Clinical trial NCT05135559: A Research Study on How Well Concizumab Works for You if You Have Haemophilia A or B With or Without Inhibitors
Official title: Open-label Study Investigating Efficacy, Safety and Pharmacokinetics of Concizumab Prophylaxis in Children Below 12 Years With Haemophilia A or B With or Without Inhibitors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Haemophilia A and B With and Without Inhibitors
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-11-26
Enrollment: 153
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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).

Primary outcomes:
measure: 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 episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For non-inhibitor patients treated on demand during at least the last 52 weeks prior enrolment: Number of treated spontaneous and traumatic bleeding episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
Secondary outcomes:
measure: 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)
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For inhibitor patients with at least 26 weeks on-demand treatment during the last 52 weeks prior enrolment: Number of treated joint bleeding episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: 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 joints
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For non-inhibitor patients treated on-demand during at least the last 52 weeks prior enrolment: Number of all bleeding episodes (spontaneous and traumatic)
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For non-inhibitor patients treated on-demand during at least the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For non-inhibitor patients treated on-demand at least the last 52 weeks prior enrolment: Number of treated joint bleeding episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For non-inhibitor patients treated on-demand at least the last 52 weeks prior enrolment: Number of treated bleeding episodes in baseline target joints
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: 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 episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: 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)
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated spontaneous bleeding episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: For non-inhibitor patients with at least 26 weeks PPX treatment during the last 52 weeks prior enrolment: Number of treated joint bleeding episodes
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: 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 joints
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: Concizumab-naïve pateints - Number of treatment emergent adverse events, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: Number of thromboembolic events, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: Number of hypersensitivity type reactions, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: Number of injection site reactions, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: Number of patients who develop antibodies to concizumab - yes/no, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: Number of treatment emergent adverse events, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: From start of treatment (week 0) up until the primary analysis cut-off (at least 32 weeks)
measure: Concizumab plasma concentrations prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: Week 32
measure: Peak thrombin generation prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: Week 32
measure: Free TFPI concentration prior to dosing, reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: Week 32
measure: Pre-dose (trough) concizumab plasma concentration (Ctrough), reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: Prior to the concizumab administration at week 20
measure: Maximum concizumab plasma concentration (Cmax), reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: From 0 to 24 hours where 0 is the time of the concizumab dose at week 20
measure: Area under the concizumab plasma concentration-time curve (AUC), reported both separately for inhibitor and non-inhibitor patients and combined
timeFrame: From 0 to 24 hours where 0 is the time of the concizumab dose at week 20
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Childrens Hosp San Diego
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Orlando
country: United States
facility: Arnold Palmer Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Nemours Child Orlando Hem/Onc.
state: Florida
city: Augusta
country: United States
facility: Augusta Univ/Childrens Hosp-GA
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Childrens Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia-Thromb Ctr
state: Indiana
city: New Orleans
country: United States
facility: Children's Hosp-New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Omaha
country: United States
facility: Children's Nebraska
state: Nebraska
city: Greenville
country: United States
facility: ECU Sickle Cell Comp Clinic
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: St Christopher Hosp for Child
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Hemostasis Treatment Clinic
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Hospital-Hematology-Oncology
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital_Houston
state: Texas
city: Charlottesville
country: United States
facility: Pediatrics Hematology/Oncology Clinic Battle Building
state: Virginia
city: Algiers
country: Algeria
facility: Haematology and Blood Bank Department
city: Constantine
country: Algeria
facility: CHU Constantine BEN BADIS/ Hematology department
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of Republic Srpska (545)
city: Tuzla
country: Bosnia and Herzegovina
facility: University Clinical Centre Tuzla
city: Plovdiv
country: Bulgaria
facility: UMHAT "Sveti Georgi" Clinica of Pediatric
city: Sofia
country: Bulgaria
facility: UMHAT "Tsaritsa Yoanna-ISUL"
city: Varna
country: Bulgaria
facility: UMHAT "Sveta Marina" EAD
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital
state: Ontario
city: Tallinn
country: Estonia
facility: Tallinn Children's Hospital
city: Chambery
country: France
facility: Centre Hospitalier Metropole Savoie
city: Le Kremlin Bicetre Cedex
country: France
facility: Ap-Hp-Hopital de Bicetre-1
city: Paris
country: France
facility: Ap-Hp-Hopital Necker-1
city: Athens
country: Greece
facility: Aghia Sophia Childrens' Hospital
city: Thessaloniki
country: Greece
facility: 'Ippokrateio' General Hospital of Thessaloniki
city: Thessaloniki
country: Greece
facility: 'Ippokrateio' General Hospital of Thessaloniki
city: Guwahati
country: India
facility: Guwahati Medical College
state: Assam
city: Guwahati
country: India
facility: Guwahati Medical College
state: Assam
city: Surat
country: India
facility: Nirmal Hospital Pvt. Ltd.
state: Gujarat
city: Kolhapur
country: India
facility: SSSH_Dept. of Clinical Haematology & Haemato Oncology
state: Maharashtra
city: Mumbai
country: India
facility: Seth GS Medical College & KEM Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Seth GS Medical College & KEM Hospital
state: Maharashtra
city: Mumbai
country: India
facility: K.J Somaiya Hospital and Research Centre
state: Maharashtra
city: Mumbai
country: India
facility: K.J Somaiya Hospital and Research Centre
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Super Speciality Hospital
state: Maharashtra
city: Mumbai
country: India
facility: MCGM - Comprehensive Thalassemia Care
state: Maharastra
city: Mumbai
country: India
facility: MCGM - Comprehensive Thalassemia Care
state: Maharastra
city: Cuttack
country: India
facility: S.C.B. Medical College
state: Orissa
city: Jaipur
country: India
facility: J K Lon Hospital
state: Rajasthan
city: Noida
country: India
facility: Post Graduate Institute of Child Health
state: Uttar Pradesh
city: Lucknow
country: India
facility: SGPGI
state: Uttart Pradesh
city: Catania
country: Italy
facility: A.O.U policlinico "G. Rodolico-San Marco"
city: Firenze
country: Italy
facility: Dipartimento di Ematologia Univ. Firenze
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Parma
country: Italy
facility: Azienda Ospedaliera-Universitaria Parma
city: Kanagawa
country: Japan
facility: St. Marianna University School of Medicine Hospital_Pediatrics
city: Saitama
country: Japan
facility: Saitama Children's Med Centre_Hematology-Oncology
city: Saitama
country: Japan
facility: Saitama Children's Med Centre_Hematology-Oncology
city: Beirut
country: Lebanon
facility: Saint George Hospital University Medical Center
city: Beirut
country: Lebanon
facility: Saint George Hospital University Medical Center
city: Tripoli
country: Lebanon
facility: Hospital Nini
city: Vilnius
country: Lithuania
facility: Centre of Oncology and Hematology, Vilnius University
city: Kampung Baru
country: Malaysia
facility: Hospital Tunku Azizah
state: Kuala Lumpur
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
state: Penang
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
state: Sarawak
city: Kuala Terengganu
country: Malaysia
facility: Hospital Sultanah Nur Zahirah
state: Terengganu
city: Skopje
country: North Macedonia
facility: PHI University Clinic for Children's Diseases Skopje
city: Oslo
country: Norway
facility: Klinisk forskningspost
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. J.Mikulicza-Radeckiego
state: Dolnoslaskie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Dzieciecy, Dzial Krwiolecznictwa
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne WUM
city: Warszawa
country: Poland
facility: Uniwersyteckie Centrum Kliniczne WUM
city: Bucharest
country: Romania
facility: Clinic of Haematology, Fundeni Clinical Institute
city: Cluj-Napoca
country: Romania
facility: Spitalul Clinic de Urgenta pentru Copii Cluj Napoca
city: Oradea
country: Romania
facility: Spitalul Clinic Judetean De Urgenta Bihor
city: Oradea
country: Romania
facility: Spitalul Clinic Judetean De Urgenta Bihor
city: Krasnodar
country: Russian Federation
facility: Children Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Morozovskaya municipal children hospital
city: Saint-Petersburg
country: Russian Federation
facility: City out-patient clinic 37, City Hemophilia Centre
city: Parktown, Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: El Palmar
country: Spain
facility: Hospital Virgen de la Arrixaca - Hematología
state: Murcia
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Göteborg
country: Sweden
facility: Koagulationscentrum
city: Ubon Ratchathani
country: Thailand
facility: Sunpasitthiprasong Hospital
state: Mueang Distirct,
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital_Bangkok_0
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital - Hematology and Oncology
city: Ankara
country: Turkey
facility: Gazi University
state: Beşevler/Ankara
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Samsun
country: Turkey
facility: Ondokuz Mayis University Medical Faculty Ped. Haematology
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol & Weston NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol & Weston NHS Foundation Trust
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 2834)
role: STUDY_DIRECTOR
References: