A Research Study Investigating Mim8 in People With Haemophilia A (FRONTIER1)
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| ClinicalTrials.gov Identifier: NCT04204408 |
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Recruitment Status :
Active, not recruiting
First Posted : December 19, 2019
Last Update Posted : November 14, 2022
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Sponsor:
Novo Nordisk A/S
Information provided by (Responsible Party):
Novo Nordisk A/S
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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 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 Genetics related topics:
Hemophilia
MedlinePlus related topics:
Hemophilia
| Arm | Intervention/treatment |
|---|---|
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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.
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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 |
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Placebo Comparator: Single dose (part 1) placebo
Blinded. Single doses in healthy volunteers. In each of the 6 cohorts, 2 participants will receive placebo.
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Drug: Placebo (Mim8)
Mim8 placebo administered subcutaneously (s.c., under the skin) |
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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.
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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 :
- 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
Secondary Outcome Measures :
- 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
Information from the National Library of Medicine
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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
| 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
| Study Director: | Clinical Reporting Anchor and Disclosure (1452) | Novo Nordisk A/S |
| 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 |
| 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 |