A study examining the mechanism of action of a new drug NNC0365-3769 (Mim8) in the body of healthy subjects and in patients with hemophilia A
Résumé de l'étude
In this study, a new drug is being investigated in patients with hemophilia A. It is the antibody NNC0365-3769, also known as Mim8. Mim8 belongs to a group of drugs called antibodies. Mim8 is intended to replace the function of the missing factor VIII in patients with hemophilia A. Hemophilia A is a hereditary condition caused by the absence of a protein called factor VIII. The aim of the study is to investigate the safety, tolerability, and efficacy of single or multiple injections of the Mim8 antibody in patients with severe hemophilia A. The first part of the study to verify the safety and tolerability of the study drug will first be conducted in healthy subjects only in Germany. The second part of the study consists of a part called MAD (multiple ascending doses) and a biomarker part. The MAD part will then transition into an extension phase. In this MAD part, study participants with severe hemophilia A will be divided into four groups to investigate the safety, tolerability, and efficacy of either weekly or monthly injections. This part of the study will be conducted at multiple study centers worldwide.
(BASEC)
Intervention étudiée
The MAD part of the study will last 24 or 27 weeks. The duration of the study depends on whether the study drug is administered weekly or monthly. Overall, this part of the study includes 18 or 21 visits to the study center. The number of visits also depends on whether the study drug is administered weekly or monthly. After the completion of the MAD part, the patient will have the option to transition to an extension phase, which includes up to 16 visits. Together with the MAD part, the total study duration is 120 weeks.
Additionally, hemophilia A patients will be separately included in the study to investigate various laboratory markers (biomarker cohort). The biomarker group is necessary to generate data that will be used for the evaluation of Mim8. Patients will participate in 5 visits to the study center and the total study duration will be 16 weeks.
During the visits to the study center, the study drug will be administered to the patient, except in the extension phase, where the patient self-injects the study drug. Additionally, various assessments (e.g., height, weight, electrocardiogram) will be performed, and blood samples will be taken. Study participants will also be required to keep a diary between visits.
(BASEC)
Maladie en cours d'investigation
Hemophilia A
(BASEC)
MAD Phase: 1. Male patients aged 18 to 64 years at the time of signing the informed consent form. 2. Diagnosis of congenital hemophilia A with an FVIII activity of less than 1% based on medical records. Biomarker Cohort: 1. Male patients who are at least 18 years old at the time of signing the informed consent form. 2. Diagnosis of congenital hemophilia A with an FVIII activity of less than 1% based on medical records. (BASEC)
Critères d'exclusion
MAD Phase and Biomarker Cohort: 1. Known congenital or acquired coagulation disorders other than hemophilia A. 2. Increased risk of thrombosis, e.g., personally known history or relatives (first degree) with deep vein thrombosis (formation of a blood clot in the veins). 3. Any clinical signs or proven diagnosis of a thromboembolic disease (formation of blood clots in blood vessels). 4. Advanced atherosclerotic disease (e.g., known history of heart disease or stroke). 5. Receipt of Emicizumab or drugs with similar mechanisms of action prior to administration of the study drug (only in the MAD phase). (BASEC)
Lieu de l’étude
Berne
(BASEC)
Sponsor
non disponible
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Abteilung Klinische Studien
+41 44 914 11 11
IO-NWE-CH-Clinical@clutternovonordisk.com(BASEC)
Informations générales
Novo Nordisk A/S
(ICTRP)
Informations scientifiques
Novo Nordisk A/S
(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique de Berne
(BASEC)
Date d'approbation du comité d'éthique
11.06.2020
(BASEC)
Identifiant de l'essai ICTRP
NCT04204408 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
non disponible
Titre académique
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 (ICTRP)
Titre public
A Research Study Investigating Mim8 in People With Haemophilia A (ICTRP)
Maladie en cours d'investigation
Healthy Volunteers;Haemophilia A With or Without Inhibitors (ICTRP)
Intervention étudiée
Drug: NNC0365-3769 (Mim8);Drug: Placebo (Mim8) (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Critères d'inclusion/exclusion
Gender: Male
Maximum age: N/A
Minimum age: 12 Years
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 (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Part 1: Number of treatment emergent adverse events;Part 2: Number of treatment emergent adverse events;Part 2, extension: Number of treatment emergent adverse events (ICTRP)
Part 1: Number of injection site reactions;Part 1: Relative change in D-dimer;Part 1: Relative change in prothrombin fragment 1 and 2;Part 1: Relative change in fibrinogen;Part 1: Relative change in platelets;Part 1: Cmax, SD: the maximum concentration of Mim8 after a single dose;Part 1: AUC0-inf, SD: the area under the Mim8 concentration-time curve from time 0 to infinity after a single dose;Part 1: t1/2, SD: the terminal half-life of Mim8 after a single dose;Part 1: tmax, SD: the time to maximum concentration of Mim8 after a single dose;Part 1: Change in activated partial thromboplastin time;Part 2 (weekly and monthly dosing): Number of injection site reactions;Part 2 (weekly and monthly dosing): Occurrence of anti-Mim8 antibodies;Part 2 (weekly and monthly dosing): Relative change in D-dimer;Part 2 (weekly and monthly dosing): Relative change in prothrombin fragment 1 and 2;Part 2 (weekly and monthly dosing): Relative change in fibrinogen;Part 2 (weekly and monthly dosing): Relative change in platelets;Part 2 PK session 2 (weekly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses;Part 2 PK session 2 (weekly dosing): AUCt, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses;Part 2 PK session 2 (monthly dosing): Cmax, MD: the maximum concentration of Mim8 after multiple doses;Part 2 PK session 2 (monthly dosing): AUCt, MD: the area under the Mim8 concentration-time curve in the dosing interval after multiple doses;Part 2 (weekly dosing): Mean of maximum thrombin generation (peak height);Part 2 (monthly dosing): Mean of maximum thrombin generation (peak height);Part 2, extension: Number of injection site reactions;Part 2, extension: Occurrence of anti-Mim8 antibodies (ICTRP)
Date d'enregistrement
17.12.2019 (ICTRP)
Inclusion du premier participant
non disponible
Sponsors secondaires
non disponible
Contacts supplémentaires
Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S (ICTRP)
ID secondaires
U1111-1227-4220, 2019-000465-20, NN7769-4513 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT04204408 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible