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

Phase 3

Active, not recruiting

• Conditions: Haemophilia B Without Inhibitors; Haemophilia A Without Inhibitors
• Interventions: Drug: Concizumab

• Registration Number: NCT04082429
• 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 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 6.5 years. The length of time the participant will be in the study depends on when they agreed to take part or when the medicine is available for purchase in their country (21 April 2026 at the latest). Participants will have to come to the clinic for up to 40 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. 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-05
• Study First Submitted QC: 2019-09-05
• Study First Posted: 2019-09-09
• Study Start: 2019-11-13
• Primary Completion: 2022-07-12
• Disposition First Submitted: 2023-07-10
• Disposition First Posted: 2023-07-13
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-13
• Last Update Posted: 2024-12-16
• Study Completion: 2026-06-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 158

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%).

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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.
• 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.)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 3: Concizumab prophylaxis	Concizumab	The HA patients enrolled into the concizumab phase 2 trial NN7415-4255 (explorer 5) will be offered enrolment into this arm.
Arm 2: Concizumab prophylaxis	Concizumab	HA and HB patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis.
Arm 1: No prophylaxis (PPX)	Concizumab	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.
Arm 4: Concizumab prophylaxis	Concizumab	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.

Primary Outcome Measures

Name	Time	Method
For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes	On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes	On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.

Secondary Outcome Measures

Name	Time	Method
For haemophilia B patients without inhibitors: Number of treated spontaneous bleeding episodes	On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
For haemophilia A patients without inhibitors: Number of treated spontaneous bleeding episodes	On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds	On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
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 296 weeks).	This will be presented as 'count of injection site reactions'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous 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 296 weeks).	This will be presented as 'count of participants'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day).
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'.
For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes	Time frame is presented under 'outcome measure description'	This will be presented as 'count of episodes'. Arm 4 patients who have been on stable PPX at least 24 weeks in study 4322. For previous PPX (study 4322): From the point in time where PPX is stable and up until the end of study. Stable is defined as the time after an initial period on PPX treatment of at least 24 weeks. For concizumab PPX (trial 4307): From the point in time where the concizumab maintenance dose is confirmed, increased or decreased and up until the confirmatory analyses cut-off (at least 24 weeks).
For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes	Time frame is presented under 'outcome measure description'	This will be presented as 'count of episodes'. Arm 4 patients who have been on stable PPX at least 24 weeks in study 4322. For previous PPX (study 4322): From the point in time where PPX is stable and up until the end of study. Stable is defined as the time after an initial period on PPX treatment of at least 24 weeks. For concizumab PPX (trial 4307): From the point in time where the concizumab maintenance dose is confirmed, increased or decreased and up until the confirmatory analyses cut-off (at least 24 weeks).
For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds	On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds	On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses cut-off (at least 32 weeks)	This will be presented as 'count of episodes'.
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 free tissue factor pathway inhibitor (TFPI) concentration	Prior to the concizumab administration at week 24 (after restart)	This will be measured in 'ng/mL'.
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 296 weeks).	This will be presented as 'count of events'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day).
Pre-dose thrombin peak	Prior to the concizumab administration at week 24 (after restart)	This will be measured in 'nmol/L'.
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'.
For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds	On demand (arm 1): From randomisation after the pause (Wk 0) up until start of concizumab treatment (Wk 24). Concizumab (arm 2): From start of the new concizumab dosing regimen (Wk 0) up until the confirmatory analyses 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 296 weeks).	This will be presented as 'count of hypersensitivity type reactions'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day).

Trial Locations

Locations (80)

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

Sheba MC The Israeli National Hemophilia Center; 🇮🇱 Tel-Hashomer, Israel

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; 🇯🇵 Hyogo, 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; 🇯🇵 Shizuoka, Japan

National Center for Child Health and Development_Hematology; 🇯🇵 Tokyo, Japan

National Center for Child Health and Development; 🇯🇵 Tokyo, Japan

Ogikubo Hospital_Pediatries & Blood; 🇯🇵 Tokyo, Japan

Daejeon Eulji University Hospital; 🇰🇷 Daejeon, Korea, Republic of

Jeju National University Hospital; 🇰🇷 Jeju-do, Korea, Republic of

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

Children Oncohaematology department Children's Hospital,; 🇱🇹 Vilnius, Lithuania

Vilnius University hospital Santaros klinikos; 🇱🇹 Vilnius, Lithuania

Hospital Ampang; 🇲🇾 Ampang, Selangor, Malaysia

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

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

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

Hopital de Bicetre; 🇫🇷 Le Kremlin Bicetre, France

Hôpital Pontchaillou; 🇫🇷 Rennes, France

UKS - Hämostaseologie und Transfusionsmedizin; 🇩🇪 Homburg, Germany

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

Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie; 🇨🇭 Zürich, Switzerland

Children's Hospital Los Angeles - Endocrinology; 🇺🇸 Los Angeles, California, United States

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

Children's Hospital of Michigan; 🇺🇸 Detroit, Michigan, 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"; 🇧🇬 Sofia, Bulgaria

Hamltn Hth Sci/McMstr Child Hosp; 🇨🇦 Hamilton, Ontario, Canada

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

Copenhagen Center for Heamatology; 🇩🇰 København, 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

Uniwersytecki Szpital Kliniczny W Poznaniu; 🇵🇱 Poznań, Wielkopolskie, 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

Institute for Mother and Child Health Care of Serbia; 🇷🇸 Belgrade, Serbia

University Clinical Centre Kragujevac; 🇷🇸 Kragujevac, Serbia

Clinical Centre of Vojvodina; 🇷🇸 Novi Sad, Serbia

Pietersburg Hospital; 🇿🇦 Polokwane, Limpopo, South Africa

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Regional de Málaga; 🇪🇸 Málaga, Spain

Hospital Virgen del Rocío; 🇪🇸 Sevilla, Spain

Koagulationsmottagning; 🇸🇪 Malmö, Sweden

Koagulationsmottagningen; 🇸🇪 Solna, Sweden

Ramathibodi Hospital_Bangkok_0; 🇹🇭 Bangkok, Thailand

Gazi University; 🇹🇷 Ankara, Beşevler/Ankara, Turkey

Acibadem Adana Hastanesi; 🇹🇷 Adana, Turkey

Hacettepe University Medical Faculty; 🇹🇷 Ankara, Turkey

Trakya University; 🇹🇷 Edirne, Turkey

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

Ege Universitesi Tip Fakultesi; 🇹🇷 Izmir, Turkey

Ondokuz Mayis University Medical Faculty Ped. Haematology; 🇹🇷 Samsun, Turkey

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

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

Belfast City Hospital; 🇬🇧 Belfast, United Kingdom

Royal Free Haemophilia Comprehensive Care Center; 🇬🇧 London, United Kingdom

Royal Hallamshire Hospital; 🇬🇧 Sheffield, United Kingdom