A Research Study on How Well Concizumab Works for You if You Have Haemophilia A or B With or Without Inhibitors (Explorer10)

Open-label Study Investigating Efficacy, Safety and Pharmacokinetics of Concizumab Prophylaxis in Children Below 12 Years With Haemophilia A or B With or Without Inhibitors

This study will test how well a new medicine called concizumab works for participants who have haemophilia A or B with or without inhibitors. The purpose is to show that concizumab can prevent bleeds and is safe to use.

Participants will have to inject the study medicine every day under the skin with a pen-injector.

The study will last for at least 2 years and up to about 4 years. The length of time the participant will be in the study depends on if the study medicine will be available for purchase in their country.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 153
• 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
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Center of Republic Srpska (545)
  • Tuzla, Bosnia and Herzegovina, 75000
    • University Clinical Centre Tuzla
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sveti Georgi EAD, Plovdiv, Clinic of Pediatrics
  • Sofia, Bulgaria, 1527
    • UMHAT Tsaritsa Yoanna - ISUL EAD, Pediatric clinical hematology and oncology
  • Varna, Bulgaria, 9010
    • UMHAT "Sveta Marina" EAD
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • BC Children's Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital
• Estonia
  • Tallinn, Estonia, 13419
    • Tallinn Children's Hospital
• France
  • Chambéry, France, 73000
    • Centre Hospitalier Metropole Savoie
  • Le Kremlin-Bicêtre, France, 94275
    • Ap-Hp-Hopital de Bicetre-1
  • Paris, France, 75015
    • AP-HP-HOPITAL NECKER_Service d'hématologie
• Greece
  • Athens, Greece, GR-11527
    • Aghia Sophia Childrens' Hospital
  • Thessaloniki, Greece, GR 54642
    • 'Ippokrateio' General Hospital of Thessaloniki
  • Thessaloniki, Greece, 54642
    • 'Ippokrateio' General Hospital of Thessaloniki
• India
  • Assam
    • Guwahati, Assam, India, 781032
      • Guwahati Medical College
  • Gujarat
    • Surat, Gujarat, India, 395002
      • Nirmal Hospital Pvt. Ltd.
  • Maharashtra
    • Kolhāpur, Maharashtra, India, 416005
      • SSSH_Dept. of Clinical Haematology & Haemato Oncology
    • Mumbai, Maharashtra, India, 400012
      • Seth GS Medical College & KEM Hospital
    • Mumbai, Maharashtra, India, 400022
      • K.J Somaiya Hospital and Research Centre
    • Mumbai, Maharashtra, India, 400066
      • MCGM - Comprehensive Thalassemia Care
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital
  • Odisha
    • Cuttack, Odisha, India, 753007
      • S.C.B. Medical College
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • J K Lon Hospital
  • Uttar Pradesh
    • Noida, Uttar Pradesh, India, 201303
      • Post Graduate Institute of Child Health
  • Uttart Pradesh
    • Lucknow, Uttart Pradesh, India, 226014
      • SGPGI
• Italy
  • Catania, Italy, 95123
    • A.O.U policlinico "G. Rodolico-San Marco"
  • Florence, Italy, 50134
    • Dipartimento di Ematologia Univ. Firenze
  • Padua, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Parma, Italy, 43126
    • Azienda Ospedaliera-Universitaria Parma
• Japan
  • Kanagawa, Japan, 216-8511
    • St. Marianna University School of Medicine Hospital_Pediatrics
  • Saitama, Japan, 330-8777
    • Saitama Children's Med Centre_Hematology-Oncology
• Lebanon
  • Beirut, Lebanon, 961
    • Saint George Hospital University Medical Center
  • Tripoli, Lebanon, 1434
    • Hospital Nini
• Lithuania
  • Vilnius, Lithuania, LT-08406
    • Centre of Oncology and Hematology, Vilnius University
• Malaysia
  • Kuala Lumpur
    • Kampung Baru, Kuala Lumpur, Malaysia, 50300
      • Hospital Tunku Azizah
  • Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10450
      • Hospital Pulau Pinang
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital
  • Terengganu
    • Kuala Terengganu, Terengganu, Malaysia, 20400
      • Hospital Sultanah Nur Zahirah
• North Macedonia
  • Skopje, North Macedonia, 1000
    • PHI University Clinic for Children's Diseases Skopje
• Norway
  • Oslo, Norway, 0372
    • Klinisk forskningspost
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Lublin, Poland, 20-093
    • Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa
  • Warsaw, Poland, 02-091
    • Uniwersyteckie Centrum Kliniczne WUM
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego
• Romania
  • Bucharest, Romania, 022328
    • Clinic of Haematology, Fundeni Clinical Institute
  • Cluj-Napoca, Romania, 400177
    • Spitalul Clinic de Urgenta pentru Copii Cluj Napoca
  • Oradea, Romania, 410469
    • Spitalul Clinic Judetean De Urgenta Bihor
• South Africa
  • Gauteng
    • Parktown, Johannesburg, Gauteng, South Africa, 2193
      • Charlotte Maxeke Johannesburg Academic Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Málaga, Spain, 29009
    • Hospital Regional Universitario de Malaga
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Virgen de la Arrixaca - Hematología
• Sweden
  • Gothenburg, Sweden, 413 46
    • Koagulationscentrum
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital_Bangkok_0
  • Bangkok, Thailand, 10700
    • Siriraj Hospital - Hematology and Oncology
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital_Pediatric Hematology-Oncology
  • Mueang Distirct,
    • Ubon Ratchathani, Mueang Distirct,, Thailand, 34000
      • Sunpasitthiprasong Hospital_Pediatrics Department
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01130
    • Acibadem Adana Hastanesi
  • Adana, Turkey (Türkiye), 01130
    • Acıbadem Adana Hastanesi-Hematoloji
  • Izmir, Turkey (Türkiye), 35100
    • Ege Universitesi Tip Fakultesi
  • Izmir, Turkey (Türkiye), 35100
    • Ege Üniversitesi Hastanesi- Hematoloji
  • Samsun, Turkey (Türkiye), 55139
    • Ondokuz Mayis University Medical Faculty Ped. Haematology
  • 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
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • Bristol, United Kingdom, BS2 8BJ
    • University Hospitals Bristol & Weston NHS Foundation Trust
  • London, United Kingdom, WC1N 3HR
    • Great Ormond Street Hospital for Children
  • London, United Kingdom, SE1 7EH
    • Evelina London Children's Hospital - Haemophilia
• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Childrens Hosp San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Florida
    • Orlando, Florida, United States, 32806
      • Arnold Palmer Children's Hospital
    • Orlando, Florida, United States, 32827
      • Nemours Child Orlando Hem/Onc.
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta Univ/Childrens Hosp-GA
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Childrens Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Indiana Hemophilia-Thromb Ctr
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
    • New Orleans, Louisiana, United States, 70118
      • Children's Hosp-New Orleans
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • The Children's Mercy Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Children's Nebraska
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • ECU Sickle Cell Comp Clinic
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • St Christopher Hosp for Child
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt Hemostasis Treatment Clinic
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Hospital-Hematology-Oncology
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital_Houston
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Pediatrics Hematology/Oncology Clinic Battle Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 1%) or moderate/severe congenital haemophilia B (FIX (coagulation factor IX) below or equal to 2%), or congenital haemophilia with inhibitors.
• For arm 1 only: Male aged below 12 years of age at the time of signing informed consent.

• For arm 1 only: Patients with inhibitors (haemophilia A with inhibitors or haemophilia B with inhibitors)

  1. Patients with HAwI (haemophilia A with inhibitors) with historical medical records of a total of at least 26 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia <1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available).
  2. Patients with HBwI (haemophilia B with inhibitors) with historical medical records of a total of at least 26 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia <1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available).
  3. Patients with HBwI regardless of the regimen and duration of previous haemophilia treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products)

• For arm 1 only: Patients without inhibitors (haemophilia A or haemophilia B)

  1. Patients with historical medical records of at least 52 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products; Surgery related PPX or short-term PPX (e.g., in relation to a severe bleed) is not allowed) during the last year prior to enrolment and with at least 3 documented treated bleeds (For participants less than (<) 2 years of age there is no limitation for number of documented treated bleeds in the medical history) during this period
  2. Patients with historical medical records of a total of at least 26 weeks of PPX (prophylaxis) treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia <1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available)
• For arm 2 only: Male patients (regardless of age) previously treated with concizumab via compassionate use.

Exclusion Criteria:

• Known or suspected hypersensitivity to study intervention or related products.
• Known inherited or acquired coagulation disorder other than congenital haemophilia.
• Ongoing or planned Immune Tolerance Induction treatment.
• History of thromboembolic disease (aIncludes 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: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concizumab-naïve patients; Concizumab-naïve participants below 12 years of age at the time of consent/assent	Drug: Concizumab; 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.
Experimental: Patients coming from compassionate use; Patients previously treated with concizumab via compassionate use, either on an individual patient basis or through the concizumab compassionate use programme NN7415-4807	Drug: Concizumab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients treated on demand during at least the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic)	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated joint bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target joints	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients treated on-demand during at least the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic)	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients treated on-demand during at least the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients treated on-demand at least the last 52 weeks prior enrolment: Number of treated joint bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients treated on-demand at least the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target joints	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic)	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated joint bleeding episodes	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target joints	Count of episode(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
Concizumab-naïve pateints - Number of treatment emergent adverse events, reported both separately for inhibitor and non-inhibitor patients and combined	Count of event(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
Number of thromboembolic events, reported both separately for inhibitor and non-inhibitor patients and combined	Count of event(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
Number of hypersensitivity type reactions, reported both separately for inhibitor and non-inhibitor patients and combined	Count of event(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
Number of injection site reactions, reported both separately for inhibitor and non-inhibitor patients and combined	Count of event(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
Number of patients who develop antibodies to concizumab - yes/no, reported both separately for inhibitor and non-inhibitor patients and combined	Count of patient(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
Number of treatment emergent adverse events, reported both separately for inhibitor and non-inhibitor patients and combined	Count of event(s)	From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
Concizumab plasma concentrations prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined	Measured in ng/mL	Week 32
Peak thrombin generation prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined	Measured in nM	Week 32
Free TFPI concentration prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined	Measured in ng/mL	Week 32
Pre-dose (trough) concizumab plasma concentration (Ctrough), reported both separately for inhibitor and non-inhibitor patients and combined	Measured in ng/mL	Prior to the concizumab administration at week 20
Maximum concizumab plasma concentration (Cmax), reported both separately for inhibitor and non-inhibitor patients and combined	Measured in ng/mL	From 0 to 24 hours where 0 is the time of the concizumab dose at week 20
Area under the concizumab plasma concentration-time curve (AUC), reported both separately for inhibitor and non-inhibitor patients and combined	Measured in ng*hr/mL	From 0 to 24 hours where 0 is the time of the concizumab dose at week 20

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2022
• Primary Completion (Estimated): April 21, 2026
• Study Completion (Estimated): November 2, 2029

Study Registration Dates

• First Submitted: November 15, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 26, 2021

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 29, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A; concizumab
• Other Study ID Numbers: NN7415-4616; U1111-1247-7330 (Other Identifier: World Health Organization (WHO)); 2020-000504-11 (EudraCT Number); jRCT2031220097 (Registry Identifier: JAPIC)

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