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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

Tracking Information
First Submitted Date  ICMJE December 17, 2019
First Posted Date  ICMJE December 19, 2019
Last Update Posted Date November 14, 2022
Actual Study Start Date  ICMJE January 10, 2020
Estimated Primary Completion Date February 24, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 27, 2022)
  • Part 1: Number of treatment emergent adverse events [ Time Frame: From time of dosing (Day 1) to Week 16 ]
    Count
  • Part 2: Number of treatment emergent adverse events [ Time Frame: From time of first dosing (Day 1) to Week 12 ]
    Count
  • Part 2, extension: Number of treatment emergent adverse events [ Time Frame: From Week 12 up to Week 176 (16 weeks after last dose) ]
    Count
Original Primary Outcome Measures  ICMJE
 (submitted: December 17, 2019)
  • SAD: Number of treatment emergent adverse events [ Time Frame: From time of dosing (Day 1) to Week 16 ]
    Count
  • MAD: Number of treatment emergent adverse events [ Time Frame: From time of first dosing (Day 1) to Week 12 ]
    Count
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2022)
  • Part 1: Number of injection site reactions [ Time Frame: From time of dosing (Day 1) to Week 16 ]
    Count
  • Part 1: Relative change in D-dimer [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent
  • Part 1: Relative change in prothrombin fragment 1 and 2 [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent
  • Part 1: Relative change in fibrinogen [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent
  • Part 1: Relative change in platelets [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent
  • Part 1: Cmax, SD: the maximum concentration of Mim8 after a single dose [ Time Frame: From baseline (Day 1) to Week 16 ]
    μg/mL
  • 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
  • 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
  • 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
  • Part 1: Change in activated partial thromboplastin time [ Time Frame: From baseline (Day 1) to Week 16 ]
    Seconds
  • Part 2 (weekly and monthly dosing): Number of injection site reactions [ Time Frame: From time of first dosing (Day 1) to Week 12 ]
    Count
  • Part 2 (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies [ Time Frame: From baseline (Day 1) to Week 12 ]
    Count
  • Part 2 (weekly and monthly dosing): Relative change in D-dimer [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent
  • Part 2 (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2 [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent
  • Part 2 (weekly and monthly dosing): Relative change in fibrinogen [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent
  • Part 2 (weekly and monthly dosing): Relative change in platelets [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent
  • 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
  • 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
  • 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
  • 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
  • Part 2 (weekly dosing): Mean of maximum thrombin generation (peak height) [ Time Frame: From Day 57 to Day 64 ]
    nM
  • Part 2 (monthly dosing): Mean of maximum thrombin generation (peak height) [ Time Frame: From Day 57 to Day 85 ]
    nM
  • Part 2, extension: Number of injection site reactions [ Time Frame: From Week 12 up to Week 176 (16 weeks after last dose) ]
    Count
  • Part 2, extension: Occurrence of anti-Mim8 antibodies [ Time Frame: From Week 12 up to Week 176 (16 weeks after last dose) ]
    Count
Original Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2019)
  • SAD: Number of injection site reactions [ Time Frame: From time of dosing (Day 1) to Week 16 ]
    Count
  • SAD: Relative change in D-dimer [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent
  • SAD: Relative change in prothrombin fragment 1 and 2 [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent
  • SAD: Relative change in fibrinogen [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent
  • SAD: Relative change in platelets [ Time Frame: From baseline (Day 1) to Week 16 ]
    Percent
  • SAD: Cmax, SD: the maximum concentration of Mim8 after a single dose [ Time Frame: From baseline (Day 1) to Week 16 ]
    μg/mL
  • SAD: 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
  • SAD: t1/2, SD: the terminal half-life of Mim8 after a single dose [ Time Frame: From baseline (Day 1) to Week 16 ]
    Days
  • SAD: tmax, SD: the time to maximum concentration of Mim8 after a single dose [ Time Frame: From baseline (Day 1) to Week 16 ]
    Days
  • SAD: Change in activated partial thromboplastin time [ Time Frame: From baseline (Day 1) to Week 16 ]
    Seconds
  • MAD (weekly and monthly dosing): Number of injection site reactions [ Time Frame: From time of first dosing (Day 1) to Week 12 ]
    Count
  • MAD (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies [ Time Frame: From baseline (Day 1) to Week 12 ]
    Count
  • MAD (weekly and monthly dosing): Relative change in D-dimer [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent
  • MAD (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2 [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent
  • MAD (weekly and monthly dosing): Relative change in fibrinogen [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent
  • MAD (weekly and monthly dosing): Relative change in platelets [ Time Frame: From baseline (Day 1) to Week 12 ]
    Percent
  • MAD 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
  • MAD 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
  • MAD 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
  • MAD 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
  • MAD (weekly dosing): Mean of maximum thrombin generation (peak height) [ Time Frame: From Day 57 to Day 64 ]
    nM
  • MAD (monthly dosing): Mean of maximum thrombin generation (peak height) [ Time Frame: From Day 57 to Day 85 ]
    nM
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Research Study Investigating Mim8 in People With Haemophilia A
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Healthy Volunteers
  • Haemophilia A With or Without Inhibitors
Intervention  ICMJE
  • 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
  • Drug: Placebo (Mim8)
    Mim8 placebo administered subcutaneously (s.c., under the skin)
Study Arms  ICMJE
  • 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.
    Intervention: Drug: NNC0365-3769 (Mim8)
  • Placebo Comparator: Single dose (part 1) placebo
    Blinded. Single doses in healthy volunteers. In each of the 6 cohorts, 2 participants will receive placebo.
    Intervention: Drug: Placebo (Mim8)
  • 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.
    Intervention: Drug: NNC0365-3769 (Mim8)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 27, 2022)
275
Original Estimated Enrollment  ICMJE
 (submitted: December 17, 2019)
82
Estimated Study Completion Date  ICMJE February 24, 2025
Estimated Primary Completion Date February 24, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Bulgaria,   Germany,   Italy,   Japan,   Poland,   South Africa,   Spain,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04204408
Other Study ID Numbers  ICMJE NN7769-4513
U1111-1227-4220 ( Other Identifier: World Health Organization (WHO) )
2019-000465-20 ( Registry Identifier: European Medicines Agency (EudraCT) )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://novonordisk-trials.com
Current Responsible Party Novo Nordisk A/S
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Novo Nordisk A/S
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Reporting Anchor and Disclosure (1452) Novo Nordisk A/S
PRS Account Novo Nordisk A/S
Verification Date November 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP