Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B Without Inhibitors
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- Novo Nordisk A/S
- Enrollment
- 156
- Locations
- 173
- Primary Endpoint
- Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Study Overview
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 8 years. The length of time the participant will be in the study depends on when they agreed to take part and when the medicine is available for purchase in their country (or 31 December 2027 at the latest). 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 12 Years to — (Child, Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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 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%).
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.
- •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.)
Arms & Interventions
Arm 2: Concizumab prophylaxis
HA and HB patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.
Intervention: Concizumab (Drug)
Arm 3: Concizumab prophylaxis
The HA patients enrolled into the concizumab phase 2 trial NN7415-4255 (explorer 5) will be offered enrolment into this arm.
Intervention: Concizumab (Drug)
Arm 1: No prophylaxis (PPX)
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.
Intervention: Concizumab (Drug)
Arm 4: Concizumab prophylaxis
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.
Intervention: Concizumab (Drug)
Outcomes
Primary Outcomes
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Time Frame: On demand (arm 1): From week 0 up until start of concizumab treatment (week 24); Concizumab (arm 2): From week 0 up until the confirmatory analyses cut-off
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment without ancillary therapy excluding data before restart (OTwoATexBR). It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of annualised bleeding rate (ABR). Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Time Frame: On demand (arm 1): From week 0 up until start of concizumab treatment (week 24); Concizumab (arm 2): From week 0 up until the confirmatory analyses cut-off
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.
Secondary Outcomes
- Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes(For previous PPX (study 4322): After an initial period on PPX treatment of at least 24 weeks until end of study (maximum 115 weeks) For concizumab PPX (trial 4307): After an initial 5-8 weeks dose adjustment period and up until 56 week cut off)
- Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes(For previous PPX (study 4322): After an initial period on PPX treatment of at least 24 weeks until end of study (maximum 115 weeks) For concizumab PPX (trial 4307): After an initial 5-8 weeks dose adjustment period and up until 56 week cut off)
- Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes(On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off)
- Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes(On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off)
- Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes(On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off)
- Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes(On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off)
- Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Target Joint Bleeding Episodes(On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off)
- Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Target Joint Bleeding Episodes(On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off)
- Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Thromboembolic Events(From week 0 to end of trial (up to 384 weeks))
- Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Hypersensitivity Type Reactions(From week 0 to end of trial (up until 384 weeks))
- Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Injection Site Reactions(From week 0 to end of trial (up until 384 weeks))
- Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Participants With Antibodies to Concizumab(From week 0 to end of trial (up until 384 weeks))
- Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose (Trough) Concizumab Plasma Concentration (Ctrough)(Pre-dose (prior to the concizumab administration at week 24))
- Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Thrombin Peak(Pre-dose (prior to the concizumab administration at week 24))
- Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Free Tissue Factor Pathway Inhibitor (TFPI) Concentration(Pre-dose (prior to the concizumab administration at week 24))
- Haemophila A and Haemophilia B Participants Without Inhibitors: Maximum Concizumab Plasma Concentration (Cmax)(Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h)
- Haemophila A and Haemophilia B Participants Without Inhibitors: Area Under the Concizumab Plasma Concentration-time Curve (AUC)(Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h)
- Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Thromboembolic Events(On demand (arm 1): from week 0 until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off)
- Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Hypersensitivity Type Reactions(On demand (arm 1): from week 0 until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off)
- Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Injection Site Reactions(On demand (arm 1 main part): from randomisation (week 0) until start of concizumab treatment (week 24). Concizumab (arms 2-4): From week 0 up until the 56 week cut-off. Concizumab (arm 1 extension part): From week 25 up until the 56 week cut-off)
- Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Participants With Antibodies to Concizumab(Concizumab (arms 2-4): From start of concizumab treatment (week 0) up until the 56 week cut-off. Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the 56 week cut-off)