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

Phase 3

Active, not recruiting

• Conditions: Haemophilia A With Inhibitors; Haemophilia B With Inhibitors
• Interventions: Drug: Concizumab

• Registration Number: NCT04083781
• Lead Sponsor: Novo Nordisk A/S

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 six 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 (12 November 2025 at the latest). Participants will have to come to the clinic for up to 41 times. 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-06
• Study First Submitted QC: 2019-09-06
• Study First Posted: 2019-09-10
• Study Start: 2019-10-21
• Primary Completion: 2021-12-27
• Disposition First Submitted: 2022-12-21
• Disposition First Submitted QC: 2022-12-21
• Disposition First Posted: 2022-12-27
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-20
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 136

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)).

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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.)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1: No prophylaxis	Concizumab	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.
Arm 2: Concizumab prophylaxis	Concizumab	HAwI and HBwI patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.
Arm 3: Concizumab prophylaxis	Concizumab	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.
Arm 4: Concizumab prophylaxis	Concizumab	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).

Primary Outcome Measures

Name	Time	Method
The number of treated spontaneous and traumatic bleeding episodes	On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks). Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.

Secondary Outcome Measures

Name	Time	Method
Number of treated spontaneous and traumatic joint bleeds	On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
Number of treated spontaneous bleeding episodes	On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
Number of thromboembolic events	Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 280 weeks).	This will be presented as 'count of thromboembolic events'. Week 0, before the pause is defined as the time of randomisation to on-demand administration or time of start of the initial concizumab dosing regimen (0.25 mg/kg/day).
Maximum concizumab plasma concentration (Cmax)	From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)	This will be measured in 'ng/mL'.
Change in 36 Item short form health survey version 2 (SF36v2) bodily pain	From start of treatment (week 0) until week 24. Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.	This will be presented as 'score on a scale'. The bodily pain subscale of the SF-36v2 questionnaire consists of 2 items. Subscale scores range from 0-100 and are transformed into population norm adjusted T-scores. A higher score indicates a better outcome on this subscale.
Change in SF36v2 physical functioning	From start of treatment (week 0) until week 24. Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.	This will be presented as 'score on a scale'. The physical function subscale of the SF-36v2 questionnaire consists of 1 item with 10 subitems. Subscale scores range from 0-100 and are transformed into population norm adjusted T-scores. A higher score indicates a better outcome on this subscale.
Number of treated spontaneous and traumatic target joint bleeds	On demand (arm 1): From randomisation (week 0) up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the primary analysis cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
Number of hypersensitivity type reactions	Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 280 weeks).	This will be presented as 'count of hypersensitivity type reactions'. Week 0, before the pause is defined as the time of randomisation to on-demand administration or time of start of the initial concizumab dosing regimen (0.25 mg/kg/day).
Number of injection site reactions	Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 280 weeks).	This will be presented as 'count of injection site reactions'. Week 0, before the pause is defined as the time of randomisation to on-demand administration or time of start of the initial concizumab dosing regimen (0.25 mg/kg/day).
Number of patients with antibodies to concizumab	Concizumab: Before the pause: From start of treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment up until the end of trial (up to 280 weeks).	This will be presented as 'count of patients'. Week 0, before the pause is defined as the time of randomisation to on-demand administration or time of start of the initial concizumab dosing regimen (0.25 mg/kg/day).
Pre-dose (trough) concizumab plasma concentration (Ctrough)	Prior to the concizumab administration at week 24 (after restart)	This will be measured in 'ng/mL'.
Pre-dose thrombin peak	Prior to the concizumab administration at week 24 (after restart)	This will be measured in 'nmol/L'.
Pre-dose free tissue factor pathway inhibitor (TFPI) concentration	Prior to the concizumab administration at week 24 (after restart)	This will be measured in 'ng/mL'.
Area under the concizumab plasma concentration-time curve (AUC)	From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)	This will be measured in 'ng\*hr/mL'.

Trial Locations

Locations (79)

St. Marianna University School of Medicine Hospital_Pediatrics; 🇯🇵 Kanagawa, Japan

Nara Medical University Hospital_Pediatrics; 🇯🇵 Nara, Japan

Saitama Medical Univ. Hospital; 🇯🇵 Saitama, Japan

Ogikubo Hospital_Pediatries & Blood; 🇯🇵 Tokyo, Japan

Daejeon Eulji Medical Center, Eulji University; 🇰🇷 Daejeon, Korea, Republic of

Severance Hospital, Yonsei University Health System; 🇰🇷 Seoul, Korea, Republic of

Hospital Queen Elizabeth 1; 🇲🇾 Kota Kinabalu, Sabah, Malaysia

West Midlands Adult Comprehensive Care Haemophilia; 🇬🇧 Birmingham, United Kingdom

Children's Healthcare Atlanta; 🇺🇸 Atlanta, Georgia, United States

The Alfred; 🇦🇺 Melbourne, Victoria, Australia

Hospital Ampang; 🇲🇾 Ampang, Selangor, Malaysia

Hospital Pulau Pinang_Georgetown, Penang; 🇲🇾 Georgetown, Penang, Malaysia

Hospital Universitario Dr. José Eleuterio González; 🇲🇽 Monterrey, Nuevo León, Mexico

Rikshospitalet - avdeling for blodsykdommer; 🇳🇴 Oslo, Norway

Indiana Hemophilia-Thromb Ctr; 🇺🇸 Indianapolis, Indiana, United States

Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku; 🇵🇱 Lublin, Poland

Center for Inherited Blood Dis; 🇺🇸 Orange, California, United States

Washington University School of Medicine_St. Louis; 🇺🇸 Saint 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

Fiona Stanley Hospital - Haemophilia and Haemostasis Centre; 🇦🇺 Murdoch, Western Australia, Australia

Klin. Abt. f. Hämatologie und Hämostaseologie, AKH Wien; 🇦🇹 Wien, Austria

UMHAT "Tsaritsa Yoanna-ISUL"; 🇧🇬 Sofia, Bulgaria

KBC Zagreb, Rebro, Hemofilija centar; 🇭🇷 Zagreb, Croatia

KBC Zagreb, Zavod za pedijatrijsku hematologiju; 🇭🇷 Zagreb, Croatia

Ustav Hematologie a krevni tranfuze; 🇨🇿 Praha 2, Czechia

Fakultni nemocnice v Motole; 🇨🇿 Praha, Czechia

Skejby Blodsygdomme, blødercentret; 🇩🇰 Aarhus N, Denmark

Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1; 🇫🇷 Bron, France

Centre Hospitalier de Clermont-Ferrand-Hopital Estaing; 🇫🇷 Clermont-Ferrand, France

Ap-Hp-Hopital de Bicetre-1; 🇫🇷 Le Kremlin-Bicetre, 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 Delhi, India

CMCV; 🇮🇳 Ranipet, Tamil Nadu, India

Dipartimento di Ematologia Univ. Firenze; 🇮🇹 Firenze, FI, Italy

Oncoematologia IOV; 🇮🇹 Castelfranco Veneto, Italy

Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano; 🇮🇹 Milano, Italy

Azienda OU "S.Maria della Misericordia"; 🇮🇹 Udine, Italy

Ospedale Donna Bambino U.O.C. Oncoematologia Pediatrica; 🇮🇹 Verona, Italy

Nagoya University Hospital_Blood Transfusion; 🇯🇵 Aichi, Japan

Kagoshima City Hospital; 🇯🇵 Kagoshima, Japan

Intytut Hematologii i Transfuzjologii; 🇵🇱 Warszawa, Mazowieckie, Poland

Szpital Uniwersytecki, Oddzial Kliniczny Hematologii; 🇵🇱 Kraków, Małopolskie, Poland

SPSK nr 1 Klinika Hematoonkologii i Transplantacji Szpiku; 🇵🇱 Lublin, Poland

Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu; 🇵🇱 Wroclaw, Poland

Centro Hospitalar de São João_Porto; 🇵🇹 Porto, Portugal

Children Regional Clinical Hospital; 🇷🇺 Krasnodar, Russian Federation

Morozovskaya municipal children hospital; 🇷🇺 Moscow, Russian Federation

National Medical Research institution of haemotology; 🇷🇺 Moscow, Russian Federation

Republican Hospital n.a. V. A. Baranov; 🇷🇺 Petrozavodsk, Russian Federation

City out-patient clinic 37, City Hemophilia Centre; 🇷🇺 Saint-Petersburg, Russian Federation

University Clinical Centre Kragujevac; 🇷🇸 Kragujevac, 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

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Regional de Málaga; 🇪🇸 Málaga, Spain

Hospital Central de Asturias; 🇪🇸 Oviedo, Spain

Hospital Virgen del Rocío; 🇪🇸 Sevilla, Spain

Koagulationsmottagningen; 🇸🇪 Solna, Sweden

Ramathibodi Hospital_Bangkok_0; 🇹🇭 Bangkok, Thailand

Hematology and Oncology, Dept.of Pediatrics, CMU; 🇹🇭 Chiang Mai, Thailand

Sunpasitthiprasong Hospital; 🇹🇭 Ubon Ratchathani, Thailand

Acibadem Adana Hastanesi; 🇹🇷 Adana, Turkey

Cukurova Universitesi; 🇹🇷 Adana, Turkey

Akdeniz Universitesi; 🇹🇷 Antalya, Turkey

Istanbul University Oncology Institute; 🇹🇷 Capa-ISTANBUL, Turkey

National specialized children clinic "OHMATDYT"; 🇺🇦 Kyiv, Ukraine

Institute of blood pathology and transfusion medicine; 🇺🇦 Lviv, Ukraine

Great Ormond Street Hospital for Children; 🇬🇧 London, United Kingdom

Royal Hallamshire Hospital; 🇬🇧 Sheffield, United Kingdom