg*day/mL

  19. Part 2 PK session 2 (monthly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses [ Time Frame: From Day 57 to Day 85 ]
    μg/mL

  20. Part 2 PK session 2 (monthly dosing): AUCτ, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses [ Time Frame: From Day 57 to Day 85 ]
    μg*day/mL

  21. Part 2 (weekly dosing): Mean of maximum thrombin generation (peak height) [ Time Frame: From Day 57 to Day 64 ]
    nM

  22. Part 2 (monthly dosing): Mean of maximum thrombin generation (peak height) [ Time Frame: From Day 57 to Day 85 ]
    nM

  23. Part 2, extension: Number of injection site reactions [ Time Frame: From Week 12 up to Week 176 (16 weeks after last dose) ]
    Count

  24. Part 2, extension: Occurrence of anti-Mim8 antibodies [ Time Frame: From Week 12 up to Week 176 (16 weeks after last dose) ]
    Count



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04204408


Locations
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United States, California
Novo Nordisk Investigational Site
Los Angeles, California, United States, 90027
United States, Illinois
Novo Nordisk Investigational Site
Chicago, Illinois, United States, 60612
United States, Iowa
Novo Nordisk Investigational Site
Iowa City, Iowa, United States, 52242
United States, Michigan
Novo Nordisk Investigational Site
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Novo Nordisk Investigational Site
Charlotte, North Carolina, United States, 28204
United States, Ohio
Novo Nordisk Investigational Site
Columbus, Ohio, United States, 43205
Novo Nordisk Investigational Site
Dayton, Ohio, United States, 45404
United States, Wisconsin
Novo Nordisk Investigational Site
Milwaukee, Wisconsin, United States, 53226
Austria
Novo Nordisk Investigational Site
Innsbruck, Austria, A 6020
Bulgaria
Novo Nordisk Investigational Site
Sofia, Bulgaria, 1527
Germany
Novo Nordisk Investigational Site
Berlin, Germany, 10117
Italy
Novo Nordisk Investigational Site
Milano, MI, Italy, 20124
Novo Nordisk Investigational Site
Roma, Italy, 00161
Japan
Novo Nordisk Investigational Site
Aichi, Japan, 466-8560
Poland
Novo Nordisk Investigational Site
Poznań, Poland, 60-569
Novo Nordisk Investigational Site
Warszawa, Poland, 02-776
South Africa
Novo Nordisk Investigational Site
Parktown, Johannesburg, Gauteng, South Africa, 2193
Spain
Novo Nordisk Investigational Site
Madrid, Spain, 28046
Novo Nordisk Investigational Site
Málaga, Spain, 29010
Novo Nordisk Investigational Site
Valencia, Spain, 46026
Switzerland
Novo Nordisk Investigational Site
Bern, Switzerland, 3010
Turkey
Novo Nordisk Investigational Site
Ankara, Turkey, 06230
Novo Nordisk Investigational Site
Edirne, Turkey, 22030
Novo Nordisk Investigational Site
Izmir, Turkey, 35100
United Kingdom
Novo Nordisk Investigational Site
London, United Kingdom, NW3 2QG
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Clinical Reporting Anchor and Disclosure (1452) Novo Nordisk A/S
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT04204408    
Other Study ID Numbers: NN7769-4513
U1111-1227-4220 ( Other Identifier: World Health Organization (WHO) )
2019-000465-20 ( Registry Identifier: European Medicines Agency (EudraCT) )
First Posted: December 19, 2019    Key Record Dates
Last Update Posted: November 14, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn