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

NCT ID: NCT04082429

Last Updated: 2025-12-05

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-13
• Study Completion Date: 2028-02-21

Brief Summary

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.

Conditions

Haemophilia A Without Inhibitors; Haemophilia B Without Inhibitors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Concizumab

Intervention Type: 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.

Arm 2: Concizumab prophylaxis

HA and HB patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.

Group Type: EXPERIMENTAL

Concizumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Concizumab

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

Concizumab

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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.)

• Minimum Eligible Age: 12 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Reporting Anchor and Disclosure (1452)

Role: STUDY_DIRECTOR

Novo Nordisk A/S

Locations

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

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

University of Texas San Antonio

San Antonio, Texas, United States

Versiti, CCBD

Milwaukee, Wisconsin, United States

Haematology and Blood Bank Department

Algiers, , Algeria

CHU Constantine BEN BADIS/ Hematology department

Constantine, , Algeria

The Alfred

Melbourne, Victoria, Australia

Royal Children's Hospital

Parkville, Victoria, Australia

Fiona Stanley Hospital - Haemophilia and Haemostasis Centre

Murdoch, Western Australia, Australia

University Clinical Center of Republic Srpska (205)

Banja Luka, , Bosnia and Herzegovina

UMHAT Tsaritsa Yoanna-ISUL EAD

Sofia, , Bulgaria

UMHAT "Sveta Marina" EAD Clinic of Pediatric Clinical Hemat

Varna, , Bulgaria

Eastern Health Authority

St. John's, Newfoundland and Labrador, Canada

Hamltn Hth Sci/McMstr Child Hosp

Hamilton, Ontario, Canada

KBC Zagreb, Rebro, Hemofilija centar

Zagreb, , Croatia

Copenhagen Center for Heamatology

Copenhagen, , Denmark

North Estonia Medical Centre Foundation

Tallinn, , Estonia

Centre Hospitalier Regional Et Universitaire de Brest-Hopital de La Cavale Blanche

Brest, , France

CHU de Caen - Côte de Nacre

Caen, , France

Hopital de Bicetre

Le Kremlin-Bicêtre, , France

Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu

Nantes, , France

Hôpital Pontchaillou

Rennes, , France

Centre Hospitalier Universitaire de Saint Etienne-Hopital Nord

Saint-Priest-en-Jarez, , France

Universitätsklinikum Bonn - Institut für Experimentelle Hämatologie

Bonn, , Germany

Universitätsklinikum des Saarlandes - Hämostaseologie und Transfusionsmedizin

Homburg, , Germany

MH Eü. Központ -Orszagos Haemophilia Kozpont

Budapest, , Hungary

St. John's Medical college and Hospital

Bangalore, Karnataka, India

Sahyadri Speciality Hospital

Pune, Maharashtra, India

Sahyadri Super Speciality Hospital

Pune, Maharashtra, India

J K Lon Hospital

Jaipur, Rajasthan, India

CMCV

Ranipet, Tamil Nadu, India

Sheba MC The Israeli National Hemophilia Center

Tel Litwinsky, , Israel

Dipartimento di Ematologia Univ. Firenze

Florence, FI, Italy

Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano

Milan, MI, Italy

Policlinico Umberto I Sezione Ematologia

Roma, , Italy

A.O.U Città Salute Scienza Torino

Torino, , Italy

Nagoya University Hospital_Blood Transfusion

Aichi, , Japan

Hiroshima University Hospital, Hematology

Hiroshima, , Japan

Hyogo prefectural kobe children's hospital

Hyōgo, , Japan

Itoigawa sogo Hospital_Department of Pediatrics

Niigata, , Japan

Osaka National Hospital

Osaka, , Japan

Saitama Children's Med Centre_Hematology-Oncology

Saitama, , Japan

Saitama Medical Univ. Hospital

Saitama, , Japan

Shizuoka Children's Hospital, Hematology-Oncology

Shizuoka, , Japan

Shizuoka Children's Hospital

Shizuoka, , Japan

National Center for Child Health and Development_Hematology

Tokyo, , Japan

Ogikubo Hospital_Pediatries & Blood

Tokyo, , Japan

Children Oncohaematology department Children's Hospital,

Vilnius, , Lithuania

Vilnius University hospital Santaros klinikos

Vilnius, , Lithuania

Hospital Ampang

Ampang, Selangor, Malaysia

Hospital Ampang

Ampang, Selangor, , Malaysia

Hospital Universitario Dr. José Eleuterio González

Monterrey, Nuevo León, Mexico

Uniwersytecki Szpital Kliniczny W Poznaniu

Poznan, Greater Poland Voivodeship, Poland

Szpital Uniwersytecki, Oddzial Kliniczny Hematologii

Krakow, Lesser Poland Voivodeship, Poland

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, Poland

Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku

Lublin, , Poland

Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa

Lublin, , Poland

Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu

Wroclaw, , Poland

ULS São João, E.P.E.

Porto, , Portugal

Children Regional Clinical Hospital

Krasnodar, , Russia

Morozovskaya municipal children hospital

Moscow, , Russia

National Medical Research institution of haemotology

Moscow, , Russia

Republican Hospital n.a. V. A. Baranov

Petrozavodsk, , Russia

City out-patient clinic 37, City Hemophilia Centre

Saint Petersburg, , Russia

Clinical Centre of Serbia, Institute for Haematology

Belgrade, , Serbia

Institute for Mother and Child Health Care of Serbia

Belgrade, , Serbia

University Clinical Centre Kragujevac

Kragujevac, , Serbia

Clinical Centre of Vojvodina

Novi Sad, , Serbia

Nemocnica sv. Cyrila a Metoda, UNB,Klinika hemat. a transfuz

Bratislava, , Slovakia

Charlotte Maxeke Johannesburg Academic Hospital

Parktown, Johannesburg, Gauteng, South Africa

Pietersburg Hospital

Polokwane, Limpopo, South Africa

Daejeon Eulji Medical Center, Eulji University

Daejeon, , South Korea

Daejeon Eulji University Hospital

Daejeon, , South Korea

Jeju National University Hospital

Jeju City, , South Korea

Jeju National University Hospital

Jeju-do, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Hospital Universitario La Paz

Madrid, , Spain

Hospital Regional Universitario de Málaga

Málaga, , Spain

Hospital Univ. Central de Asturias

Oviedo, , Spain

Hospital Virgen del Rocío

Seville, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Koagulationsmottagning

Malmo, , Sweden

Koagulationsmottagningen

Solna, , Sweden

Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie

Zurich, , Switzerland

RAMA -Hemato-Med_Department of Haematology

Bangkok, , Thailand

Gazi University

Ankara, Beşevler/Ankara, Turkey (Türkiye)

Gazi Üniversitesi Hastanesi- Hematoloji

Ankara, Beşevler/Ankara, Turkey (Türkiye)

İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Onkoloji Enstitüsü

Capa-ISTANBUL, Capa-ISTANBUL, Turkey (Türkiye)

Acıbadem Adana Hastanesi-Hematoloji

Adana, , Turkey (Türkiye)

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Hacettepe Üniversitesi Hastanesi- Endokrinoloji

Ankara, , Turkey (Türkiye)

Trakya Üniversitesi Tıp Fakültesi Hastanesi-Hematoloji

Edirne, , Turkey (Türkiye)

Ege Üniversitesi Hastanesi- Hematoloji

Izmir, , Turkey (Türkiye)

Ondokuz Mayis University Medical Faculty Ped. Haematology

Samsun, , Turkey (Türkiye)

National specialized children's hospital 'OHMATDYT' - Haemostasis centre

Kyiv, , Ukraine

Institute of blood pathology and transfusion medicine of NAMSU - General and haematol. surgery

Lviv, , Ukraine

Belfast City Hospital

Belfast, , United Kingdom

Royal Free Haemophilia Comprehensive Care Center

London, , United Kingdom

Royal Free Haemophilia Comprehensive Care Centre

London, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Countries

United States; Algeria; Australia; Bosnia and Herzegovina; Bulgaria; Canada; Croatia; Denmark; Estonia; France; Germany; Hungary; India; Israel; Italy; Japan; Lithuania; Malaysia; Mexico; Poland; Portugal; Russia; Serbia; Slovakia; South Africa; South Korea; Spain; Sweden; Switzerland; Thailand; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40166710 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39521008 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1225-9722

Identifier Type: OTHER

Identifier Source: secondary_id

2018-004891-36

Identifier Type: REGISTRY

Identifier Source: secondary_id

NN7415-4307

Identifier Type: -

Identifier Source: org_study_id