FRONTIER1: A Research Study Investigating Mim8 in People With Haemophilia A

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04204408
• Collaborator: (none)
• Enrollment: 275
• Locations: 28
• Arms: 3
• Anticipated Duration (Months): 61.5
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• 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)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: Jan 10, 2020
• Anticipated Primary Completion Date: Feb 24, 2025
• Anticipated Study Completion Date: Feb 24, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Part 1: Number of treatment emergent adverse events [From time of dosing (Day 1) to Week 16]

   Count

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

   Count

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

   Count

Secondary Outcome Measures

1. Part 1: Number of injection site reactions [From time of dosing (Day 1) to Week 16]

   Count

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

   Percent

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

   Percent

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

   Percent

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

   Percent

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

   Days

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

   Days

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

    Seconds

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

    Count

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

    Count

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

    Percent

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

    Percent

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

    Percent

16. Part 2 (weekly and monthly dosing): Relative change in platelets [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 [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 [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 [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 [From Day 57 to Day 85]

    μg*day/mL

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

    nM

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

    nM

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

    Count

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

    Count

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 64 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Los Angeles	California	United States	90027
2	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60612
3	Novo Nordisk Investigational Site	Iowa City	Iowa	United States	52242
4	Novo Nordisk Investigational Site	Ann Arbor	Michigan	United States	48109
5	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28204
6	Novo Nordisk Investigational Site	Columbus	Ohio	United States	43205
7	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45404
8	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53226
9	Novo Nordisk Investigational Site	Innsbruck		Austria	A 6020
10	Novo Nordisk Investigational Site	Sofia		Bulgaria	1527
11	Novo Nordisk Investigational Site	Berlin		Germany	10117
12	Novo Nordisk Investigational Site	Milano		Italy	20124
13	Novo Nordisk Investigational Site	Roma		Italy	00161
14	Novo Nordisk Investigational Site	Aichi		Japan	466-8560
15	Novo Nordisk Investigational Site	Nara		Japan	634-8522
16	Novo Nordisk Investigational Site	Tokyo		Japan	160-0023
17	Novo Nordisk Investigational Site	Poznań		Poland	60-569
18	Novo Nordisk Investigational Site	Warszawa		Poland	02-776
19	Novo Nordisk Investigational Site	Parktown, Johannesburg	Gauteng	South Africa	2193
20	Novo Nordisk Investigational Site	Madrid		Spain	28046
21	Novo Nordisk Investigational Site	Málaga		Spain	29010
22	Novo Nordisk Investigational Site	Valencia		Spain	46026
23	Novo Nordisk Investigational Site	Bern		Switzerland	3010
24	Novo Nordisk Investigational Site	Ankara		Turkey	06230
25	Novo Nordisk Investigational Site	Edirne		Turkey	22030
26	Novo Nordisk Investigational Site	Izmir		Turkey	35100
27	Novo Nordisk Investigational Site	London		United Kingdom	NW3 2QG
28	Novo Nordisk Investigational Site	Oxford		United Kingdom	OX3 7LJ

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT04204408
• Other Study ID Numbers: NN7769-4513; U1111-1227-4220; 2019-000465-20
• First Posted: Dec 19, 2019
• Last Update Posted: Jun 1, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hemophilia A

Study Results

No Results Posted as of Jun 1, 2022