Research Study to Look at How Well the Drug Concizumab Works in Your Body if You Have Haemophilia With Inhibitors
- Conditions
- Haemophilia A With InhibitorsHaemophilia B With Inhibitors
- Interventions
- Registration Number
- NCT04083781
- Lead Sponsor
- Novo Nordisk A/S
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 134
- 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)).
- 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.)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: No prophylaxis Concizumab 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. Arm 2: Concizumab prophylaxis Concizumab HAwI and HBwI patients, previously treated on-demand, will be randomised 1:2 to no prophylaxis versus concizumab prophylaxis. Arm 3: Concizumab prophylaxis Concizumab 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. Arm 4: Concizumab prophylaxis Concizumab 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).
- Primary Outcome Measures
Name Time Method Rate of Treated Spontaneous and Traumatic Bleeding Episodes 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) 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.
- Secondary Outcome Measures
Name Time Method 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 bleeding episodes is presented. The observation period used for reporting this endpoint is 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 ABR. Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.
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 joint bleeds is presented. Observation period used for reporting this endpoint is OTwoATexIR. It is defined as 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 ABR. Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.
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 Rate of treated spontaneous and traumatic target joint bleeds is presented. Observation period used for reporting the endpoint is OTwoATexIR. It is defined as 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 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 terms of ABR. Week 0 is defined as time of randomisation to on-demand administration or time of start of the new concizumab dosing regimen.
Change in 36-item Short Form Health Survey (SF-36v2) Bodily Pain Baseline (week 0), Week 24 Change in 36-item SF-36v2 bodily pain from baseline (week 0) to week 24 is presented. SF-36 v2 Health Survey is 36-item generic patient-reported outcome (PRO) instrument measuring health-related quality of life and general health status across disease areas. SF-36 v2 scores are norm-based scores, i.e. transformed to a scale where the 2009 US general population has a mean of 50 and an SD of 10. Lowest and highest scores for bodily pain are 21.68 to 62.0. Higher values indicate better functional health and well-being. Observation period for reporting the data is on-treatment without data on initial regimen (OTexIR) which is defined as time period where participants are considered affected by on demand treatment or treatment with new concizumab dosing regimen. Week 0 is defined as time of randomisation to on-demand administration or start of new concizumab dosing regimen.
Change in SF36v2 Physical Functioning Baseline (week 0), Week 24 Change in 36-item SF-36v2 physical functioning from baseline (week 0) to week 24 is presented. SF-36 v2 Health Survey is 36-item generic PRO instrument measuring health-related quality of life and general health status across disease areas. SF-36 v2 scores are norm-based scores, i.e. transformed to a scale where the 2009 US general population has a mean of 50 and an SD of 10. Lowest and highest scores for physical functioning are 19.26 to 57.54. Higher values indicate better functional health and well-being. Observation period used for reporting the data is OTexIR which is defined as time period where participants are considered affected by on demand treatment or treatment with new concizumab dosing regimen. Week 0 is defined as time of randomisation to on-demand administration or start of new concizumab dosing regimen.
Number of Thromboembolic Events From week 0 to end of trial (week 167) Number of thromboembolic events is presented. The observation period used for reporting the endpoint is on-treatment period which is defined as the time period where participants are considered to be affected by on-demand treatment or concizumab treatment.
Number of Hypersensitivity Type Reactions From week 0 to end of trial (week 167) Number of hypersensitivity type reactions is presented. The observation period used for reporting the endpoint is on-treatment period which is defined as the time period where participants are considered to be affected by on-demand treatment or concizumab treatment.
Number of Injection Site Reactions From week 0 to end of trial (week 167) Number of injection site reactions is presented. The observation period used for reporting the endpoint is on-treatment period which is defined as the time period where participants are considered to be affected by on-demand treatment or concizumab treatment.
Number of Participants With Antibodies to Concizumab From week 0 to end of trial (week 167) Number of participants with antibodies to concizumab is presented. The observation period used for reporting the endpoint is on-treatment period which is defined as the time period where participants are considered to be affected by on-demand treatment or concizumab treatment.
Pre-dose (Trough) Concizumab Plasma Concentration (Ctrough) Pre-dose (prior to concizumab administration at week 56) Pre-dose (trough) concizumab plasma concentration is presented. The observation period used for reporting the endpoint is OTexIR. It is defined as the time period where participants are considered to be affected by on demand treatment or treatment with the new concizumab dosing regimen.
Pre-dose Thrombin Peak Pre-dose (prior to concizumab administration at week 56) Pre-dose thrombin peak for concizumab is presented. The observation period used for reporting the endpoint is OTexIR. It is defined as the time period where participants are considered to be affected by on demand treatment or treatment with the new concizumab dosing regimen.
Pre-dose Free Tissue Factor Pathway Inhibitor (TFPI) Concentration Pre-dose (prior to concizumab administration at week 56) Pre-dose free TFPI concentration for concizumab is presented. The observation period used for reporting the endpoint is OTexIR. It is defined as the time period where participants are considered to be affected by on demand treatment or treatment with the new concizumab dosing regimen.
Maximum Concizumab Plasma Concentration (Cmax) Week 24: Predose, 3 hours (h), 6h, 9h, 24h Maximum concizumab plasma concentration is presented. The observation period used for reporting the endpoint is on OTexIR. It is defined as the time period where participants are considered to be affected by on demand treatment or treatment with the new concizumab dosing regimen.
Area Under the Concizumab Plasma Concentration-time Curve (AUC) Week 24: Predose, 3 hours (h), 6h, 9h, 24h Area under the concizumab plasma concentration-time curve is presented. The observation period used for reporting the endpoint is OTexIR. It is defined as the time period where participants are considered to be affected by on demand treatment or treatment with the new concizumab dosing regimen.
Trial Locations
- Locations (80)
University Clinical Centre Kragujevac
🇷🇸Kragujevac, Serbia
Center for Inherited Blood Dis
🇺🇸Orange, California, United States
Children's Healthcare Atlanta
🇺🇸Atlanta, Georgia, United States
Indiana Hemophilia-Thromb Ctr
🇺🇸Indianapolis, Indiana, United States
Washington University School of Medicine_St. Louis
🇺🇸Saint Louis, Missouri, United States
St. Jude Affiliate Clinic at Novant Health Hemby Children's
🇺🇸Charlotte, North Carolina, United States
TriStar Medical Group Children's Specialist
🇺🇸Nashville, Tennessee, United States
University of Texas San Antonio
🇺🇸San Antonio, Texas, United States
Haematology and Blood Bank Department
🇩🇿Algiers, Algeria
CHU Constantine BEN BADIS/ Hematology department
🇩🇿Constantine, Algeria
The Alfred
🇦🇺Melbourne, Victoria, Australia
Fiona Stanley Hospital - Haemophilia and Haemostasis Centre
🇦🇺Murdoch, Western Australia, Australia
Klin. Abt. f. Hämatologie und Hämostaseologie, AKH Wien
🇦🇹Wien, Austria
UMHAT "Tsaritsa Yoanna-ISUL"
🇧🇬Sofia, Bulgaria
KBC Zagreb, Rebro, Hemofilija centar
🇭🇷Zagreb, Croatia
KBC Zagreb, Zavod za pedijatrijsku hematologiju
🇭🇷Zagreb, Croatia
Ustav Hematologie a krevni tranfuze
🇨🇿Praha 2, Czechia
Fakultni nemocnice v Motole
🇨🇿Praha, Czechia
Skejby Blodsygdomme, blødercentret
🇩🇰Aarhus N, Denmark
Hospices Civils de Lyon-Hopital Cardiologique Louis Pradel-1
🇫🇷Bron, France
Centre Hospitalier de Clermont-Ferrand-Hopital Estaing
🇫🇷Clermont-Ferrand, France
Ap-Hp-Hopital de Bicetre-1
🇫🇷Le Kremlin-Bicetre, France
Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou
🇫🇷Rennes, France
St. John's Medical college and Hospital
🇮🇳Bangalore, Karnataka, India
Sahyadri Speciality Hospital
🇮🇳Pune, Maharashtra, India
Sahyadri Super Speciality Hospital
🇮🇳Pune, Maharashtra, India
All India Institute of Medical Sciences_New Dehli
🇮🇳New Delhi, India
CMCV
🇮🇳Ranipet, Tamil Nadu, India
Dipartimento di Ematologia Univ. Firenze
🇮🇹Firenze, FI, Italy
Oncoematologia IOV
🇮🇹Castelfranco Veneto, Italy
Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano
🇮🇹Milano, Italy
Azienda OU "S.Maria della Misericordia"
🇮🇹Udine, Italy
Ospedale Donna Bambino U.O.C. Oncoematologia Pediatrica
🇮🇹Verona, Italy
Nagoya University Hospital_Blood Transfusion
🇯🇵Aichi, Japan
Kagoshima City Hospital
🇯🇵Kagoshima, Japan
St. Marianna University School of Medicine Hospital_Pediatrics
🇯🇵Kanagawa, Japan
Nara Medical University Hospital_Pediatrics
🇯🇵Nara, Japan
Saitama Medical Univ. Hospital
🇯🇵Saitama, Japan
Ogikubo Hospital_Pediatries & Blood
🇯🇵Tokyo, Japan
Daejeon Eulji Medical Center, Eulji University
🇰🇷Daejeon, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Hospital Queen Elizabeth 1
🇲🇾Kota Kinabalu, Sabah, Malaysia
Hospital Ampang
🇲🇾Ampang, Selangor, Malaysia
Hospital Pulau Pinang_Georgetown, Penang
🇲🇾Georgetown, Penang, Malaysia
Hospital Universitario Dr. José Eleuterio González
🇲🇽Monterrey, Nuevo León, Mexico
Rikshospitalet - avdeling for blodsykdommer
🇳🇴Oslo, Norway
Instytut Hematologii i Transfuzjologii
🇵🇱Warszawa, Mazowieckie, Poland
Szpital Uniwersytecki, Oddzial Kliniczny Hematologii
🇵🇱Kraków, Małopolskie, Poland
SPSK nr 1 Klinika Hematoonkologii i Transplantacji Szpiku
🇵🇱Lublin, Poland
Uniwersytecki Szpital Kliniczny nr 1 Klinika Hematoonkologii i Transplantacji Szpiku
🇵🇱Lublin, Poland
Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
🇵🇱Wroclaw, Poland
ULS São João, E.P.E.
🇵🇹Porto, Portugal
Children Regional Clinical Hospital
🇷🇺Krasnodar, Russian Federation
Morozovskaya municipal children hospital
🇷🇺Moscow, Russian Federation
National Medical Research institution of haemotology
🇷🇺Moscow, Russian Federation
Republican Hospital n.a. V. A. Baranov
🇷🇺Petrozavodsk, Russian Federation
City out-patient clinic 37, City Hemophilia Centre
🇷🇺Saint-Petersburg, Russian Federation
Nemocnica sv. Cyrila a Metoda, UNB,Klinika hemat. a transfuz
🇸🇰Bratislava, Slovakia
Charlotte Maxeke Johannesburg Academic Hospital
🇿🇦Parktown, Johannesburg, Gauteng, South Africa
Haematology Clinic
🇿🇦Durban, KwaZulu-Natal, South Africa
Pietersburg Hospital
🇿🇦Polokwane, Limpopo, South Africa
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
Hospital Universitario Regional de Málaga
🇪🇸Málaga, Spain
Hospital Central de Asturias
🇪🇸Oviedo, Spain
Hospital Virgen del Rocío
🇪🇸Sevilla, Spain
Koagulationsmottagningen
🇸🇪Solna, Sweden
Sunpasitthiprasong Hospital
🇹🇭Ubon Ratchathani, Mueang Distirct,, Thailand
Ramathibodi Hospital_Bangkok_0
🇹🇭Bangkok, Thailand
Hematology and Oncology, Dept.of Pediatrics, CMU
🇹🇭Chiang Mai, Thailand
Acibadem Adana Hastanesi
🇹🇷Adana, Turkey
Cukurova Universitesi
🇹🇷Adana, Turkey
Akdeniz Universitesi
🇹🇷Antalya, Turkey
Istanbul University Oncology Institute
🇹🇷Capa-ISTANBUL, Turkey
National specialized children clinic "OHMATDYT"
🇺🇦Kyiv, Ukraine
Institute of blood pathology and transfusion medicine
🇺🇦Lviv, Ukraine
West Midlands Adult Comprehensive Care Haemophilia
🇬🇧Birmingham, United Kingdom
Great Ormond Street Hospital for Children
🇬🇧London, United Kingdom
Royal Hallamshire Hospital
🇬🇧Sheffield, United Kingdom