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

NCT04082429 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: NN7415-4307U1111-1225-97222018-004891-36
• Study Type: interventional
• Target: 156
• Locations: 31 countries
• Sites: 107

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

Outcome Measures

Primary Outcomes (2)

• Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes

  Rate of treated spontaneous and traumatic bleeding episodes for haemophilia A participants without inhibitors is presented. The observation period used for reporting this endpoint is on-treatment without ancillary therapy excluding data before restart (OTwoATexBR). It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of annualised bleeding rate (ABR). Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.

  On demand (arm 1): From week 0 up until start of concizumab treatment (week 24); Concizumab (arm 2): From week 0 up until the confirmatory analyses cut-off

• Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes

  Rate of treated spontaneous and traumatic bleeding episodes for haemophilia B participants without inhibitors is presented. The observation period used for reporting this endpoint is OTwoATexBR. It is defined as the time period after the restart where participants are treated by concizumab treatment or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleeding episode. The data is reported in the terms of ABR. Week 0 is defined as time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. Confirmatory analyses cut-off was defined as when all participants on no PPX (arm 1) had completed the 24-week visit or withdrawn and all participants on concizumab PPX (in arms 2 and 4) had completed the 32-week visit or withdrawn.

  On demand (arm 1): From week 0 up until start of concizumab treatment (week 24); Concizumab (arm 2): From week 0 up until the confirmatory analyses cut-off

Secondary Outcomes (21)

• Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes

  For previous PPX (study 4322): After an initial period on PPX treatment of at least 24 weeks until end of study (maximum 115 weeks) For concizumab PPX (trial 4307): After an initial 5-8 weeks dose adjustment period and up until 56 week cut off

• Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Bleeding Episodes

  For previous PPX (study 4322): After an initial period on PPX treatment of at least 24 weeks until end of study (maximum 115 weeks) For concizumab PPX (trial 4307): After an initial 5-8 weeks dose adjustment period and up until 56 week cut off

• Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes

  On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off

• Haemophilia B Participants Without Inhibitors: Rate of Treated Spontaneous Bleeding Episodes

  On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off

• Haemophilia A Participants Without Inhibitors: Rate of Treated Spontaneous and Traumatic Joint Bleeding Episodes

  On demand (arm 1): From randomisation after the pause (week 0) up until start of concizumab treatment (week 24) Concizumab (arm 2): From start of the new concizumab dosing regimen (week 0) up until the 56 week cut-off

Study Arms (4)

Arm 1: No prophylaxis (PPX)

EXPERIMENTAL

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.

Drug: Concizumab

Arm 2: Concizumab prophylaxis

EXPERIMENTAL

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

Drug: Concizumab

Arm 3: Concizumab prophylaxis

EXPERIMENTAL

The HA patients enrolled into the concizumab phase 2 trial NN7415-4255 (explorer 5) will be offered enrolment into this arm.

Drug: Concizumab

Arm 4: Concizumab prophylaxis

EXPERIMENTAL

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.

Drug: Concizumab

Interventions

Concizumab 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 1: No prophylaxis (PPX); Arm 2: Concizumab prophylaxis; Arm 3: Concizumab prophylaxis; Arm 4: Concizumab prophylaxis

Eligibility Criteria

• Age: 12 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%).

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (112)

Children's Hospital Los Angeles - Endocrinology

Los Angeles, California, 90027, United States

Location

Center for Inherited Blood Disorders

Orange, California, 92868, United States

Location

Center for Blood Disorders Augusta University

Augusta, Georgia, 30912, United States

Location

Indiana Hemophilia-Thromb Ctr

Indianapolis, Indiana, 46260, United States

Location

University of Iowa_Iowa City

Iowa City, Iowa, 52242, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Michigan State University

Lansing, Michigan, 48911, United States

Location

Novant Hlth Vasc Ins Charlotte

Charlotte, North Carolina, 28204, United States

Location

M.S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Vanderbilt University Medical Center_Nashville_0

Nashville, Tennessee, 37212, United States

Location

University of Texas San Antonio

San Antonio, Texas, 78229, United States

Location

Versiti, CCBD

Milwaukee, Wisconsin, 53226, United States

Location

Haematology and Blood Bank Department

Algiers, 16000, Algeria

Location

CHU Constantine BEN BADIS/ Hematology department

Constantine, 25000, Algeria

Location

The Alfred

Melbourne, Victoria, 3004, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Fiona Stanley Hospital - Haemophilia and Haemostasis Centre

Murdoch, Western Australia, 6150, Australia

Location

University Clinical Center of Republic Srpska (205)

Banja Luka, 78000, Bosnia and Herzegovina

Location

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

Sofia, 1527, Bulgaria

Location

UMHAT Sveta Marina EAD, Clinic of Pediatric Clinical Hematology and Oncology

Varna, 9010, Bulgaria

Location

Eastern Health Authority

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

Location

Hamltn Hth Sci/McMstr Child Hosp

Hamilton, Ontario, L8N 3Z5, Canada

Location

KBC Zagreb_Hematology

Zagreb, 10 000, Croatia

Location

Copenhagen Center for Heamatology

Copenhagen, 2100, Denmark

Location

North Estonia Medical Centre Foundation

Tallinn, 13419, Estonia

Location

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

Brest, 29200, France

Location

CHU de Caen - Côte de Nacre

Caen, 14033, France

Location

Hopital de Bicetre

Le Kremlin-Bicêtre, 94270, France

Location

Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu

Nantes, 44093, France

Location

Hôpital Pontchaillou

Rennes, 35033, France

Location

Centre Hospitalier Universitaire de Saint Etienne-Hopital Nord

Saint-Priest-en-Jarez, 42270, France

Location

Universitätsklinikum Bonn - Institut für Experimentelle Hämatologie

Bonn, 53127, Germany

Location

Universität des Saarlandes - Hämostaseologie und Transfusionsmedizin

Homburg, 66424, Germany

Location

MH Eü. Központ -Orszagos Haemophilia Kozpont

Budapest, H-1134, Hungary

Location

St. John's Medical college and Hospital

Bangalore, Karnataka, 560034, India

Location

Sahyadri Speciality Hospital

Pune, Maharashtra, 411004, India

Location

Sahyadri Super Speciality Hospital

Pune, Maharashtra, 411004, India

Location

J K Lon Hospital

Jaipur, Rajasthan, 302004, India

Location

CMCV

Ranipet, Tamil Nadu, 632517, India

Location

Sheba MC The Israeli National Hemophilia Center

Tel Litwinsky, 52621, Israel

Location

Dipartimento di Ematologia Univ. Firenze

Florence, FI, 50134, Italy

Location

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

Milan, MI, 20124, Italy

Location

Policlinico Umberto I Sezione Ematologia

Roma, 00161, Italy

Location

A.O.U Città Salute Scienza Torino

Torino, 10126, Italy

Location

Nagoya University Hospital_Blood Transfusion

Aichi, 466-8560, Japan

Location

Hiroshima University Hospital, Hematology

Hiroshima, 734-8551, Japan

Location

Hiroshima University Hospital_Hematology

Hiroshima, 734-8551, Japan

Location

Hyogo prefectural kobe children's hospital Dept. of Haem and Onclogy

Hyōgo, 654-0047, Japan

Location

Hyogo prefectural kobe children's hospital

Hyōgo, 654-0047, Japan

Location

Itoigawa sogo Hospital_Department of Pediatrics

Niigata, 941-8502, Japan

Location

Osaka National Hospital_Dept. of Infectious diseases

Osaka, 546-0006, Japan

Location

Saitama Children's Med Centre_Hematology-Oncology

Saitama, 330-8777, Japan

Location

Saitama Medical Univ. Hospital_Dep of Int Med, Cent for Hemo

Saitama, 350-0495, Japan

Location

Saitama Medical Univ. Hospital

Saitama, 350-0495, Japan

Location

Shizuoka Children's Hospital, Hematology-Oncology

Shizuoka, 420-8660, Japan

Location

Shizuoka Children's Hospital

Shizuoka, 420-8660, Japan

Location

National Center for Child Health and Development_Hematology

Tokyo, 157-8535, Japan

Location

Ogikubo Hospital_Pediatries & Blood

Tokyo, 167-0035, Japan

Location

Children Oncohaematology department Children's Hospital,

Vilnius, 08406, Lithuania

Location

Vilnius University hospital Santaros klinikos

Vilnius, LT-08661, Lithuania

Location

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

Location

Hospital Ampang

Ampang, Selangor, 68000, Malaysia

Location

Hospital Universitario Dr. José Eleuterio González

Monterrey, Nuevo León, 64460, Mexico

Location

Uniwersytecki Szpital Kliniczny W Poznaniu

Poznan, Greater Poland Voivodeship, 60-569, Poland

Location

Szpital Uniwersytecki, Oddzial Kliniczny Hematologii

Krakow, Lesser Poland Voivodeship, 30-688, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, Masovian Voivodeship, 02-776, Poland

Location

Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku

Lublin, 20-081, Poland

Location

Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa

Lublin, 20-093, Poland

Location

Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu

Wroclaw, 50-367, Poland

Location

ULS São João, E.P.E.

Porto, 4200-319, Portugal

Location

Children Regional Clinical Hospital

Krasnodar, 350007, Russia

Location

Morozovskaya municipal children hospital

Moscow, 119049, Russia

Location

National Medical Research institution of haemotology

Moscow, 125167, Russia

Location

Republican Hospital n.a. V. A. Baranov

Petrozavodsk, 185019, Russia

Location

City out-patient clinic 37, City Hemophilia Centre

Saint Petersburg, 191186, Russia

Location

Clinical Centre of Serbia, Institute for Haematology

Belgrade, 11000, Serbia

Location

Institute for Mother and Child Health Care of Serbia

Belgrade, 11070, Serbia

Location

University Clinical Centre Kragujevac

Kragujevac, 34000, Serbia

Location

Clinical Centre of Vojvodina

Novi Sad, 21000, Serbia

Location

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

Bratislava, 851 07, Slovakia

Location

Charlotte Maxeke Johannesburg Academic Hospital

Parktown, Johannesburg, Gauteng, 2193, South Africa

Location

Pietersburg Hospital

Polokwane, Limpopo, 0699, South Africa

Location

Daejeon Eulji Medical Center, Eulji University

Daejeon, 35233, South Korea

Location

Daejeon Eulji University Hospital

Daejeon, 35233, South Korea

Location

Jeju National University Hospital

Jeju City, 63241, South Korea

Location

Jeju National University Hospital

Jeju-do, 63241, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Univ. Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46026, Spain

Location

Koagulationsmottagning - SUS

Malmo, 214 28, Sweden

Location

Koagulationsmottagningen

Solna, 171 64, Sweden

Location

Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie

Zurich, 8091, Switzerland

Location

Ramathibodi Hospital_Department of Haematology

Bangkok, 10400, Thailand

Location

Gazi University

Ankara, Beşevler/Ankara, 06500, Turkey (Türkiye)

Location

Gazi Üniversitesi Hastanesi- Hematoloji

Ankara, Beşevler/Ankara, 06500, Turkey (Türkiye)

Location

İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Onkoloji Enstitüsü

Capa-ISTANBUL, Capa-ISTANBUL, 34093, Turkey (Türkiye)

Location

Acıbadem Adana Hastanesi-Hematoloji

Adana, 01130, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty

Ankara, 06230, Turkey (Türkiye)

Location

Hacettepe Üniversitesi Hastanesi- Endokrinoloji

Ankara, 06230, Turkey (Türkiye)

Location

Trakya Üniversitesi Tıp Fakültesi Hastanesi-Hematoloji

Edirne, 22030, Turkey (Türkiye)

Location

Ege Üniversitesi Hastanesi- Hematoloji

Izmir, 35100, Turkey (Türkiye)

Location

Ondokuz Mayıs Üniversitesi Hastanesi - Hematoloji

Samsun, 55139, Turkey (Türkiye)

Location

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

Kyiv, 01135, Ukraine

Location

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

Lviv, 79044, Ukraine

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Royal Free Haemophilia Comprehensive Care Center

London, NW3 2QG, United Kingdom

Location

Royal Free Hospital - Haemophilia

London, NW3 2QG, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40166710 DERIVED

• 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.

  PMID: 39521008 DERIVED

MeSH Terms

Interventions

concizumab

Limitations and Caveats

There was a pause in the concizumab clinical development programme during the period from March to August 2020, while thromboembolic events were investigated. As of 19 March 2020, all participants on concizumab had stopped treatment and switched to another available treatment as per investigator's discretion. Based on the investigation, risk mitigation actions (including new concizumab dosing regimen) were implemented and trial protocols updated before resuming.

Results Point of Contact

• Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S

clinicaltrials@novonordisk.com

(+1) 866-867-7178

Study Officials

• Clinical Reporting Anchor and Disclosure (1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Patients will be randomised to concizumab PPX/no PPX/ assigned into non-randomised arms, based on treatment before trial. Upon restart, patients randomised to arms 1/2 before pause will enter arm 4. Patients allocated to arms 3 \& 4 before pause will re-enter initially allocated arm. Randomisation into arms 1/2 will be restarted with new patients. Main part is completed when patient completed 24 wks (excluding screening) in arm 1 or 32 wks (excluding screening) in arms 2-4. After main part, patients will have offer to continue in extension (ext.) part and receive treatment with product until concizumab is commercially available in their countries or until 31-Dec-2027 at latest. Patients will be in the extension part for up to 345 weeks (arms 2-4) or up to 353 weeks (arm 1). Patient will receive last dose at home on day prior to visit 26a. Follow-up part will start on visit 26a and lasts for 7 wks and include reporting of bleeding episodes until visit 27a.

Study Record Dates

• First Submitted: September 5, 2019
• First Posted: September 9, 2019
• Study Start: November 13, 2019
• Primary Completion: July 12, 2022
• Study Completion (Estimated): February 21, 2028
• Last Updated: March 24, 2026
• Results First Posted: October 31, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

DE (2); UA (2); SE (2); CR (1); HU (1); JP (14); ME (1); RU (5); CA (2); KR (5); CH (1); US (12); IT (4); DK (1); ES (5); BO (1); PL (6); SL (1); PT (1); IL (1); AU (4); IN (5); TU (9); FR (6); TH (1); BU (2); MY (2); AL (2); GB (4); LI (2); ZA (2)