Clinical trial NCT04083781: Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia With Inhibitors
Official title: Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B With Inhibitors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Haemophilia A With Inhibitors
Haemophilia B With Inhibitors
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-09-10
Enrollment: 134
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
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 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.


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 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)).

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.
* 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.)

Primary outcomes:
measure: Rate of Treated Spontaneous and Traumatic Bleeding Episodes
timeFrame: 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:
measure: Rate of Treated Spontaneous Bleeding Episodes
timeFrame: 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
measure: Rate of Treated Spontaneous and Traumatic Joint Bleeds
timeFrame: 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
measure: Rate of Treated Spontaneous and Traumatic Target Joint Bleeds
timeFrame: 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
measure: Change in 36-item Short Form Health Survey (SF-36v2) Bodily Pain
timeFrame: Baseline (week 0), Week 24
measure: Change in SF36v2 Physical Functioning
timeFrame: Baseline (week 0), Week 24
measure: Number of Thromboembolic Events
timeFrame: On demand (arm 1 ): From week 0 until start of concizumab treatment (atleast 24 weeks) Concizumab (arms 2-4): From week 0 up until week 56 cut-off Extension Concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off
measure: Number of Thromboembolic Events
timeFrame: From week 0 to end of trial (week 167)
measure: Number of Hypersensitivity Type Reactions
timeFrame: On demand (arm 1 ): From week 0 until start of concizumab treatment (atleast 24 weeks) Concizumab (arms 2-4): From week 0 up until week 56 cut-off Extension Concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off
measure: Number of Hypersensitivity Type Reactions
timeFrame: From week 0 to end of trial (week 167)
measure: Number of Injection Site Reactions
timeFrame: On demand (arm 1 ): From week 0 until start of concizumab treatment (atleast 24 weeks) Concizumab (arms 2-4): From week 0 up until week 56 cut-off Extension Concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off
measure: Number of Injection Site Reactions
timeFrame: From week 0 to end of trial (week 167)
measure: Number of Participants With Antibodies to Concizumab
timeFrame: Concizumab (arms 2-4): From week 0 up until week 56 cut-off Extension Concizumab (arm 1): From start of new concizumab dosing regimen (week 25) up until week 56 cut-off
measure: Number of Participants With Antibodies to Concizumab
timeFrame: From week 0 to end of trial (week 167)
measure: Pre-dose (Trough) Concizumab Plasma Concentration (Ctrough)
timeFrame: Pre-dose (prior to concizumab administration at week 56)
measure: Pre-dose Thrombin Peak
timeFrame: Pre-dose (prior to concizumab administration at week 56)
measure: Pre-dose Free Tissue Factor Pathway Inhibitor (TFPI) Concentration
timeFrame: Pre-dose (prior to concizumab administration at week 56)
measure: Maximum Concizumab Plasma Concentration (Cmax)
timeFrame: Week 24: Predose, 3 hours (h), 6h, 9h, 24h
measure: Area Under the Concizumab Plasma Concentration-time Curve (AUC)
timeFrame: Week 24: Predose, 3 hours (h), 6h, 9h, 24h
Other outcomes:
Locations:
city: Orange
country: United States
facility: Center for Inherited Blood Dis
state: California
city: Atlanta
country: United States
facility: Children's Healthcare Atlanta
state: Georgia
city: Indianapolis
country: United States
facility: Indiana Hemophilia-Thromb Ctr
state: Indiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine_St. Louis
state: Missouri
city: Charlotte
country: United States
facility: St. Jude Affiliate Clinic at Novant Health Hemby Children's
state: North Carolina
city: Nashville
country: United States
facility: TriStar Medical Group Children's Specialist
state: Tennessee
city: San Antonio
country: United States
facility: University of Texas San Antonio
state: Texas
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: Murdoch
country: Australia
facility: Fiona Stanley Hospital - Haemophilia and Haemostasis Centre
state: Western Australia
city: Wien
country: Austria
facility: Klin. Abt. f. Hämatologie und Hämostaseologie, AKH Wien
city: Sofia
country: Bulgaria
facility: UMHAT "Tsaritsa Yoanna-ISUL"
city: Zagreb
country: Croatia
facility: KBC Zagreb, Rebro, Hemofilija centar
city: Zagreb
country: Croatia
facility: KBC Zagreb, Zavod za pedijatrijsku hematologiju
city: Praha 2
country: Czechia
facility: Ustav Hematologie a krevni tranfuze
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
city: Aarhus N
country: Denmark
facility: Skejby Blodsygdomme, blødercentret
city: Bron
country: France
facility: Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1
city: Clermont-Ferrand
country: France
facility: Centre Hospitalier de Clermont-Ferrand-Hopital Estaing
city: Le Kremlin-Bicetre
country: France
facility: Ap-Hp-Hopital de Bicetre-1
city: Rennes
country: France
facility: Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou
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: New Dehli
country: India
facility: All India Institute of Medical Sciences_New Dehli
state: New Delhi
city: Ranipet
country: India
facility: CMCV
state: Tamil Nadu
city: Ranipet
country: India
facility: CMCV
state: Tamil Nadu
city: New Delhi
country: India
facility: All India Institute of Medical Sciences_New Dehli
city: Firenze
country: Italy
facility: Dipartimento di Ematologia Univ. Firenze
state: FI
city: Castelfranco Veneto
country: Italy
facility: Oncoematologia IOV
city: Milano
country: Italy
facility: Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano
city: Udine
country: Italy
facility: Azienda OU "S.Maria della Misericordia"
city: Verona
country: Italy
facility: Ospedale Donna Bambino U.O.C. Oncoematologia Pediatrica
city: Aichi
country: Japan
facility: Nagoya University Hospital_Blood Transfusion
city: Kagoshima
country: Japan
facility: Kagoshima City Hospital
city: Kanagawa
country: Japan
facility: St. Marianna University School of Medicine Hospital_Pediatrics
city: Nara
country: Japan
facility: Nara Medical University Hospital_Pediatrics
city: Saitama
country: Japan
facility: Saitama Medical Univ. Hospital
city: Tokyo
country: Japan
facility: Ogikubo Hospital_Pediatries & Blood
city: Daejeon
country: Korea, Republic of
facility: Daejeon Eulji Medical Center, Eulji University
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Kota Kinabalu
country: Malaysia
facility: Hospital Queen Elizabeth 1
state: Sabah
city: Ampang, Selangor
country: Malaysia
facility: Hospital Ampang
city: Georgetown, Penang
country: Malaysia
facility: Hospital Pulau Pinang_Georgetown, Penang
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. José Eleuterio González
state: Nuevo León
city: Oslo
country: Norway
facility: Rikshospitalet - avdeling for blodsykdommer
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
state: Mazowieckie
city: Kraków
country: Poland
facility: Szpital Uniwersytecki, Oddzial Kliniczny Hematologii
state: Małopolskie
city: Lublin
country: Poland
facility: SPSK nr 1 Klinika Hematoonkologii i Transplantacji Szpiku
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
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: Kragujevac
country: Serbia
facility: University Clinical Centre Kragujevac
city: Bratislava
country: Slovakia
facility: Nemocnica sv. Cyrila a Metoda, UNB,Klinika hemat. a transfuz
city: Parktown, Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: Durban
country: South Africa
facility: Haematology Clinic
state: KwaZulu-Natal
city: Polokwane
country: South Africa
facility: Pietersburg Hospital
state: Limpopo
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: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Solna
country: Sweden
facility: Koagulationsmottagningen
city: Ubon Ratchathani
country: Thailand
facility: Sunpasitthiprasong Hospital
state: Mueang Distirct,
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital_Bangkok_0
city: Chiang Mai
country: Thailand
facility: Hematology and Oncology, Dept.of Pediatrics, CMU
city: Adana
country: Turkey
facility: Acibadem Adana Hastanesi
city: Adana
country: Turkey
facility: Cukurova Universitesi
city: Antalya
country: Turkey
facility: Akdeniz Universitesi
city: Capa-ISTANBUL
country: Turkey
facility: Istanbul University Oncology Institute
city: Kyiv
country: Ukraine
facility: National specialized children clinic "OHMATDYT"
city: Lviv
country: Ukraine
facility: Institute of blood pathology and transfusion medicine
city: Birmingham
country: United Kingdom
facility: West Midlands Adult Comprehensive Care Haemophilia
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
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: