Haemophilia A and B With and Without Inhibitors
Conditions
Brief summary
This study will test how well a new medicine called concizumab works for participants who have haemophilia A or B with or without inhibitors. The purpose is to show that concizumab can prevent bleeds and is safe to use. Participants will have to inject the study medicine every day under the skin with a pen-injector. The study will last for at least 2 years and up to about 4 years. The length of time the participant will be in the study depends on if the study medicine will be available for purchase in their country.
Interventions
DRUGConcizumab
Participants in Arm 1 will be assigned to concizumab prophylaxis starting with a loading dose on treatment day 0 followed by daily injections of an individual maintenance dose. Participants in Arm 2 will be assigned to concizumab prophylaxis with daily injections of an individual maintenance dose.
Sponsors
Novo Nordisk A/S
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Informed consent/assent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study. * Diagnosis of congenital severe haemophilia A (FVIII below 1%) or moderate/severe congenital haemophilia B (FIX (coagulation factor IX) below or equal to 2%), or congenital haemophilia with inhibitors. * For arm 1 only: Male aged below 12 years of age at the time of signing informed consent. * For arm 1 only: Patients with inhibitors (haemophilia A with inhibitors or haemophilia B with inhibitors) 1. Patients with HAwI (haemophilia A with inhibitors) with historical medical records of a total of at least 26 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia \<1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available). 2. Patients with HBwI (haemophilia B with inhibitors) with historical medical records of a total of at least 26 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia \<1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available). 3. Patients with HBwI regardless of the regimen and duration of previous haemophilia treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) * For arm 1 only: Patients without inhibitors (haemophilia A or haemophilia B) 1. Patients with historical medical records of at least 52 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products; Surgery related PPX or short-term PPX (e.g., in relation to a severe bleed) is not allowed) during the last year prior to enrolment and with at least 3 documented treated bleeds (For participants less than (\<) 2 years of age there is no limitation for number of documented treated bleeds in the medical history) during this period 2. Patients with historical medical records of a total of at least 26 weeks of PPX (prophylaxis) treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia \<1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available) * For arm 2 only: Male patients (regardless of age) previously treated with concizumab via compassionate use.
Exclusion criteria
* Known or suspected hypersensitivity to study intervention or related products. * Known inherited or acquired coagulation disorder other than congenital haemophilia. * Ongoing or planned Immune Tolerance Induction treatment. * History of thromboembolic disease (aIncludes arterial and venous thrombosis including myocardial infarction, pulmonary embolism, cerebral infarction/thrombosis, deep vein thrombosis, other clinically significant thromboembolic events and peripheral artery occlusion.). Current clinical signs of or treatment for thromboembolic disease. Patients who in the judgement of the investigator are considered at high risk of thromboembolic events (Thromboembolic risk factors could include, but are not limited to, hypercholesterolemia, diabetes mellitus, hypertension, obesity, smoking, family history of thromboembolic events, arteriosclerosis, other conditions associated with increased risk of thromboembolic events).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients treated on demand during at least the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target joints | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| Concizumab-naïve pateints - Number of treatment emergent adverse events, reported both separately for inhibitor and non-inhibitor patients and combined | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of event(s) |
| Number of thromboembolic events, reported both separately for inhibitor and non-inhibitor patients and combined | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of event(s) |
| Number of hypersensitivity type reactions, reported both separately for inhibitor and non-inhibitor patients and combined | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of event(s) |
| Number of injection site reactions, reported both separately for inhibitor and non-inhibitor patients and combined | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of event(s) |
| Number of patients who develop antibodies to concizumab - yes/no, reported both separately for inhibitor and non-inhibitor patients and combined | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of patient(s) |
| Number of treatment emergent adverse events, reported both separately for inhibitor and non-inhibitor patients and combined | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of event(s) |
| Concizumab plasma concentrations prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined | Week 32 | Measured in ng/mL |
| Peak thrombin generation prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined | Week 32 | Measured in nM |
| Free TFPI concentration prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined | Week 32 | Measured in ng/mL |
| Pre-dose (trough) concizumab plasma concentration (Ctrough), reported both separately for inhibitor and non-inhibitor patients and combined | Prior to the concizumab administration at week 20 | Measured in ng/mL |
| Maximum concizumab plasma concentration (Cmax), reported both separately for inhibitor and non-inhibitor patients and combined | From 0 to 24 hours where 0 is the time of the concizumab dose at week 20 | Measured in ng/mL |
| Area under the concizumab plasma concentration-time curve (AUC), reported both separately for inhibitor and non-inhibitor patients and combined | From 0 to 24 hours where 0 is the time of the concizumab dose at week 20 | Measured in ng\*hr/mL |
| For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic) | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated joint bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target joints | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients treated on-demand during at least the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic) | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients treated on-demand during at least the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients treated on-demand at least the last 52 weeks prior enrolment: Number of treated joint bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients treated on-demand at least the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target joints | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic) | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
| For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated joint bleeding episodes | From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks) | Count of episode(s) |
Countries
Algeria, Bosnia and Herzegovina, Bulgaria, Canada, Estonia, France, Greece, India, Italy, Japan, Lebanon, Lithuania, Malaysia, North Macedonia, Norway, Poland, Romania, South Africa, Spain, Sweden, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Transparency (dept. 2834)
Novo Nordisk A/S
Outcome results
None listed