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

• ClinicalTrials.gov Identifier: NCT04204408
• Recruitment Status: Active, not recruiting
• First Posted: December 19, 2019
• Last Update Posted: November 14, 2022
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: December 17, 2019
• First Posted Date: December 19, 2019
• Last Update Posted Date: November 14, 2022
• Actual Study Start Date: January 10, 2020
• Estimated Primary Completion Date: February 24, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: A Research Study Investigating Mim8 in People With Haemophilia A
• 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

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: Interventional
• Study Phase: Phase 2

Study Design

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

• Healthy Volunteers
• Haemophilia A With or Without Inhibitors

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
• Drug: Placebo (Mim8)
  Mim8 placebo administered subcutaneously (s.c., under the skin)

Study Arms

• 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

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 27, 2022): 275
• Original Estimated Enrollment (submitted: December 17, 2019): 82
• Estimated Study Completion Date: February 24, 2025
• Estimated Primary Completion Date: February 24, 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Bulgaria, Germany, Italy, Japan, Poland, South Africa, Spain, Switzerland, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: 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) )
• 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

• 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: Novo Nordisk A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Novo Nordisk A/S
• Verification Date: November 2022