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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
156
When patients are randomised/allocated to concizumab prophylaxis, they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week (Wk) 0) (arm 2, 3 and 4) or visit 9a (Wk 24) (arm 1) followed by an initial daily dose of 0.20 mg/kg concizumab from treatment day 2. Within an initial 5-8-week dose adjustment period on 0.20 mg/kg concizumab, the patients can be increased or decreased in dose to 0.25 mg/kg or 0.15 mg/kg concizumab. A potential dose adjustment will take place at visit 4a.1 (Wk 6) or 9a.3 (Wk 30) and will be based on the concizumab exposure level measured at the previous visit 4a (Wk 6) or 9a.2 (Wk 28). Patients who have concizumab exposure levels of 200-4000 ng/mL will stay at 0.20 mg/kg concizumab. Patients in arm 1 will continue on-demand treatment with their usual replacement therapy until visit 9a (week 24; end of main part). In the extension part, patients in arm 1 will receive daily concizumab subcutaneous injections.
Children's Hospital Los Angeles - Endocrinology
Los Angeles, California, United States
Center for Inherited Blood Disorders
Orange, California, United States
Center for Blood Disorders Augusta University
Augusta, Georgia, United States
Indiana Hemophilia-Thromb Ctr
Indianapolis, Indiana, United States
University of Iowa_Iowa City
Iowa City, Iowa, United States
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
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.
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
Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
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.
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
Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia A participants without inhibitors in arm 4 participants who had been on stable PPX at least 24 weeks in study 4322 is presented. The observation period used for reporting this endpoint is on stable treatment without ancillary therapy excluding data before restart (OT stable woATexBR). It is defined as the time period where participants are on stable PPX in study NN7415-4322 combined with the time period after the treatment pause in NN7415-4307 where the same participants are on the maintenance dose and have not used factor-containing products not related to treatment of a bleed. The data is reported in the terms of ABR.
Time frame: 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
Rate of treated spontaneous and traumatic bleeding episodes for haemophilia B participants without inhibitors in arm 4 participants who had been on stable PPX at least 24 weeks in study 4322 is presented. The observation period used for reporting this endpoint is OT stable woATexBR. It is defined as the time period where participants are on stable PPX in study NN7415-4322 combined with the time period after the treatment pause in NN7415-4307 where the same participants are on the maintenance dose and have not used factor-containing products not related to treatment of a bleed. The data is reported in the terms of ABR.
Time frame: 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
Rate of treated spontaneous bleeding episodes for haemophilia A 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.
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Children's Hospital of Michigan
Detroit, Michigan, United States
Michigan State University
Lansing, Michigan, United States
Novant Hlth Vasc Ins Charlotte
Charlotte, North Carolina, United States
M.S. Hershey Medical Center
Hershey, Pennsylvania, United States
Vanderbilt University Medical Center_Nashville_0
Nashville, Tennessee, United States
...and 98 more locations
Time frame: 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
Rate of treated spontaneous 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.
Time frame: 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
Rate of treated spontaneous and traumatic joint bleeding episodes for haemophilia A 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.
Time frame: 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
Rate of treated spontaneous and traumatic joint 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.
Time frame: 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
Rate of treated spontaneous and traumatic target joint bleeding episodes for haemophilia A 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.
Time frame: 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
Rate of treated spontaneous and traumatic target joint 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.
Time frame: 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
Number of thromboembolic events in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment (OT). It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. 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.
Time frame: 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 Thromboembolic Events
Time frame: From week 0 to end of trial (up to 384 weeks)
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Hypersensitivity Type Reactions
Number of hypersensitivity type reactions in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OT. It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. 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.
Time frame: 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
Time frame: From week 0 to end of trial (up until 384 weeks)
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Injection Site Reactions
Number of injection site reactions in haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OT. It is defined as the time period where participants were considered to be affected by no PPX (on-demand treatment) or concizumab PPX. 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.
Time frame: 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 Injection Site Reactions
Time frame: 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
Time frame: 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
Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Participants With Antibodies to Concizumab
Time frame: 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)
Ctrough for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment without data before re-start (OTexBR). It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Time frame: Pre-dose (prior to the concizumab administration at week 24)
Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Thrombin Peak
Pre-dose thrombin peak for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Time frame: 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 free TFPI for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Time frame: Pre-dose (prior to the concizumab administration at week 24)
Haemophila A and Haemophilia B Participants Without Inhibitors: Maximum Concizumab Plasma Concentration (Cmax)
Cmax for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Time frame: 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)
AUC for haemophilia A and haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTexBR. It is defined as the time period after restart where participants were considered to be affected by no PPX (on-demand treatment) or treatment with the new concizumab regimen.
Time frame: Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h