Clinical trial NCT04204408: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy Volunteers
Haemophilia A With or Without Inhibitors
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-12-19
Enrollment: 275
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1 placebo-controlled double-blind within cohorts (phase 1) Part 2 open-label (phase 2)
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Part 1: Number of treatment emergent adverse events
timeFrame: From time of dosing (Day 1) to Week 16
measure: Part 2: Number of treatment emergent adverse events
timeFrame: From time of first dosing (Day 1) to Week 12
measure: Part 2, extension: Number of treatment emergent adverse events
timeFrame: From Week 12 up to Week 176 (16 weeks after last dose)
Secondary outcomes:
measure: Part 1: Number of injection site reactions
timeFrame: From time of dosing (Day 1) to Week 16
measure: Part 1: Relative change in D-dimer
timeFrame: From baseline (Day 1) to Week 16
measure: Part 1: Relative change in prothrombin fragment 1 and 2
timeFrame: From baseline (Day 1) to Week 16
measure: Part 1: Relative change in fibrinogen
timeFrame: From baseline (Day 1) to Week 16
measure: Part 1: Relative change in platelets
timeFrame: From baseline (Day 1) to Week 16
measure: Part 1: Cmax, SD: the maximum concentration of Mim8 after a single dose
timeFrame: From baseline (Day 1) to Week 16
measure: Part 1: AUC0-inf, SD: the area under the Mim8 concentration-time curve from time 0 to infinity after a single dose
timeFrame: From baseline (Day 1) to Week 16
measure: Part 1: t1/2, SD: the terminal half-life of Mim8 after a single dose
timeFrame: From baseline (Day 1) to Week 16
measure: Part 1: tmax, SD: the time to maximum concentration of Mim8 after a single dose
timeFrame: From baseline (Day 1) to Week 16
measure: Part 1: Change in activated partial thromboplastin time
timeFrame: From baseline (Day 1) to Week 16
measure: Part 2 (weekly and monthly dosing): Number of injection site reactions
timeFrame: From time of first dosing (Day 1) to Week 12
measure: Part 2 (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies
timeFrame: From baseline (Day 1) to Week 12
measure: Part 2 (weekly and monthly dosing): Relative change in D-dimer
timeFrame: From baseline (Day 1) to Week 12
measure: Part 2 (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2
timeFrame: From baseline (Day 1) to Week 12
measure: Part 2 (weekly and monthly dosing): Relative change in fibrinogen
timeFrame: From baseline (Day 1) to Week 12
measure: Part 2 (weekly and monthly dosing): Relative change in platelets
timeFrame: From baseline (Day 1) to Week 12
measure: Part 2 PK session 2 (weekly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses
timeFrame: From Day 57 to Day 64
measure: Part 2 PK session 2 (weekly dosing): AUCτ, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses
timeFrame: From Day 57 to Day 64
measure: Part 2 PK session 2 (monthly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses
timeFrame: From Day 57 to Day 85
measure: Part 2 PK session 2 (monthly dosing): AUCτ, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses
timeFrame: From Day 57 to Day 85
measure: Part 2 (weekly dosing): Mean of maximum thrombin generation (peak height)
timeFrame: From Day 57 to Day 64
measure: Part 2 (monthly dosing): Mean of maximum thrombin generation (peak height)
timeFrame: From Day 57 to Day 85
measure: Part 2, extension: Number of injection site reactions
timeFrame: From Week 12 up to Week 176 (16 weeks after last dose)
measure: Part 2, extension: Occurrence of anti-Mim8 antibodies
timeFrame: From Week 12 up to Week 176 (16 weeks after last dose)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles - Endocrinology
state: California
city: Chicago
country: United States
facility: Rush University Med. Cntr
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa_Iowa City
state: Iowa
city: Ann Arbor
country: United States
facility: University Of Michigan
state: Michigan
city: Dayton
country: United States
facility: Dayton Children Hemostati Ctr
state: Ohio
city: Innsbruck
country: Austria
facility: Universitätsklinik für Innere Medizin V
city: Sofia
country: Bulgaria
facility: UMHAT "Tsaritsa Yoanna-ISUL"
city: Berlin
country: Germany
facility: Charité Research Organisation GmbH
city: Milano
country: Italy
facility: Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano
state: MI
city: Roma
country: Italy
facility: Policlinico Umberto I Sezione Ematologia
city: Aichi
country: Japan
facility: Nagoya University Hospital_Blood Transfusion
city: Warszawa
country: Poland
facility: Intytut Hematologii i Transfuzjologii
state: Mazowieckie
city: Poznań
country: Poland
facility: Uniwersytecki Szpital Kliniczny W Poznaniu
state: Wielkopolskie
city: Parktown, Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Valencia
country: Spain
facility: Hospital La Fe - Hemostasia y Trombosis
city: Bern
country: Switzerland
facility: Universitätsklinik für Hämatologie
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Edirne
country: Turkey
facility: Trakya University
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: London
country: United Kingdom
facility: Royal Free Haemophilia Comprehensive Care Center
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References: