MedPath

A Research Study on How Well Concizumab Works for You if You Have Haemophilia A or B With or Without Inhibitors

Phase 3
Recruiting
Conditions
Haemophilia A and B With and Without Inhibitors
Interventions
Registration Number
NCT05135559
Lead Sponsor
Novo Nordisk A/S
Brief Summary

This study will test how well a new medicine called concizumab works for participants who have haemophilia A or B with or without inhibitors. The purpose is to show that concizumab can prevent bleeds and is safe to use.

Participants will have to inject the study medicine every day under the skin with a pen-injector.

The study will last for at least 2 years and up to about 4 years. The length of time the participant will be in the study depends on if the study medicine will be available for purchase in their country.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
Inclusion Criteria
  • Informed consent/assent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.

  • Diagnosis of congenital severe haemophilia A (FVIII below 1%) or moderate/severe congenital haemophilia B (FIX (coagulation factor IX) below or equal to 2%), or congenital haemophilia with inhibitors.

  • For arm 1 only: Male aged below 12 years of age at the time of signing informed consent.

  • For arm 1 only: Patients with inhibitors (haemophilia A with inhibitors or haemophilia B with inhibitors)

    1. Patients with HAwI (haemophilia A with inhibitors) with historical medical records of a total of at least 26 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia <1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available).
    2. Patients with HBwI (haemophilia B with inhibitors) with historical medical records of a total of at least 26 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia <1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available).
    3. Patients with HBwI regardless of the regimen and duration of previous haemophilia treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products)
  • For arm 1 only: Patients without inhibitors (haemophilia A or haemophilia B)

    1. Patients with historical medical records of at least 52 weeks of on-demand treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products; Surgery related PPX or short-term PPX (e.g., in relation to a severe bleed) is not allowed) during the last year prior to enrolment and with at least 3 documented treated bleeds (For participants less than (<) 2 years of age there is no limitation for number of documented treated bleeds in the medical history) during this period
    2. Patients with historical medical records of a total of at least 26 weeks of PPX (prophylaxis) treatment (On-demand or PPX treatment qualifying for this study is understood as patient-treatment solely for bleeds with intravenous coagulation factor-containing products) within the last 52 weeks prior to enrolment (For patients below 1 year of age that have been diagnosed with haemophilia <1 year prior to enrolment, historical medical records from time of diagnosis will suffice as long as medical records of a total of at least 26 weeks of relevant treatment is available)
  • For arm 2 only: Male patients (regardless of age) previously treated with concizumab via compassionate use.

Exclusion Criteria
  • Known or suspected hypersensitivity to study intervention or related products.
  • Known inherited or acquired coagulation disorder other than congenital haemophilia.
  • Ongoing or planned Immune Tolerance Induction treatment.
  • History of thromboembolic disease (aIncludes 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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Patients coming from compassionate useConcizumabPatients previously treated with concizumab via compassionate use, either on an individual patient basis or through the concizumab compassionate use programme NN7415-4807
Concizumab-naïve patientsConcizumabConcizumab-naïve participants below 12 years of age at the time of consent/assent
Primary Outcome Measures
NameTimeMethod
For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients treated on demand during at least the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

Secondary Outcome Measures
NameTimeMethod
For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic)From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target jointsFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated joint bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients treated on-demand during at least the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic)From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients treated on-demand during at least the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients treated on-demand at least the last 52 weeks prior enrolment: Number of treated joint bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients treated on-demand at least the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target jointsFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic)From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated joint bleeding episodesFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target jointsFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of episode(s)

Concizumab-naïve pateints - Number of treatment emergent adverse events, reported both separately for inhibitor and non-inhibitor patients and combinedFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of event(s)

Number of thromboembolic events, reported both separately for inhibitor and non-inhibitor patients and combinedFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of event(s)

Number of hypersensitivity type reactions, reported both separately for inhibitor and non-inhibitor patients and combinedFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of event(s)

Number of injection site reactions, reported both separately for inhibitor and non-inhibitor patients and combinedFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of event(s)

Number of patients who develop antibodies to concizumab - yes/no, reported both separately for inhibitor and non-inhibitor patients and combinedFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of patient(s)

Number of treatment emergent adverse events, reported both separately for inhibitor and non-inhibitor patients and combinedFrom start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)

Count of event(s)

Concizumab plasma concentrations prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combinedWeek 32

Measured in ng/mL

Peak thrombin generation prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combinedWeek 32

Measured in nM

Free TFPI concentration prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combinedWeek 32

Measured in ng/mL

Pre-dose (trough) concizumab plasma concentration (Ctrough), reported both separately for inhibitor and non-inhibitor patients and combinedPrior to the concizumab administration at week 20

Measured in ng/mL

Maximum concizumab plasma concentration (Cmax), reported both separately for inhibitor and non-inhibitor patients and combinedFrom 0 to 24 hours where 0 is the time of the concizumab dose at week 20

Measured in ng/mL

Area under the concizumab plasma concentration-time curve (AUC), reported both separately for inhibitor and non-inhibitor patients and combinedFrom 0 to 24 hours where 0 is the time of the concizumab dose at week 20

Measured in ng\*hr/mL

Trial Locations

Locations (88)

Spitalul Clinic Judetean De Urgenta Bihor

🇷🇴

Oradea, Romania

Children Regional Clinical Hospital

🇷🇺

Krasnodar, Russian Federation

Morozovskaya municipal children hospital

🇷🇺

Moscow, Russian Federation

Hospital Vall d'Hebron

🇪🇸

Barcelona, Spain

Siriraj Hospital - Hematology and Oncology

🇹🇭

Bangkok, Thailand

Saitama Children's Med Centre_Hematology-Oncology

🇯🇵

Saitama, Japan

Klinisk forskningspost

🇳🇴

Oslo, Norway

Uniwersyteckie Centrum Kliniczne WUM

🇵🇱

Warszawa, Poland

Clinic of Haematology, Fundeni Clinical Institute

🇷🇴

Bucharest, Romania

Spitalul Clinic de Urgenta pentru Copii Cluj Napoca

🇷🇴

Cluj-Napoca, Romania

Haematology and Blood Bank Department

🇩🇿

Algiers, Algeria

CHU Constantine BEN BADIS/ Hematology department

🇩🇿

Constantine, Algeria

UMHAT "Tsaritsa Yoanna-ISUL"

🇧🇬

Sofia, Bulgaria

UMHAT "Sveta Marina" EAD

🇧🇬

Varna, Bulgaria

Azienda Ospedaliera-Universitaria Parma

🇮🇹

Parma, Italy

St. Marianna University School of Medicine Hospital_Pediatrics

🇯🇵

Kanagawa, Japan

King Chulalongkorn Memorial Hospital_Bangkok_0

🇹🇭

Bangkok, Thailand

Indiana Hemophilia-Thromb Ctr

🇺🇸

Indianapolis, Indiana, United States

Childrens Hospital of Chicago

🇺🇸

Chicago, Illinois, United States

University of Colorado Hospital

🇺🇸

Aurora, Colorado, United States

Ochsner Clinic Foundation

🇺🇸

New Orleans, Louisiana, United States

Texas Children's Hospital_Houston

🇺🇸

Houston, Texas, United States

SSSH_Dept. of Clinical Haematology & Haemato Oncology

🇮🇳

Kolhapur, Maharashtra, India

Rady Childrens Hosp San Diego

🇺🇸

San Diego, California, United States

Arnold Palmer Children's Hospital

🇺🇸

Orlando, Florida, United States

Nemours Child Orlando Hem/Onc.

🇺🇸

Orlando, Florida, United States

Augusta Univ/Childrens Hosp-GA

🇺🇸

Augusta, Georgia, United States

Memorial Health University Medical Center

🇺🇸

Savannah, Georgia, United States

Children's Hosp-New Orleans

🇺🇸

New Orleans, Louisiana, United States

The Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

Children's Nebraska

🇺🇸

Omaha, Nebraska, United States

ECU Sickle Cell Comp Clinic

🇺🇸

Greenville, North Carolina, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

St Christopher Hosp for Child

🇺🇸

Philadelphia, Pennsylvania, United States

Vanderbilt Hemostasis Treatment Clinic

🇺🇸

Nashville, Tennessee, United States

Cook Children's Hospital-Hematology-Oncology

🇺🇸

Fort Worth, Texas, United States

Pediatrics Hematology/Oncology Clinic Battle Building

🇺🇸

Charlottesville, Virginia, United States

University Clinical Center of Republic Srpska (545)

🇧🇦

Banja Luka, Bosnia and Herzegovina

University Clinical Centre Tuzla

🇧🇦

Tuzla, Bosnia and Herzegovina

UMHAT "Sveti Georgi" Clinica of Pediatric

🇧🇬

Plovdiv, Bulgaria

BC Children's Hospital

🇨🇦

Vancouver, British Columbia, Canada

McMaster Children's Hospital

🇨🇦

Hamilton, Ontario, Canada

Tallinn Children's Hospital

🇪🇪

Tallinn, Estonia

Centre Hospitalier Metropole Savoie

🇫🇷

Chambery, France

Ap-Hp-Hopital de Bicetre-1

🇫🇷

Le Kremlin Bicetre Cedex, France

Ap-Hp-Hopital Necker-1

🇫🇷

Paris, France

Aghia Sophia Childrens' Hospital

🇬🇷

Athens, Greece

'Ippokrateio' General Hospital of Thessaloniki

🇬🇷

Thessaloniki, Greece

Guwahati Medical College

🇮🇳

Guwahati, Assam, India

Nirmal Hospital Pvt. Ltd.

🇮🇳

Surat, Gujarat, India

Seth GS Medical College & KEM Hospital

🇮🇳

Mumbai, Maharashtra, India

K.J Somaiya Hospital and Research Centre

🇮🇳

Mumbai, Maharashtra, India

Sahyadri Super Speciality Hospital

🇮🇳

Pune, Maharashtra, India

MCGM - Comprehensive Thalassemia Care

🇮🇳

Mumbai, Maharastra, India

S.C.B. Medical College

🇮🇳

Cuttack, Orissa, India

J K Lon Hospital

🇮🇳

Jaipur, Rajasthan, India

Post Graduate Institute of Child Health

🇮🇳

Noida, Uttar Pradesh, India

SGPGI

🇮🇳

Lucknow, Uttart Pradesh, India

A.O.U policlinico "G. Rodolico-San Marco"

🇮🇹

Catania, Italy

Dipartimento di Ematologia Univ. Firenze

🇮🇹

Firenze, Italy

Azienda Ospedaliera di Padova

🇮🇹

Padova, Italy

Saint George Hospital University Medical Center

🇱🇧

Beirut, Lebanon

Hospital Nini

🇱🇧

Tripoli, Lebanon

Centre of Oncology and Hematology, Vilnius University

🇱🇹

Vilnius, Lithuania

Hospital Tunku Azizah

🇲🇾

Kampung Baru, Kuala Lumpur, Malaysia

Hospital Pulau Pinang

🇲🇾

George Town, Penang, Malaysia

Sarawak General Hospital

🇲🇾

Kuching, Sarawak, Malaysia

Hospital Sultanah Nur Zahirah

🇲🇾

Kuala Terengganu, Terengganu, Malaysia

PHI University Clinic for Children's Diseases Skopje

🇲🇰

Skopje, North Macedonia

Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego

🇵🇱

Wroclaw, Dolnoslaskie, Poland

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gdansk, Poland

Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa

🇵🇱

Lublin, Poland

City out-patient clinic 37, City Hemophilia Centre

🇷🇺

Saint-Petersburg, Russian Federation

Charlotte Maxeke Johannesburg Academic Hospital

🇿🇦

Parktown, Johannesburg, Gauteng, South Africa

Hospital Virgen de la Arrixaca - Hematología

🇪🇸

El Palmar, Murcia, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Hospital Universitario Regional de Málaga

🇪🇸

Málaga, Spain

Koagulationscentrum

🇸🇪

Göteborg, Sweden

Sunpasitthiprasong Hospital

🇹🇭

Ubon Ratchathani, Mueang Distirct,, Thailand

Ramathibodi Hospital

🇹🇭

Bangkok, Thailand

Gazi University

🇹🇷

Ankara, Beşevler/Ankara, Turkey

Acibadem Adana Hastanesi

🇹🇷

Adana, Turkey

Ege Universitesi Tip Fakultesi

🇹🇷

Izmir, Turkey

Ondokuz Mayis University Medical Faculty Ped. Haematology

🇹🇷

Samsun, Turkey

Birmingham Children's Hospital

🇬🇧

Birmingham, United Kingdom

University Hospitals Bristol & Weston NHS Foundation Trust

🇬🇧

Bristol, United Kingdom

Evelina London Children's Hospital

🇬🇧

London, United Kingdom

Great Ormond Street Hospital for Children

🇬🇧

London, United Kingdom

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