Haemophilia A with inhibitors Haemophilia B with inhibitors MedDRA version: 20.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: LLT Classification code 10053752 Term: Hemophilia B with anti factor IX System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male aged 12 or older years at the time of signing informed consent - Congenital Haemophilia A or B of any severity with documented history of inhibitor (0.6 BU or more) - Patient has been prescribed, or in need of, treatment with bypassing agents in the last 24 weeks prior to screening (for patients not previously enrolled in NN7415-4310 (explorer 4)) Are the trial subjects under 18? yes Number of subjects for this age range: 15 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 96 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Known or suspected hypersensitivity to any constituent of the trial product or related products - Known inherited or acquired coagulation disorder other than congenital haemophilia - Ongoing or planned Immune Tolerance Induction treatment - History of thromboembolic disease (includes 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 |
|---|---|
| Main Objective: To compare effect of concizumab prophylaxis to no prophylaxis (on-demand treatment with bypassing agents) in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia A or B with inhibitors;Secondary Objective: 1. To compare the patient reported outcomes (PROs) after treatment with concizumab prophylaxis vs no prophylaxis in adult and adolescent patients with haemophilia A or B with inhibitors 2. To investigate the safety of concizumab prophylaxis in adult and adolescent patients with haemophilia A or B with inhibitors 3. To investigate the PK and PD parameters of concizumab prophylaxis in adult and adolescent patients with haemophilia A or B with inhibitors;Primary end point(s): The number of treated spontaneous and traumatic bleeding episodes;Timepoint(s) of evaluation of this end point: On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in 36 Item short form health survey version 2 (SF36v2) bodily pain 2. Change in SF36v2 physical functioning 3. Number of treated spontaneous bleeding episodes 4. Number of treated spontaneous and traumatic joint bleeds 5. Number of treated spontaneous and traumatic target joint bleeds 6. Number of thromboembolic events 7. Number of thromboembolic events 8. Number of hypersensitivity type reactions 9. Number of hypersensitivity type reactions 10. Number of injection site reactions 11. Number of injection site reactions 12. Number of patients with antibodies to concizumab 13. Number of patients with antibodies to concizumab 14. Pre-dose (trough) concizumab plasma concentration (Ctrough) 15. Pre-dose thrombin peak 16. Pre-dose free tissue factor pathway inhibitor (TFPI) concentration 17. Maximum concizumab plasma concentration (Cmax) 18. Area under the concizumab plasma concentration-time curve (AUC);Timepoint(s) of evaluation of this end point: 1-2:treatment (Trt.) start (week (wk) 0), wk24 3-5:On demand (OD) (arm 1): Randomisation (wk0) to dose start (min. 24 wks) Concizumab (Conci.) (arm 2): new dosing start (wk0) to primary analysis cut-off (min. 32 wks) 6, 8 &10: OD (arm 1 main part): -Randomisation to OD Trt. to start of dose 6, 8, 10 & 12: Conci. (arms 2-4): -Before pause: Trt. start (wk0) to 7 wks after Trt. pause -After pause: dose start (wk0) to primary analysis cut-off (min. 32 wks) Conci. (arm 1 ext. part): new dosing start (wk25) to the primary analysis cut-off 7, 9, 11 & 13: Conci.: -Before pause: Trt. start (wk0) to 7 wks after Trt. pause -After pause: dose start to end of trial (up to 280 weeks) 14-16:Prior to dose at wk24 (after restart) 17-18:0-24 hrs (0: time of dose at wk24 (after restart)) | — |
Countries
Algeria, Australia, Austria, Bulgaria, Croatia, Czech Republic, Denmark, European Union, France, India, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Norway, Poland, Portugal, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Türkiye, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Transparency (2834)
Novo Nordisk A/S
Outcome results
None listed