Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia With Inhibitors

NCT ID: NCT04083781

Last Updated: 2026-01-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 134 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-21
• Study Completion Date: 2027-02-21

Brief Summary

This study will test how well a new medicine called concizumab works in the body of people with haemophilia A or B with 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 get 1 injection with the study medicine every day under the skin. This participants will have to do themselves and 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 about seven years. The length of time the participants will be in the study depends on when they agreed to take part or when the medicine is available for purchase in their country (31 December 2026 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. Participants will be asked to record information into an electronic diary during the study and may also be asked to wear an activity tracker.

Conditions

Haemophilia A With Inhibitors; Haemophilia B With Inhibitors

Study Design

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

Study Groups

Arm 1: No prophylaxis

Haemophilia A with inhibitors (HAwI) and haemophilia B with inhibitors (HBwI) patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. In the extension part, patients in arm 1 will receive daily concizumab subcutaneous (s.c., under the skin) injections.

Group Type: EXPERIMENTAL

Concizumab

Intervention Type: DRUG

Concizumab will be administered daily subcutaneously (s.c., under the skin). When patients are randomised to concizumab prophylaxis they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week 0: arm 2, 3 \& 4) or visit 9a (week 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 (week 6: arm 2, 3 \& 4) or 9a.3 (week 30: arm 1) and will be based on the concizumab exposure level measured at the previous visit 4a (week 4) or 9a.2 (week 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 bypassing product until visit 9a (week 24: end of main part for arm 1).

Arm 2: Concizumab prophylaxis

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

Group Type: EXPERIMENTAL

Concizumab

Intervention Type: DRUG

Concizumab will be administered daily subcutaneously (s.c., under the skin). When patients are randomised to concizumab prophylaxis they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week 0: arm 2, 3 \& 4) or visit 9a (week 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 (week 6: arm 2, 3 \& 4) or 9a.3 (week 30: arm 1) and will be based on the concizumab exposure level measured at the previous visit 4a (week 4) or 9a.2 (week 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 bypassing product until visit 9a (week 24: end of main part for arm 1).

Arm 3: Concizumab prophylaxis

The HAwI and HBwI patients enrolled into the concizumab phase 2 trial (NN7415-4310) at time of transfer will be offered enrolment into this trial. It is required that these patients are on concizumab prophylaxis up until enrolment into the trial. These patients will continue concizumab prophylaxis.

Group Type: EXPERIMENTAL

Concizumab

Intervention Type: DRUG

Concizumab will be administered daily subcutaneously (s.c., under the skin). When patients are randomised to concizumab prophylaxis they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week 0: arm 2, 3 \& 4) or visit 9a (week 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 (week 6: arm 2, 3 \& 4) or 9a.3 (week 30: arm 1) and will be based on the concizumab exposure level measured at the previous visit 4a (week 4) or 9a.2 (week 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 bypassing product until visit 9a (week 24: end of main part for arm 1).

Arm 4: Concizumab prophylaxis

Patients previously on prophylaxis with by-passing agents and on-demand patients who are screened at a timepoint where the required number of patients in arms 1 and 2 have been randomised. These patients will, if eligible, be enrolled into the trial and will initiate concizumab prophylaxis at visit 2a (week 0).

Group Type: EXPERIMENTAL

Concizumab

Intervention Type: DRUG

Concizumab will be administered daily subcutaneously (s.c., under the skin). When patients are randomised to concizumab prophylaxis they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week 0: arm 2, 3 \& 4) or visit 9a (week 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 (week 6: arm 2, 3 \& 4) or 9a.3 (week 30: arm 1) and will be based on the concizumab exposure level measured at the previous visit 4a (week 4) or 9a.2 (week 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 bypassing product until visit 9a (week 24: end of main part for arm 1).

Interventions

Concizumab

Concizumab will be administered daily subcutaneously (s.c., under the skin). When patients are randomised to concizumab prophylaxis they will receive a loading dose of 1.0 mg/kg concizumab at visit 2a (week 0: arm 2, 3 \& 4) or visit 9a (week 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 (week 6: arm 2, 3 \& 4) or 9a.3 (week 30: arm 1) and will be based on the concizumab exposure level measured at the previous visit 4a (week 4) or 9a.2 (week 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 bypassing product until visit 9a (week 24: end of main part for arm 1).

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 Haemophilia A or B of any severity with documented history of inhibitor (equal to or above 0.6 Bethesda Units (BU).
• Patient has been prescribed, or in need of, treatment with bypassing agents in the last 24 weeks prior to screening (for patients not previously enrolled in NN7415-4310 (explorer 4)).

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.
• Ongoing or planned Immune Tolerance Induction treatment.
• 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.)

• 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

Center for Inherited Blood Dis

Orange, California, United States

Children's Healthcare Atlanta

Atlanta, Georgia, United States

Indiana Hemophilia-Thromb Ctr

Indianapolis, Indiana, United States

Washington University School of Medicine_St. Louis

St Louis, Missouri, United States

St. Jude Affiliate Clinic at Novant Health Hemby Children's

Charlotte, North Carolina, United States

TriStar Medical Group Children's Specialist

Nashville, Tennessee, United States

University of Texas San Antonio

San Antonio, Texas, 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

Klin. Abt. f. Hämatologie und Hämostaseologie, AKH Wien

Vienna, , Austria

UMHAT Tsaritsa Yoanna - ISUL EAD, Pediatric clinical hematology and oncology

Sofia, , Bulgaria

Hamltn Hth Sci/McMstr Child Hosp

Hamilton, Ontario, Canada

KBC Zagreb, Rebro, Hemofilija centar

Zagreb, , Croatia

KBC Zagreb, Zavod za pedijatrijsku hematologiju

Zagreb, , Croatia

Ustav Hematologie a krevni tranfuze

Prague, , Czechia

Fakultni nemocnice v Motole

Prague, , Czechia

Skejby Blodsygdomme, blødercentret

Aarhus N, , Denmark

Hospices Civils de Lyon- Hopital Louis Pradel

Bron, , France

Centre Hospitalier de Clermont-Ferrand-Hopital Estaing

Clermont-Ferrand, , France

Ap-Hp-Hopital de Bicetre-1

Le Kremlin-Bicêtre, , France

Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou

Rennes, , France

St. John's Medical college and Hospital

Bangalore, Karnataka, India

Sahyadri Speciality Hospital

Pune, Maharashtra, India

Sahyadri Super Speciality Hospital

Pune, Maharashtra, India

All India Institute of Medical Sciences_New Dehli

New Dehli, New Delhi, India

CMCV

Ranipet, Tamil Nadu, India

CMCV

Ranipet, Tamil Nadu, India

All India Institute of Medical Sciences_New Dehli

New Delhi, , India

Dipartimento di Ematologia Univ. Firenze

Florence, FI, Italy

Istituto Oncologico Veneto - Oncoematologia IOV

Castelfranco Veneto, , Italy

Oncoematologia IOV

Castelfranco Veneto, , Italy

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

Milan, , Italy

Azienda OU "S.Maria della Misericordia"

Udine, , Italy

Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Donna Bambino Borgo Trento - U.O.C. Oncoematologia Pediatrica

Verona, , Italy

Ospedale Donna Bambino U.O.C. Oncoematologia Pediatrica

Verona, , Italy

Nagoya University Hospital_Blood Transfusion

Aichi, , Japan

Kagoshima City Hospital

Kagoshima, , Japan

St. Marianna University School of Medicine Hospital_Pediatrics

Kanagawa, , Japan

Mie University Hospital

Mie, , Japan

Nara Medical University Hospital_Pediatrics

Nara, , Japan

Saitama Medical Univ. Hospital

Saitama, , Japan

Ogikubo Hospital_Pediatries & Blood

Tokyo, , Japan

Hospital Pulau Pinang_Georgetown, Penang

George Town, Pulau Pinang, Malaysia

Hospital Queen Elizabeth 1

Kota Kinabalu, Sabah, Malaysia

Hospital Ampang

Ampang, Selangor, Malaysia

Hospital Ampang

Ampang, Selangor, , Malaysia

Hospital Universitario Dr. José Eleuterio González

Monterrey, Nuevo León, Mexico

Rikshospitalet - avdeling for blodsykdommer

Oslo, , Norway

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

SPSK nr 1 Klinika Hematoonkologii i Transplantacji Szpiku

Lublin, , Poland

Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku

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

Institute for Health Care of Children and Adolescents

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

Haematology Clinic

Durban, KwaZulu-Natal, South Africa

Pietersburg Hospital

Polokwane, Limpopo, South Africa

Daejeon Eulji Medical Center, Eulji University

Daejeon, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Regional Universitario de Málaga

Málaga, , Spain

Hospital Universitario Regional de Málaga

Málaga, , Spain

Hospital Central de Asturias

Oviedo, , Spain

Hospital Univ. Central de Asturias

Oviedo, , Spain

Hospital Virgen del Rocío

Seville, , Spain

Koagulationsmottagning

Malmo, , Sweden

Koagulationsmottagningen

Solna, , Sweden

Sunpasitthiprasong Hospital_Pediatrics Department

Ubon Ratchathani, Mueang Distirct,, Thailand

Ramathibodi Hospital_Department of Haematology

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai Hospital _Pediatric Hematology and Oncology

Chiang Mai, , Thailand

İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Onkoloji Enstitüsü

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

Akdeniz Üniversitesi Hastanesi- Hematoloji

Antalya, Konyaaltı/ Antalya, Turkey (Türkiye)

Acıbadem Adana Hastanesi-Hematoloji

Adana, , Turkey (Türkiye)

Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji

Adana, , 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

West Midlands Adult Comprehensive Care Haemophilia

Birmingham, , United Kingdom

Great Ormond Street Hospital for Children

London, , United Kingdom

Manchester Royal Infirmary_Manchester

Manchester, , United Kingdom

Queen's Medical Centre - Haemophilia Comprehensive Care Centre

Nottingham, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Countries

United States; Algeria; Australia; Austria; Bulgaria; Canada; Croatia; Czechia; Denmark; France; India; Italy; Japan; Malaysia; Mexico; Norway; Poland; Portugal; Russia; Serbia; Slovakia; South Africa; South Korea; Spain; Sweden; Thailand; Turkey (Türkiye); Ukraine; United Kingdom

References

Tran H, von Mackensen S, Abraham A, Castaman G, Hampton K, Knoebl P, Linari S, Odgaard-Jensen J, Neergaard JS, Stasyshyn O, Thaung Zaw JJ, Zulfikar B, Shapiro A. Concizumab prophylaxis in persons with hemophilia A or B with inhibitors: patient-reported outcome results from the phase 3 explorer7 study. Res Pract Thromb Haemost. 2024 Jun 17;8(4):102476. doi: 10.1016/j.rpth.2024.102476. eCollection 2024 May.

Reference Type: DERIVED

PMID: 39099801 (View on PubMed)

Matsushita T, Shapiro A, Abraham A, Angchaisuksiri P, Castaman G, Cepo K, d'Oiron R, Frei-Jones M, Goh AS, Haaning J, Hald Jacobsen S, Mahlangu J, Mathias M, Nogami K, Skovgaard Rasmussen J, Stasyshyn O, Tran H, Vilchevska K, Villarreal Martinez L, Windyga J, You CW, Zozulya N, Zulfikar B, Jimenez-Yuste V; explorer7 Investigators. Phase 3 Trial of Concizumab in Hemophilia with Inhibitors. N Engl J Med. 2023 Aug 31;389(9):783-794. doi: 10.1056/NEJMoa2216455.

Reference Type: DERIVED

PMID: 37646676 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1225-9670

Identifier Type: OTHER

Identifier Source: secondary_id

2018-004889-34

Identifier Type: REGISTRY

Identifier Source: secondary_id

NN7415-4311

Identifier Type: -

Identifier Source: org_study_id