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Active, Not Recruiting

NCT Number: NCT04082429

Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia Without Inhibitors

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Haemophilia A Without Inhibitors Haemophilia B Without Inhibitors

Age range

12 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 3

Primary location

Haematology and Blood Bank Department, Algiers, Algeria

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.)

Treatment and study plan

Concizumab

Drug

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.

Primary outcomes

  1. 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.

  2. 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

  1. Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes

    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

    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.

  2. Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes

    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

    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.

  3. Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes

    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

    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.

  4. Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes

    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

    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.

  5. Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes

    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

    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.

  6. Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes

    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

    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.

  7. Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Target Joint Bleeding Episodes

    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

    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.

  8. Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Target Joint Bleeding Episodes

    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

    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.

  9. Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Thromboembolic Events

    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

    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.

  10. 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)

  11. Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Hypersensitivity Type Reactions

    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

    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.

  12. 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)

  13. Haemophila A and Haemophilia B Participants Without Inhibitors: Number of Injection Site Reactions

    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

    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.

  14. 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)

  15. 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

  16. 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)

  17. Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose (Trough) Concizumab Plasma Concentration (Ctrough)

    Time frame: Pre-dose (prior to the concizumab administration at week 24)

    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.

  18. Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Thrombin Peak

    Time frame: Pre-dose (prior to the concizumab administration at week 24)

    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.

  19. Haemophila A and Haemophilia B Participants Without Inhibitors: Pre-dose Free Tissue Factor Pathway Inhibitor (TFPI) Concentration

    Time frame: Pre-dose (prior to the concizumab administration at week 24)

    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.

  20. Haemophila A and Haemophilia B Participants Without Inhibitors: Maximum Concizumab Plasma Concentration (Cmax)

    Time frame: Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h

    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.

  21. Haemophila A and Haemophilia B Participants Without Inhibitors: Area Under the Concizumab Plasma Concentration-time Curve (AUC)

    Time frame: Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h

    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.

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B Without Inhibitors

Acronym: explorer8

Important dates

Study start
2019
Primary completion
2022
Study completion
2028
First posted
Sep 9, 2019
Registry last updated
Jun 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.