Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia Without Inhibitors
- Conditions
- Haemophilia B Without InhibitorsHaemophilia A Without Inhibitors
- Interventions
- Registration Number
- NCT04082429
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
This study will test how well a new medicine called concizumab works in the body of people with haemophilia A or B without inhibitors. The purpose is to show that concizumab can prevent bleeds in the body and is safe to use. Participants who usually only take medicine to treat bleeds (on-demand) will be placed in one of two groups. In one group participants will get study medicine from the start of the study. In the other group participants will continue with their normal medicine and get study medicine after 6 months. Which treatment the participant gets is decided by chance. Participants who usually take medicine to prevent bleeds (prophylaxis treatment) or who are already being treated with concizumab (study medicine) will receive the study medicine from the start of the study. Participants will have to inject themselves with the study medicine 1 time every day under the skin. This can be done at home. The study doctor will hand out the medicine in the form of a pen-injector. The pen-injector will contain the study medicine. The study will last for up to 6.5 years. The length of time the participant will be in the study depends on when they agreed to take part or when the medicine is available for purchase in their country (21 April 2026 at the latest). Participants will have to come to the clinic for up to 40 times. The time between visits will be approximately 4 weeks for the first 6 to 12 months depending on the group participants are in, and approximately 8 weeks for the rest of the study. If the participant attends extra visits due to the prescription medicine not being available for purchase in their country, these will be 14 weeks apart. Participants will be asked to record information in an electronic diary during the study and may also be asked to wear an activity tracker.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 156
- 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 years or older at the time of signing informed consent.
- Congenital severe haemophilia A (FVIII below 1%) or B (FIX equal to or below 2%).
- Known or suspected hypersensitivity to any constituent of the trial product or related products.
- Known inherited or acquired coagulation disorder other than congenital haemophilia.
- Presence of confirmed inhibitors 0.6 BU or greater at screening.
- 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.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 3: Concizumab prophylaxis Concizumab The HA patients enrolled into the concizumab phase 2 trial NN7415-4255 (explorer 5) will be offered enrolment into this arm. Arm 2: Concizumab prophylaxis Concizumab HA and HB patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. Arm 1: No prophylaxis (PPX) Concizumab Haemophilia A (HA) and haemophilia B (HB) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. In the extension phase, this group will receive treatment with concizumab. Arm 4: Concizumab prophylaxis Concizumab Arm 4 will include patients previously on prophylaxis with factor products with a minimum of 24 weeks observation in NN7415-4322 (explorer 6) (at least 30 HA and 30 HB patients). In addition, arm 4 will also include: 1) Patients who were randomised to arms 1 and 2 before the treatment pause. 2) HA patients who were in NN7415-4255 (explorer 5) at the time of the treatment pause, and who have now completed explorer 5. 3) On demand patients included after arms 1 and 2 are closed.
- Primary Outcome Measures
Name Time Method For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks) This will be presented as 'count of episodes'.
For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks) This will be presented as 'count of episodes'.
- Secondary Outcome Measures
Name Time Method For haemophilia B patients without inhibitors: Number of treated spontaneous bleeding episodes On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks) This will be presented as 'count of episodes'.
For haemophilia A patients without inhibitors: Number of treated spontaneous bleeding episodes On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks) This will be presented as 'count of episodes'.
For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks) This will be presented as 'count of episodes'.
For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes Time frame is presented under 'outcome measure description' This will be presented as 'count of episodes'. Arm 4 patients who have been on stable PPX at least 24 weeks in study 4322. For previous PPX (study 4322): From the point in time where PPX is stable and up until the end of study. Stable is defined as the time after an initial period on PPX treatment of at least 24 weeks. For concizumab PPX (trial 4307): From the point in time where the concizumab maintenance dose is confirmed, increased or decreased and up until the confirmatory analyses cut-off (at least 24 weeks).
For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes Time frame is presented under 'outcome measure description' This will be presented as 'count of episodes'. Arm 4 patients who have been on stable PPX at least 24 weeks in study 4322. For previous PPX (study 4322): From the point in time where PPX is stable and up until the end of study. Stable is defined as the time after an initial period on PPX treatment of at least 24 weeks. For concizumab PPX (trial 4307): From the point in time where the concizumab maintenance dose is confirmed, increased or decreased and up until the confirmatory analyses cut-off (at least 24 weeks).
For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks) This will be presented as 'count of episodes'.
For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks) This will be presented as 'count of episodes'.
Pre-dose (trough) concizumab plasma concentration (Ctrough) Prior to the concizumab administration at week 24 (after restart) This will be measured in 'ng/mL'.
Pre-dose free tissue factor pathway inhibitor (TFPI) concentration Prior to the concizumab administration at week 24 (after restart) This will be measured in 'ng/mL'.
Number of thromboembolic events Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 296 weeks). This will be presented as 'count of events'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day).
Pre-dose thrombin peak Prior to the concizumab administration at week 24 (after restart) This will be measured in 'nmol/L'.
Maximum concizumab plasma concentration (Cmax) From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart) This will be measured in 'ng/mL'.
For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks) This will be presented as 'count of episodes'.
Number of hypersensitivity type reactions Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 296 weeks). This will be presented as 'count of hypersensitivity type reactions'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day).
Number of injection site reactions Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 296 weeks). This will be presented as 'count of injection site reactions'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day).
Number of patients with antibodies to concizumab Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 296 weeks). This will be presented as 'count of participants'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day).
Area under the concizumab plasma concentration-time curve (AUC) From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart) This will be measured in 'ng\*hr/mL'.
Trial Locations
- Locations (81)
Children's Hospital Los Angeles - Endocrinology
🇺🇸Los Angeles, California, United States
Center for Inherited Blood Disorders
🇺🇸Orange, California, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
M.S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Vanderbilt University Medical Center_Nashville_0
🇺🇸Nashville, Tennessee, United States
University of Texas San Antonio
🇺🇸San Antonio, Texas, United States
Versiti, CCBD
🇺🇸Milwaukee, Wisconsin, United States
Haematology and Blood Bank Department
🇩🇿Algiers, Algeria
CHU Constantine BEN BADIS/ Hematology department
🇩🇿Constantine, Algeria
The Alfred
🇦🇺Melbourne, Victoria, Australia
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