Clinical trial NCT04082429: Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia Without Inhibitors
Official title: Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B Without Inhibitors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Haemophilia A Without Inhibitors
Haemophilia B Without Inhibitors
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-09-09
Enrollment: 156
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 21-Apr-26 at latest. Patients will be in ext. part for up to 257 (arms 2-4) or 265 wks (arm 1) for up to additional 128 (arms 2-4) or 136 wks (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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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%).

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.)

Primary outcomes:
measure: For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
timeFrame: 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)
measure: For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
timeFrame: 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)
Secondary outcomes:
measure: For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
timeFrame: Time frame is presented under 'outcome measure description'
measure: For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes
timeFrame: Time frame is presented under 'outcome measure description'
measure: For haemophilia A patients without inhibitors: Number of treated spontaneous bleeding episodes
timeFrame: 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)
measure: For haemophilia B patients without inhibitors: Number of treated spontaneous bleeding episodes
timeFrame: 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)
measure: For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds
timeFrame: 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)
measure: For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds
timeFrame: 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)
measure: For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds
timeFrame: 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)
measure: For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds
timeFrame: 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)
measure: Number of thromboembolic events
timeFrame: Time frame is presented under 'outcome measure description'.
measure: Number of thromboembolic events
timeFrame: 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).
measure: Number of hypersensitivity type reactions
timeFrame: Time frame is presented under 'outcome measure description'.
measure: Number of hypersensitivity type reactions
timeFrame: 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).
measure: Number of injection site reactions
timeFrame: Time frame is presented under 'outcome measure description'.
measure: Number of injection site reactions
timeFrame: 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).
measure: Number of patients with antibodies to concizumab
timeFrame: Time frame is presented under 'outcome measure description'.
measure: Number of patients with antibodies to concizumab
timeFrame: 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).
measure: Pre-dose (trough) concizumab plasma concentration (Ctrough)
timeFrame: Prior to the concizumab administration at week 24 (after restart)
measure: Pre-dose thrombin peak
timeFrame: Prior to the concizumab administration at week 24 (after restart)
measure: Pre-dose free tissue factor pathway inhibitor (TFPI) concentration
timeFrame: Prior to the concizumab administration at week 24 (after restart)
measure: Maximum concizumab plasma concentration (Cmax)
timeFrame: From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)
measure: Area under the concizumab plasma concentration-time curve (AUC)
timeFrame: From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles - Endocrinology
state: California
city: Orange
country: United States
facility: Center for Inherited Blood Disorders
state: California
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Hershey
country: United States
facility: M.S. Hershey Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center_Nashville_0
state: Tennessee
city: San Antonio
country: United States
facility: University of Texas San Antonio
state: Texas
city: Milwaukee
country: United States
facility: Versiti, CCBD
state: Wisconsin
city: Algiers
country: Algeria
facility: Haematology and Blood Bank Department
city: Constantine
country: Algeria
facility: CHU Constantine BEN BADIS/ Hematology department
city: Melbourne
country: Australia
facility: The Alfred
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital - Haemophilia and Haemostasis Centre
state: Western Australia
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of Republic Srpska (205)
city: Sofia
country: Bulgaria
facility: UMHAT "Tsaritsa Yoanna-ISUL"
city: Hamilton
country: Canada
facility: Hamltn Hth Sci/McMstr Child Hosp
state: Ontario
city: Zagreb
country: Croatia
facility: KBC Zagreb, Rebro, Hemofilija centar
city: København
country: Denmark
facility: Copenhagen Center for Heamatology
city: Tallinn
country: Estonia
facility: North Estonia Medical Centre Foundation
city: Brest
country: France
facility: Centre Hospitalier Regional Et Universitaire de Brest-Hopital de La Cavale Blanche
city: Caen
country: France
facility: CHU de Caen - Côte de Nacre
city: Le Kremlin Bicetre
country: France
facility: Hopital de Bicetre
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Homburg
country: Germany
facility: UKS - Hämostaseologie und Transfusionsmedizin
city: Budapest
country: Hungary
facility: MH Eü. Központ -Orszagos Haemophilia Kozpont
city: Bangalore
country: India
facility: St. John's Medical college and Hospital
state: Karnataka
city: Pune
country: India
facility: Sahyadri Speciality Hospital
state: Maharashtra
city: Pune
country: India
facility: Sahyadri Super Speciality Hospital
state: Maharashtra
city: Jaipur
country: India
facility: J K Lon Hospital
state: Rajasthan
city: Tel-Hashomer
country: Israel
facility: Sheba MC The Israeli National Hemophilia Center
city: Torino
country: Italy
facility: A.O.U Città Salute Scienza Torino
city: Aichi
country: Japan
facility: Nagoya University Hospital_Blood Transfusion
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital, Hematology
city: Hyogo
country: Japan
facility: Hyogo prefectural kobe children's hospital
city: Osaka
country: Japan
facility: Osaka National Hospital
city: Saitama
country: Japan
facility: Saitama Children's Med Centre_Hematology-Oncology
city: Saitama
country: Japan
facility: Saitama Medical Univ. Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Children's Hospital
city: Tokyo
country: Japan
facility: National Center for Child Health and Development_Hematology
city: Tokyo
country: Japan
facility: National Center for Child Health and Development
city: Tokyo
country: Japan
facility: Ogikubo Hospital_Pediatries & Blood
city: Daejeon
country: Korea, Republic of
facility: Daejeon Eulji University Hospital
city: Jeju-do
country: Korea, Republic of
facility: Jeju National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Vilnius
country: Lithuania
facility: Children Oncohaematology department Children's Hospital,
city: Vilnius
country: Lithuania
facility: Vilnius University hospital Santaros klinikos
city: Ampang, Selangor
country: Malaysia
facility: Hospital Ampang
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José Eleuterio González
state: Nuevo León
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
state: Mazowieckie
city: Kraków
country: Poland
facility: Szpital Uniwersytecki, Oddzial Kliniczny Hematologii
state: Małopolskie
city: Poznań
country: Poland
facility: Uniwersytecki Szpital Kliniczny W Poznaniu
state: Wielkopolskie
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku
city: Porto
country: Portugal
facility: ULS São João, E.P.E.
city: Krasnodar
country: Russian Federation
facility: Children Regional Clinical Hospital
city: Moscow
country: Russian Federation
facility: Morozovskaya municipal children hospital
city: Moscow
country: Russian Federation
facility: National Medical Research institution of haemotology
city: Petrozavodsk
country: Russian Federation
facility: Republican Hospital n.a. V. A. Baranov
city: Saint-Petersburg
country: Russian Federation
facility: City out-patient clinic 37, City Hemophilia Centre
city: Belgrade
country: Serbia
facility: Institute for Mother and Child Health Care of Serbia
city: Kragujevac
country: Serbia
facility: University Clinical Centre Kragujevac
city: Novi Sad
country: Serbia
facility: Clinical Centre of Vojvodina
city: Polokwane
country: South Africa
facility: Pietersburg Hospital
state: Limpopo
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Malmö
country: Sweden
facility: Koagulationsmottagning
city: Solna
country: Sweden
facility: Koagulationsmottagningen
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich - Klinik für Medizinische Onkologie und Hämatologie
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital_Bangkok_0
city: Ankara
country: Turkey
facility: Gazi University
state: Beşevler/Ankara
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty
city: Capa-ISTANBUL
country: Turkey
facility: Istanbul University Oncology Institute
city: Edirne
country: Turkey
facility: Trakya University
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Samsun
country: Turkey
facility: Ondokuz Mayis University Medical Faculty Ped. Haematology
city: Kyiv
country: Ukraine
facility: National specialized children clinic "OHMATDYT"
city: Lviv
country: Ukraine
facility: Institute of blood pathology and transfusion medicine
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: London
country: United Kingdom
facility: Royal Free Haemophilia Comprehensive Care Center
city: London
country: United Kingdom
facility: Royal Free Haemophilia Comprehensive Care Centre
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References: