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

NCT04083781 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: NN7415-4311U1111-1225-96702018-004889-34
• Study Type: interventional
• Target: 134
• Locations: 27 countries
• Sites: 93

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 B With Inhibitors; Haemophilia A With Inhibitors

Outcome Measures

Primary Outcomes (1)

• Rate of Treated Spontaneous and Traumatic Bleeding Episodes

  Rate of treated spontaneous and traumatic bleeding episodes is presented. The observation period used for reporting this endpoint is on-treatment without ancillary therapy excl. data on initial regimen for participants exposed to both regimens (OTwoATexIR). It is defined as the time period where participants are treated by either the new concizumab dosing regimen or the initial concizumab dosing regimen (only included if not exposed to the new concizumab dosing regimen) or are treated by on-demand treatment and additionally have not used factor-containing products not related to treatment of a bleed during any of the cases. The data is reported in the terms of annualised bleeding rate (ABR). Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.

  On demand (arm 1): From week 0 up until start of concizumab treatment (at least 24 weeks) Concizumab (arm 2): From week 0 up until the primary analysis cut-off (at least 32 weeks)

Secondary Outcomes (18)

• Rate of Treated Spontaneous Bleeding Episodes

  On demand (arm 1): From week 0 up until start of concizumab treatment (at least 24 weeks) Extension concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off Concizumab (arm 2): From week 0 up until week 56 cut-off

• Rate of Treated Spontaneous and Traumatic Joint Bleeds

  On demand (arm 1): From week 0 up until start of concizumab treatment (at least 24 weeks) Extension concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off Concizumab (arm 2): From week 0 up until week 56 cut-off

• Rate of Treated Spontaneous and Traumatic Target Joint Bleeds

  On demand (arm 1): From week 0 up until start of concizumab treatment (at least 24 weeks) Extension concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off Concizumab (arm 2): From week 0 up until week 56 cut-off

• Change in 36-item Short Form Health Survey (SF-36v2) Bodily Pain

  Baseline (week 0), Week 24

• Change in SF36v2 Physical Functioning

  Baseline (week 0), Week 24

Study Arms (4)

Arm 1: No prophylaxis

EXPERIMENTAL

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.

Drug: Concizumab

Arm 2: Concizumab prophylaxis

EXPERIMENTAL

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

Drug: Concizumab

Arm 3: Concizumab prophylaxis

EXPERIMENTAL

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.

Drug: Concizumab

Arm 4: Concizumab prophylaxis

EXPERIMENTAL

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).

Drug: Concizumab

Interventions

Concizumab 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 1: No prophylaxis; Arm 2: Concizumab prophylaxis; Arm 3: Concizumab prophylaxis; Arm 4: Concizumab prophylaxis

Eligibility Criteria

• 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 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)).

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.
• 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.)

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (99)

Center for Inherited Blood Dis

Orange, California, 92868, United States

Location

Children's Healthcare Atlanta

Atlanta, Georgia, 30329, United States

Location

Indiana Hemophilia-Thromb Ctr

Indianapolis, Indiana, 46260, United States

Location

Washington University School of Medicine_St. Louis

St Louis, Missouri, 63110, United States

Location

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

Charlotte, North Carolina, 28204, United States

Location

TriStar Medical Group Children's Specialist

Nashville, Tennessee, 37203, United States

Location

University of Texas San Antonio

San Antonio, Texas, 78229, 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

The Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Fiona Stanley Hospital - Haemophilia and Haemostasis Centre

Murdoch, Western Australia, 6150, Australia

Location

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

Vienna, 1090, Austria

Location

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

Sofia, 1527, Bulgaria

Location

Hamltn Hth Sci/McMstr Child Hosp

Hamilton, Ontario, L8N 3Z5, Canada

Location

KBC Zagreb, Rebro, Hemofilija centar

Zagreb, 10 000, Croatia

Location

KBC Zagreb_Hematology

Zagreb, 10 000, Croatia

Location

KBC Zagreb, Zavod za pedijatrijsku hematologiju

Zagreb, 10000, Croatia

Location

Ustav Hematologie a krevni tranfuze

Prague, 12000, Czechia

Location

Fakultni Nemocnice Motol A Homolka

Prague, 150 18, Czechia

Location

Skejby Blodsygdomme, blødercentret

Aarhus N, 8200, Denmark

Location

Hospices Civils de Lyon- Hopital Louis Pradel

Bron, 69500, France

Location

Centre Hospitalier de Clermont-Ferrand-Hopital Estaing

Clermont-Ferrand, 63100, France

Location

Ap-Hp-Hopital de Bicetre

Le Kremlin-Bicêtre, 94270, France

Location

Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou

Rennes, 35000, France

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

All India Institute of Medical Sciences_New Dehli

New Dehli, New Delhi, 110029, India

Location

CMCV

Ranipet, Tamil Nadu, 632 517, India

Location

CMCV

Ranipet, Tamil Nadu, 632517, India

Location

All India Institute of Medical Sciences_New Dehli

New Delhi, 110029, India

Location

Dipartimento di Ematologia Univ. Firenze

Florence, FI, 50134, Italy

Location

Istituto Oncologico Veneto - Oncoematologia IOV

Castelfranco Veneto, 31033, Italy

Location

Oncoematologia IOV

Castelfranco Veneto, 31033, Italy

Location

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

Milan, 20124, Italy

Location

Azienda OU "S.Maria della Misericordia"

Udine, 33100, Italy

Location

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

Verona, 37126, Italy

Location

Ospedale Donna Bambino U.O.C. Oncoematologia Pediatrica

Verona, 37126, Italy

Location

Nagoya University Hospital_Blood Transfusion

Aichi, 466-8560, Japan

Location

Kagoshima City Hospital_Pediatrics

Kagoshima, 890-8760, Japan

Location

Kagoshima City Hospital

Kagoshima, 890-8760, Japan

Location

St. Marianna University School of Medicine Hospital_Pediatrics

Kanagawa, 216-8511, Japan

Location

Mie University Hospital_Dept.of Blood Trans.Med & Cell

Mie, 514-8507, Japan

Location

Nara Medical University Hospital_Pediatrics

Nara, 634-8522, Japan

Location

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

Saitama, 350-0495, Japan

Location

Ogikubo Hospital_Pediatries & Blood

Tokyo, 167-0035, Japan

Location

Hospital Pulau Pinang_Georgetown, Penang

George Town, Pulau Pinang, 10450, Malaysia

Location

Hospital Queen Elizabeth 1

Kota Kinabalu, Sabah, 88586, Malaysia

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

Rikshospitalet - avdeling for blodsykdommer

Oslo, 0027, Norway

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

SPSK nr 1 Klinika Hematoonkologii i Transplantacji Szpiku

Lublin, 20-081, Poland

Location

Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku

Lublin, 20-081, 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

Institute for Health Care of Children and Adolescents

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

Haematology Clinic

Durban, KwaZulu-Natal, 4013, South Africa

Location

Pietersburg Hospital

Polokwane, Limpopo, 0699, South Africa

Location

Daejeon Eulji Medical Center, Eulji University

Daejeon, 35233, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Universitario Regional de Málaga

Málaga, 29010, Spain

Location

Hospital Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Univ. Central de Asturias

Oviedo, 33011, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Koagulationsmottagning - SUS

Malmo, 214 28, Sweden

Location

Koagulationsmottagningen - KS

Solna, 171 64, Sweden

Location

Sunpasitthiprasong Hospital_Pediatrics Department

Ubon Ratchathani, Mueang Distirct,, 34000, Thailand

Location

Ramathibodi Hospital_Department of Haematology

Bangkok, 10400, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital _Pediatric Hematology and Oncology

Chiang Mai, 50200, Thailand

Location

İstanbul Üniversitesi İstanbul Tıp Fakültesi Hastanesi- Onkoloji Enstitüsü

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

Location

Akdeniz Üniversitesi Hastanesi- Hematoloji

Antalya, Konyaaltı/ Antalya, 01010, Turkey (Türkiye)

Location

Acıbadem Adana Hastanesi-Hematoloji

Adana, 01130, Turkey (Türkiye)

Location

Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi- Hematoloji

Adana, 01130, 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

Queen Elizabeth Hospital, Birmingham - Haemophilia

Birmingham, B15 2TH, United Kingdom

Location

Great Ormond Street Hospital for Children

London, WC1N 3HR, United Kingdom

Location

Manchester Royal Infirmary_Manchester

Manchester, M13 9WL, United Kingdom

Location

Queen's Medical Centre - Haemophilia Comprehensive Care Centre

Nottingham, NG7 2UH, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (3)

• Mahlangu J, Boban A, Bruzelius M, Castaman G, Hampton KK, Knoebl P, Lebreton A, Linari S, Lopez-Jaime FJ, Tavares CMMT, Nekkal MS, Nogami K, Nielsen ARH, Shapiro AD, D'Oiron R. Concizumab in hemophilia with inhibitors: Longer-term efficacy and safety results from the phase 3 explorer7 study. Blood Adv. 2026 Jan 7:bloodadvances.2025018264. doi: 10.1182/bloodadvances.2025018264. Online ahead of print.

  PMID: 41499759 DERIVED

• 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.

  PMID: 39099801 DERIVED

• 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.

  PMID: 37646676 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: Participants will be randomised to concizumab prophylaxis (ppx) or no ppx or assigned into non-randomised treatment arms, based on their treatment regimen before entering the trial. Main part of trial is completed when participant has completed at least 24 weeks of participation in arm 1 or 32 weeks in arms 2, 3 and 4. After main part, all participants will be offered to continue in extension part and receive treatment until concizumab is commercially available in their countries or until 31 December 2026 for up to 332 weeks (arms 1-4) or up to 324 weeks (randomised to arm 1 before the pause). After extension part, participant will enter safety follow-up part on visit 26a, which defines end-of-treatment. Participant will receive last dose of trial drug at home on day prior to visit 26a. On visit 26a, participants will either start up commercially available concizumab or revert to previous ppx schedule or on-demand regimen. Follow-up part will start on visit 26a and lasts for 7 weeks.

Study Record Dates

• First Submitted: September 6, 2019
• First Posted: September 10, 2019
• Study Start: October 21, 2019
• Primary Completion: December 27, 2021
• Study Completion (Estimated): February 21, 2027
• Last Updated: March 24, 2026
• Results First Posted: April 27, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CR (3); ES (7); PT (1); DK (1); TU (4); BU (1); AL (2); FR (4); IN (7); JP (8); ZA (3); SL (1); SE (2); RU (5); GB (5); UA (2); CA (1); NO (1); MY (4); IT (7); US (7); TH (3); PL (6); CZ (2); KR (2); AU (3); ME (1)