Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Concizumab · 6 trials · 8 indications
Count of episode(s)
Count of episode(s)
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Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.
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Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.
Rate of treated spontaneous and traumatic bleeding episodes is presented. The observation period used for reporting this endpoint is on-treatment without ancillary therapy excl. data on initial regimen for participants exposed to both regimens (OTwoATexIR). It is defined as the time period where participants are treated by either the new concizumab dosing regimen or the initial concizumab dosing regimen (only included if not exposed to the new concizumab dosing regimen) or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleed during any of the cases. The data is reported in the terms of annualised bleeding rate (ABR). Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.
The number of bleeding episodes that were treated during at least 24 weeks from treatment onset are presented. The data is presented while on last dose level when the bleed occurred.
The number of bleeding episodes that were treated during at least 24 weeks from treatment onset (week 0) are presented.
| Arm | Type | Description |
|---|---|---|
| Concizumab-naïve patients | EXPERIMENTAL | Concizumab-naïve participants below 12 years of age at the time of consent/assent |
| Patients coming from compassionate use | EXPERIMENTAL | Patients previously treated with concizumab via compassionate use, either on an individual patient basis or through the concizumab compassionate use programme NN7415-4807 |
| Arm 1: No prophylaxis (PPX) | EXPERIMENTAL | 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 2: Concizumab prophylaxis | EXPERIMENTAL | HA and HB patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. |
| Arm 3: Concizumab prophylaxis | EXPERIMENTAL | The HA patients enrolled into the concizumab phase 2 trial NN7415-4255 (explorer 5) will be offered enrolment into this arm. |
| Arm 4: Concizumab prophylaxis | EXPERIMENTAL | 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. |
| Arm 1: No prophylaxis | EXPERIMENTAL | Haemophilia A with inhibitors (HAwI) and haemophilia B with inhibitors (HBwI) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. In the extension part, patients in arm 1 will receive daily concizumab subcutaneous (s.c., under the skin) injections. |
| Concizumab | EXPERIMENTAL | Daily administration of concizumab to both on-demand and prophylaxis patients |
| Eptacog alfa and concizumab | ACTIVE_COMPARATOR | Eptacog alfa administered on-demand during bleeding episodes as the only intervention during the main phase. Concizumab given in the extension phase |
| Placebo | PLACEBO_COMPARATOR | - |
| Name | Type | Description |
|---|---|---|
| Concizumab | DRUG | 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. |
| Turoctocog alfa | DRUG | Breakthrough bleeding episodes will be treated by the patients at home with turoctocog alfa at the discretion of the study doctor, who will also choose dose levels |
| Eptacog alfa | DRUG | A single dose of 90 μg/kg eptacog alfa one week after dosing with concizumab. On-demand treatment during bleeding episodes in both treatment arms |
| placebo | DRUG | Administered subcutaneously (s.c., under the skin) |
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...
Concizumab is an investigational medicine being developed for congenital bleeding disorders, specifically haemophilia A and haemophilia B, including patients with and without inhibitors. It is also being studied in haemostasis. It is designed as a prophylactic treatment to reduce bleeding episodes in people with these inherited clotting disorders.
Concizumab targets tissue factor pathway inhibitor, or TFPI. It is a monoclonal antibody that inhibits TFPI. By blocking TFPI, concizumab is intended to enhance thrombin generation and promote clot formation in patients with haemophilia, a mechanism that works independently of factor VIII or factor IX replacement.
Concizumab is being developed by Novo Nordisk A/S, which trades under the ticker NVO. Novo Nordisk is the sponsor of the clinical trial program evaluating concizumab in haemophilia A and B with and without inhibitors.
Concizumab is in Phase 2 development according to its overall program status, but it is also being evaluated in Phase 3 clinical trials. It is an investigational drug and has not been approved by the FDA. The Phase 3 studies are currently active and not recruiting.
Concizumab has been studied in several clinical trials, including NCT05135559, a Phase 3 study in haemophilia A and B with or without inhibitors; NCT04083781, a Phase 3 study in haemophilia with inhibitors; NCT04082429, a Phase 3 study in haemophilia without inhibitors; and NCT03196297, a completed Phase 2 trial in severe haemophilia A without inhibitors.