Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia Without Inhibitors (explorer8)

Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Haemophilia A Without Inhibitors; Haemophilia B Without Inhibitors
• Intervention / Treatment: Drug: Concizumab

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Algeria
  • Algiers, Algeria, 16000
    • Haematology and Blood Bank Department
  • Constantine, Algeria, 25000
    • CHU Constantine BEN BADIS/ Hematology department
• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
    • Parkville, Victoria, Australia, 3052
      • The Royal Children's Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital - Haemophilia and Haemostasis Centre
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Center of Republic Srpska (205)
• Bulgaria
  • Sofia, Bulgaria, 1527
    • UMHAT Tsaritsa Yoanna - ISUL EAD, Pediatric clinical hematology and oncology
  • Varna, Bulgaria, 9010
    • UMHAT Sveta Marina EAD, Clinic of Pediatric Clinical Hematology and Oncology
• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Eastern Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamltn Hth Sci/McMstr Child Hosp
• Croatia
  • Zagreb, Croatia, 10 000
    • KBC Zagreb_Hematology
• Denmark
  • Copenhagen, Denmark, 2100
    • Copenhagen Center for Heamatology
• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre Foundation
• France
  • Brest, France, 29200
    • Centre Hospitalier Regional Et Universitaire de Brest-Hopital de La Cavale Blanche
  • Caen, France, 14033
    • CHU de Caen - Côte de Nacre
  • Le Kremlin-Bicêtre, France, 94270
    • Hopital de Bicetre
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu
  • Rennes, France, 35033
    • Hôpital Pontchaillou
  • Saint-Priest-en-Jarez, France, 42270
    • Centre Hospitalier Universitaire de Saint Etienne-Hopital Nord
• Germany
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn - Institut für Experimentelle Hämatologie
  • Homburg, Germany, 66424
    • Universität des Saarlandes - Hämostaseologie und Transfusionsmedizin
• Hungary
  • Budapest, Hungary, H-1134
    • MH Eü. Központ -Orszagos Haemophilia Kozpont
• India
  • Karnataka
    • Bangalore, Karnataka, India, 560034
      • St. John's Medical college and Hospital
  • Maharashtra
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital
    • Pune, Maharashtra, India, 411004
      • Sahyadri Speciality Hospital
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • J K Lon Hospital
  • Tamil Nadu
    • Ranipet, Tamil Nadu, India, 632517
      • CMCV
• Israel
  • Tel Litwinsky, Israel, 52621
    • Sheba MC The Israeli National Hemophilia Center
• Italy
  • Roma, Italy, 00161
    • Policlinico Umberto I Sezione Ematologia
  • Torino, Italy, 10126
    • A.O.U Città Salute Scienza Torino
  • FI
    • Florence, FI, Italy, 50134
      • Dipartimento di Ematologia Univ. Firenze
  • MI
    • Milan, MI, Italy, 20124
      • Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano
• Japan
  • Aichi, Japan, 466-8560
    • Nagoya University Hospital_Blood Transfusion
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital, Hematology
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital_Hematology
  • Hyōgo, Japan, 654-0047
    • Hyogo Prefectural Kobe Children's Hospital
  • Hyōgo, Japan, 654-0047
    • Hyogo prefectural kobe children's hospital Dept. of Haem and Onclogy
  • Niigata, Japan, 941-8502
    • Itoigawa sogo Hospital_Department of Pediatrics
  • Osaka, Japan, 546-0006
    • Osaka National Hospital_Dept. of Infectious diseases
  • Saitama, Japan, 330-8777
    • Saitama Children's Med Centre_Hematology-Oncology
  • Saitama, Japan, 350-0495
    • Saitama Medical Univ. Hospital
  • Saitama, Japan, 350-0495
    • Saitama Medical Univ. Hospital_Dep of Int Med, Cent for Hemo
  • Shizuoka, Japan, 420-8660
    • Shizuoka Children's Hospital
  • Shizuoka, Japan, 420-8660
    • Shizuoka Children's Hospital, Hematology-Oncology
  • Tokyo, Japan, 167-0035
    • Ogikubo Hospital_Pediatries & Blood
  • Tokyo, Japan, 157-8535
    • National Center for Child Health and Development_Hematology
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Vilnius University Hospital Santaros Klinikos
  • Vilnius, Lithuania, 08406
    • Children Oncohaematology department Children's Hospital,
• Malaysia
  • Ampang, Selangor, Malaysia, 68000
    • Hospital Ampang
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Hospital Ampang
• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez
• Poland
  • Lublin, Poland, 20-081
    • Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku
  • Lublin, Poland, 20-093
    • Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa
  • Wroclaw, Poland, 50-367
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
  • Greater Poland Voivodeship
    • Poznan, Greater Poland Voivodeship, Poland, 60-569
      • Uniwersytecki Szpital Kliniczny w Poznaniu
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 30-688
      • Szpital Uniwersytecki, Oddzial Kliniczny Hematologii
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 02-776
      • Instytut Hematologii I Transfuzjologii
• Portugal
  • Porto, Portugal, 4200-319
    • ULS São João, E.P.E.
• Russia
  • Krasnodar, Russia, 350007
    • Children Regional Clinical Hospital
  • Moscow, Russia, 119049
    • Morozovskaya municipal children hospital
  • Moscow, Russia, 125167
    • National Medical Research institution of haemotology
  • Petrozavodsk, Russia, 185019
    • Republican Hospital n.a. V. A. Baranov
  • Saint Petersburg, Russia, 191186
    • City out-patient clinic 37, City Hemophilia Centre
• Serbia
  • Belgrade, Serbia, 11070
    • Institute for Mother and Child Health Care of Serbia
  • Belgrade, Serbia, 11000
    • Clinical Centre of Serbia, Institute for Haematology
  • Kragujevac, Serbia, 34000
    • University Clinical Centre Kragujevac
  • Novi Sad, Serbia, 21000
    • Clinical Centre of Vojvodina
• Slovakia
  • Bratislava, Slovakia, 851 07
    • Nemocnica sv. Cyrila a Metoda, UNB,Klinika hemat. a transfuz
• South Africa
  • Gauteng
    • Parktown, Johannesburg, Gauteng, South Africa, 2193
      • Charlotte Maxeke Johannesburg Academic Hospital
  • Limpopo
    • Polokwane, Limpopo, South Africa, 0699
      • Pietersburg Hospital
• South Korea
  • Daejeon, South Korea, 35233
    • Daejeon Eulji Medical Center, Eulji University
  • Daejeon, South Korea, 35233
    • Daejeon Eulji University Hospital
  • Jeju City, South Korea, 63241
    • Jeju National University Hospital
  • Jeju-do, South Korea, 63241
    • Jeju National University Hospital
  • Seoul, South Korea, 03722
    • Severance Hospital, Yonsei University Health System
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Oviedo, Spain, 33011
    • Hospital Univ. Central de Asturias
  • Seville, Spain, 41013
    • Hospital Virgen Del Rocio
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
• Sweden
  • Malmo, Sweden, 214 28
    • Koagulationsmottagning - SUS
  • Solna, Sweden, 171 64
    • Koagulationsmottagningen
• Switzerland
  • Zurich, Switzerland, 8091
    • Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital_Department of Haematology
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Acıbadem Adana Hastanesi-Hematoloji
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe University Medical Faculty
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Üniversitesi Hastanesi- Endokrinoloji
  • Edirne, Turkey (Türkiye), 22030
    • Trakya Üniversitesi Tıp Fakültesi Hastanesi-Hematoloji
  • Izmir, Turkey (Türkiye), 35100
    • Ege Üniversitesi Hastanesi- Hematoloji
  • Samsun, Turkey (Türkiye), 55139
    • Ondokuz Mayıs Üniversitesi Hastanesi - Hematoloji
  • Beşevler/Ankara
    • Ankara, Beşevler/Ankara, Turkey (Türkiye), 06500
      • Gazi University
    • Ankara, Beşevler/Ankara, Turkey (Türkiye), 06500
      • Gazi Üniversitesi Hastanesi- Hematoloji
  • Capa-ISTANBUL
    • Capa-ISTANBUL, Capa-ISTANBUL, Turkey (Türkiye), 34093
      • İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Onkoloji Enstitüsü
• Ukraine
  • Kyiv, Ukraine, 01135
    • National specialized children's hospital 'OHMATDYT' - Haemostasis centre
  • Lviv, Ukraine, 79044
    • Institute of blood pathology and transfusion medicine of NAMSU - General and haematol. surgery
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital
  • London, United Kingdom, NW3 2QG
    • Royal Free Haemophilia Comprehensive Care Center
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital - Haemophilia
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles - Endocrinology
    • Orange, California, United States, 92868
      • Center for Inherited Blood Disorders
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Center for Blood Disorders Augusta University
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hemophilia-Thromb Ctr
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa_Iowa City
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
    • Lansing, Michigan, United States, 48911
      • Michigan State University
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novant Hlth Vasc Ins Charlotte
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • M.S. Hershey Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center_Nashville_0
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas San Antonio
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Versiti, CCBD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2: Concizumab prophylaxis; HA and HB patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.	Drug: Concizumab; 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.
Experimental: 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.	Drug: Concizumab; 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.
Experimental: 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.	Drug: Concizumab; 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.
Experimental: 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.	Drug: Concizumab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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		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.	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		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.	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		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		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		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.	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.	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.	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.	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.	Pre-dose, Week 24: 3 hours (h), 6h, 9h, 24h

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• Angchaisuksiri P, von Mackensen S, Apte S, Benson G, Eichler H, Findley A, Matsushita T, Mazini Tavares CM, Puggaard Ravn M, Sathar J, Villarreal Martinez L, Young G. Concizumab prophylaxis in people with hemophilia A or B without inhibitors: patient-reported outcome results from the phase 3 explorer8 study. Res Pract Thromb Haemost. 2025 Feb 20;9(2):102705. doi: 10.1016/j.rpth.2025.102705. eCollection 2025 Feb.
• Chowdary P, Angchaisuksiri P, Apte S, Astermark J, Benson G, Chan AKC, Jimenez Yuste V, Matsushita T, Hogh Nielsen AR, Sathar J, Sutton C, Saulyte Trakymiene S, Tran H, Villarreal Martinez L, Wheeler AP, Windyga J, Young G, Thaung Zaw JJ, Eichler H. Concizumab prophylaxis in people with haemophilia A or haemophilia B without inhibitors (explorer8): a prospective, multicentre, open-label, randomised, phase 3a trial. Lancet Haematol. 2024 Dec;11(12):e891-e904. doi: 10.1016/S2352-3026(24)00307-7. Epub 2024 Nov 6.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2019
• Primary Completion (Actual): July 12, 2022
• Study Completion (Estimated): February 21, 2028

Study Registration Dates

• First Submitted: September 5, 2019
• First Submitted That Met QC Criteria: September 5, 2019
• First Posted (Actual): September 9, 2019

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemophilia A; Hemophilia B; concizumab
• Other Study ID Numbers: NN7415-4307; U1111-1225-9722 (Other Identifier: World Health Organization (WHO)); 2018-004891-36 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No