Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Research Study of How a New Medicine NNC0365-3769 (Mim8) Works in the Body of Healthy People and Patients With Bleeding Disorder (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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04204408
Recruitment Status : Recruiting
First Posted : December 19, 2019
Last Update Posted : April 6, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Brief Summary:
This study consists of 2 parts. Part 1 looks at the safety and tolerability when the study medicine Mim8 is given to healthy subjects for the first time. The obtained results will help to perform a second part of the study with patients who suffer from a bleeding disorder called haemophilia A. Haemophilia A is an inherited condition caused by a lack of a protein called factor VIII. Mim8 works in the body for a longer time than most other products used by patients with haemophilia A. Mim8 is designed for once weekly or once monthly administration. In Part 1, participants will be injected only once with either Mim8 or a "dummy" medicine (placebo) under the tummy skin - which one will be decided by chance. In this study, Mim8 will be used for the first time in humans. Mim8 is a new medicine and cannot be prescribed by doctors in any country. Mim8 belongs to a group of medicines called antibodies. Mim8 is designed to take over the function of the missing factor VIII in haemophilia A patients. Part 1 of the study will last for up to 20 weeks. Participants will attend a screening visit, followed by a 12-day in-house visit where they will have to stay in the study unit. This is followed by 10 ambulatory visits with the study doctor throughout the remaining part of the study. Assessments will include several blood tests and electrocardiograms (ECGs). In part 2 of the study, people with haemophilia A - with or without inhibitors - will be given injections with a thin needle in the skin of their stomach, either weekly or monthly. Part 2 of the study will last for 28 or 31 weeks. This depends on whether the study medicine is given weekly or monthly. Participants will have either 19 or 22 visits with the doctor. The number of visits depends on whether the study medicine is given weekly or monthly. Participants will hear more about which other medicines they can use while they are in the study. Participants will fill in a diary between visits.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 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 : March 9, 2021
Estimated Study Completion Date : August 5, 2021

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 5 cohorts, 6 participants will receive Mim8.
Drug: NNC0365-3769 A (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 5 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 3 cohorts receiving once-weekly doses (part 2 cohorts 1, 2 and 3) and one cohort receiving once-monthly doses (part 2 cohort 4).
Drug: NNC0365-3769 A (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


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



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.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 64 Years   (Child, 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


Contacts
Layout table for location contacts
Contact: Novo Nordisk (+1) 866-867-7178 clinicaltrials@novonordisk.com

Locations
Layout table for location information
Germany
Novo Nordisk Investigational Site Recruiting
Berlin, Germany, 10117
Poland
Novo Nordisk Investigational Site Not yet recruiting
Warszawa, Poland, 02-776
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Layout table for investigator information
Study Director: Clinical Reporting Anchor and Disclosure (1452) Novo Nordisk A/S

Layout table for additonal information
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: April 6, 2020
Last Verified: April 2020
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

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