A Research Study Investigating Mim8 in People With Haemophilia A

Phase 2

Completed

• Conditions: Haemophilia A With or Without Inhibitors; Healthy Volunteers
• Interventions: Drug: Placebo (Mim8); Drug: NNC0365-3769 (Mim8)

• Registration Number: NCT04204408
• Lead Sponsor: Novo Nordisk A/S

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 available

Study Timeline

• Study First Submitted: 2019-12-17
• Study First Submitted QC: 2019-12-17
• Study First Posted: 2019-12-19
• Study Start: 2020-01-10
• Primary Completion: 2023-10-06
• Study Completion: 2023-10-06
• Status Verified: 2024-10
• Disposition First Submitted: 2024-10-04
• Last Update Submitted: 2024-10-04
• Disposition First Posted: 2024-10-07
• Last Update Posted: 2024-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 275

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Single dose (part 1) placebo	Placebo (Mim8)	Blinded. Single doses in healthy volunteers. In each of the 6 cohorts, 2 participants will receive placebo.
Single dose (part 1) Mim8	NNC0365-3769 (Mim8)	Blinded. Single doses in healthy volunteers. Dose escalation. In each of the 6 cohorts, 6 participants will receive Mim8.
Multiple dose (part 2)	NNC0365-3769 (Mim8)	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.

Primary Outcome Measures

Name	Time	Method
Part 1: Number of treatment emergent adverse events	From time of dosing (Day 1) to Week 16	Count
Part 2: Number of treatment emergent adverse events	From time of first dosing (Day 1) to Week 12	Count
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

Name	Time	Method
Part 2 (weekly and monthly dosing): Relative change in platelets	From baseline (Day 1) to Week 12	Percent
Part 1: Relative change in platelets	From baseline (Day 1) to Week 16	Percent
Part 1: Cmax, SD: the maximum concentration of Mim8 after a single dose	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	From baseline (Day 1) to Week 16	μg\*day/mL
Part 1: Number of injection site reactions	From time of dosing (Day 1) to Week 16	Count
Part 1: Change in activated partial thromboplastin time	From baseline (Day 1) to Week 16	Seconds
Part 2 (weekly and monthly dosing): Number of injection site reactions	From time of first dosing (Day 1) to Week 12	Count
Part 2 (weekly and monthly dosing): Relative change in D-dimer	From baseline (Day 1) to Week 12	Percent
Part 2 (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2	From baseline (Day 1) to Week 12	Percent
Part 1: Relative change in prothrombin fragment 1 and 2	From baseline (Day 1) to Week 16	Percent
Part 1: Relative change in fibrinogen	From baseline (Day 1) to Week 16	Percent
Part 1: t1/2, SD: the terminal half-life of Mim8 after a single dose	From baseline (Day 1) to Week 16	Days
Part 1: Relative change in D-dimer	From baseline (Day 1) to Week 16	Percent
Part 2 (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies	From baseline (Day 1) to Week 12	Count
Part 2 (weekly and monthly dosing): Relative change in fibrinogen	From baseline (Day 1) to Week 12	Percent
Part 1: tmax, SD: the time to maximum concentration of Mim8 after a single dose	From baseline (Day 1) to Week 16	Days
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
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
Part 2 (weekly dosing): Mean of maximum thrombin generation (peak height)	From Day 57 to Day 64	nM
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
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
Part 2 (monthly dosing): Mean of maximum thrombin generation (peak height)	From Day 57 to Day 85	nM
Part 2, extension: Number of injection site reactions	From Week 12 up to Week 176 (16 weeks after last dose)	Count
Part 2, extension: Occurrence of anti-Mim8 antibodies	From Week 12 up to Week 176 (16 weeks after last dose)	Count

Trial Locations

Locations (22)

Children's Hospital Los Angeles - Endocrinology; 🇺🇸 Los Angeles, California, United States

Rush University Med. Cntr; 🇺🇸 Chicago, Illinois, United States

University of Iowa_Iowa City; 🇺🇸 Iowa City, Iowa, United States

University Of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Dayton Children Hemostati Ctr; 🇺🇸 Dayton, Ohio, United States

Universitätsklinik für Innere Medizin V; 🇦🇹 Innsbruck, Austria

UMHAT "Tsaritsa Yoanna-ISUL"; 🇧🇬 Sofia, Bulgaria

Charité Research Organisation GmbH; 🇩🇪 Berlin, Germany

Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano; 🇮🇹 Milano, MI, Italy

Policlinico Umberto I Sezione Ematologia; 🇮🇹 Roma, Italy

Nagoya University Hospital_Blood Transfusion; 🇯🇵 Aichi, Japan

Intytut Hematologii i Transfuzjologii; 🇵🇱 Warszawa, Mazowieckie, Poland

Uniwersytecki Szpital Kliniczny W Poznaniu; 🇵🇱 Poznań, Wielkopolskie, Poland

Charlotte Maxeke Johannesburg Academic Hospital; 🇿🇦 Parktown, Johannesburg, Gauteng, South Africa

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Regional de Málaga; 🇪🇸 Málaga, Spain

Hospital La Fe - Hemostasia y Trombosis; 🇪🇸 Valencia, Spain

Universitätsklinik für Hämatologie; 🇨🇭 Bern, Switzerland

Hacettepe University Medical Faculty; 🇹🇷 Ankara, Turkey

Trakya University; 🇹🇷 Edirne, Turkey

Ege Universitesi Tip Fakultesi; 🇹🇷 Izmir, Turkey

Royal Free Haemophilia Comprehensive Care Center; 🇬🇧 London, United Kingdom