Haemophilia A Without Inhibitors Clinical Trial
— explorer8Official title:
Efficacy and Safety of Concizumab Prophylaxis in Patients With Haemophilia A or B Without Inhibitors
| Verified date | April 2024 |
| Source | Novo Nordisk A/S |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 158 |
| Est. completion date | June 9, 2026 |
| Est. primary completion date | July 12, 2022 |
| Accepts healthy volunteers | No |
| Gender | Male |
| Age group | 12 Years and older |
| Eligibility | 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.) |
| Country | Name | City | State |
|---|---|---|---|
| Algeria | Haematology and Blood Bank Department | Algiers | |
| Algeria | CHU Constantine BEN BADIS/ Hematology department | Constantine | |
| Australia | The Alfred | Melbourne | Victoria |
| Australia | Fiona Stanley Hospital - Haemophilia and Haemostasis Centre | Murdoch | Western Australia |
| Australia | Royal Children's Hospital | Parkville | Victoria |
| Bosnia and Herzegovina | University Clinical Center of Republic Srpska (205) | Banja Luka | |
| Bulgaria | UMHAT "Tsaritsa Yoanna-ISUL" | Sofia | |
| Canada | Hamltn Hth Sci/McMstr Child Hosp | Hamilton | Ontario |
| Croatia | KBC Zagreb, Rebro, Hemofilija centar | Zagreb | |
| Denmark | Copenhagen Center for Heamatology | København | |
| Estonia | North Estonia Medical Centre Foundation | Tallinn | |
| France | Centre Hospitalier Regional Et Universitaire de Brest-Hopital Morvan | Brest | |
| France | CHU de Caen - Côte de Nacre | Caen | |
| France | Hopital de Bicetre | Le Kremlin Bicetre | |
| France | Hôpital Pontchaillou | Rennes | |
| Germany | UKS - Hämostaseologie und Transfusionsmedizin | Homburg | |
| Hungary | MH Eü. Központ -Orszagos Haemophilia Kozpont | Budapest | |
| India | St. John's Medical college and Hospital | Bangalore | Karnataka |
| India | J K Lon Hospital | Jaipur | Rajasthan |
| India | Sahyadri Speciality Hospital | Pune | Maharashtra |
| India | Sahyadri Super Speciality Hospital | Pune | Maharashtra |
| Israel | Sheba MC The Israeli National Hemophilia Center | Tel-Hashomer | |
| Italy | A.O.U Città Salute Scienza Torino | Torino | |
| Japan | Nagoya University Hospital_Blood Transfusion | Aichi | |
| Japan | Hiroshima University Hospital, Hematology | Hiroshima | |
| Japan | Hyogo prefectural kobe children's hospital | Hyogo | |
| Japan | Osaka National Hospital | Osaka | |
| Japan | Saitama Children's Med Centre_Hematology-Oncology | Saitama | |
| Japan | Saitama Medical Univ. Hospital | Saitama | |
| Japan | Shizuoka Children's Hospital | Shizuoka | |
| Japan | National Center for Child Health and Development | Tokyo | |
| Japan | National Center for Child Health and Development_Hematology | Tokyo | |
| Japan | Ogikubo Hospital_Pediatries & Blood | Tokyo | |
| Korea, Republic of | Daejeon Eulji University Hospital | Daejeon | |
| Korea, Republic of | Jeju National University Hospital | Jeju-do | |
| Korea, Republic of | Severance Hospital, Yonsei University Health System | Seoul | |
| Lithuania | Children Oncohaematology department Children's Hospital, | Vilnius | |
| Lithuania | Vilnius University hospital Santaros klinikos | Vilnius | |
| Malaysia | Hospital Ampang | Ampang, Selangor | |
| Mexico | Hospital Universitario Dr. José Eleuterio González | Monterrey | Nuevo León |
| Poland | Szpital Uniwersytecki, Oddzial Kliniczny Hematologii | Kraków | Malopolskie |
| Poland | SPSK nr 1 Klinika Hematoonkologii i Transplantacji Szpiku | Lublin | |
| Poland | Uniwersytecki Szpital Kliniczny W Poznaniu | Poznan | Wielkopolskie |
| Poland | Intytut Hematologii i Transfuzjologii | Warszawa | Mazowieckie |
| Portugal | Centro Hospitalar de São João_Porto | Porto | |
| Russian Federation | 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 | |
| Serbia | Institute for Mother and Child Health Care of Serbia | Belgrade | |
| Serbia | University Clinical Centre Kragujevac | Kragujevac | |
| Serbia | Clinical Centre of Vojvodina, Haematology Clinic | Novi Sad | |
| Slovakia | Nemocnica sv. Cyrila a Metoda, UNB,Klinika hemat. a transfuz | Bratislava | |
| South Africa | Charlotte Maxeke Johannesburg Academic Hospital | Parktown, Johannesburg | Gauteng |
| South Africa | Pietersburg Hospital | Polokwane | Limpopo |
| Spain | Hospital Universitario La Paz | Madrid | |
| Spain | Hospital Universitario Regional de Málaga | Málaga | |
| Spain | Hospital Virgen del Rocío | Sevilla | |
| Spain | Hospital La Fe - Hemostasia y Trombosis | Valencia | |
| Sweden | Koagulationsmottagning | Malmö | |
| Sweden | Koagulationsmottagningen | Solna | |
| Switzerland | USZ Klinik für Medizinische Onkologie und Hämatologie | Zürich | |
| Thailand | Ramathibodi Hospital_Bangkok_0 | Bangkok | |
| Turkey | Acibadem Adana Hastanesi | Adana | |
| Turkey | Gazi University | Ankara | Besevler/Ankara |
| Turkey | Hacettepe University Medical Faculty | Ankara | |
| Turkey | Istanbul University Oncology Institute | Capa-ISTANBUL | |
| Turkey | Trakya University | Edirne | |
| Turkey | Ege Universitesi Tip Fakultesi | Izmir | |
| Turkey | Ondokuz Mayis University Medical Faculty Ped. Haematology | Samsun | |
| Ukraine | National specialized children clinic "OHMATDYT" | Kyiv | |
| Ukraine | Institute of blood pathology and transfusion medicine | Lviv | |
| United Kingdom | Belfast City Hospital | Belfast | |
| United Kingdom | Royal Free Haemophilia Comprehensive Care Center | London | |
| United Kingdom | Royal Hallamshire Hospital | Sheffield | |
| United States | Children's Hospital of Michigan | Detroit | Michigan |
| United States | M.S. Hershey Medical Center | Hershey | Pennsylvania |
| United States | Children's Hosp-Los Angeles | Los Angeles | California |
| United States | Versiti, CCBD | Milwaukee | Wisconsin |
| United States | Vanderbilt University Medical Center_Nashville_0 | Nashville | Tennessee |
| United States | Center for Inherited Blood Disorders | Orange | California |
| United States | University of Texas San Antonio | San Antonio | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Novo Nordisk A/S |
United States, Algeria, Australia, Bosnia and Herzegovina, Bulgaria, Canada, Croatia, Denmark, Estonia, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Lithuania, Malaysia, Mexico, Poland, Portugal, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, Ukraine, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes | This will be presented as 'count of episodes'. | 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) | |
| Primary | For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes | This will be presented as 'count of episodes'. | 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 | For haemophilia A patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes | This will be presented as 'count of episodes'. Arm 4 patients who have been on stable PPX at least 24 weeks in study 4322. For previous PPX (study 4322): From the point in time where PPX is stable and up until the end of study. Stable is defined as the time after an initial period on PPX treatment of at least 24 weeks. For concizumab PPX (trial 4307): From the point in time where the concizumab maintenance dose is confirmed, increased or decreased and up until the confirmatory analyses cut-off (at least 24 weeks). | Time frame is presented under 'outcome measure description' | |
| Secondary | For haemophilia B patients without inhibitors: The number of treated spontaneous and traumatic bleeding episodes | This will be presented as 'count of episodes'. Arm 4 patients who have been on stable PPX at least 24 weeks in study 4322. For previous PPX (study 4322): From the point in time where PPX is stable and up until the end of study. Stable is defined as the time after an initial period on PPX treatment of at least 24 weeks. For concizumab PPX (trial 4307): From the point in time where the concizumab maintenance dose is confirmed, increased or decreased and up until the confirmatory analyses cut-off (at least 24 weeks). | Time frame is presented under 'outcome measure description' | |
| Secondary | For haemophilia A patients without inhibitors: Number of treated spontaneous bleeding episodes | This will be presented as 'count of episodes'. | 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 | For haemophilia B patients without inhibitors: Number of treated spontaneous bleeding episodes | This will be presented as 'count of episodes'. | 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 | For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds | This will be presented as 'count of episodes'. | 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 | For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic joint bleeds | This will be presented as 'count of episodes'. | 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 | For haemophilia A patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds | This will be presented as 'count of episodes'. | 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 | For haemophilia B patients without inhibitors: Number of treated spontaneous and traumatic target joint bleeds | This will be presented as 'count of episodes'. | 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 | Number of thromboembolic events | This will be presented as 'count of events'. On demand (arm 1 main part): from randomisation to on demand treatment up until start of concizumab treatment. Concizumab (arms 2-4): Before the pause: From start of concizumab treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment (week 0) up until the confirmatory analyses cut-off (at least 32 weeks). Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the confirmatory analysis cut-off. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day). Week 0 after the pause is defined as the time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. | Time frame is presented under 'outcome measure description'. | |
| Secondary | Number of thromboembolic events | This will be presented as 'count of events'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day). | 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). | |
| Secondary | Number of hypersensitivity type reactions | This will be presented as 'count of hypersensitivity type reactions'. On demand (arm 1 main part): from randomisation to on demand treatment up until start of concizumab treatment. Concizumab (arms 2-4): Before the pause: From start of concizumab treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment (week 0) up until the confirmatory analyses cut-off (at least 32 weeks). Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the confirmatory analysis cut-off. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day). Week 0 after the pause is defined as the time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. | Time frame is presented under 'outcome measure description'. | |
| Secondary | Number of hypersensitivity type reactions | This will be presented as 'count of hypersensitivity type reactions'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day). | 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). | |
| Secondary | Number of injection site reactions | This will be presented as 'count of injection site reactions'. On demand (arm 1 main part): from randomisation to on demand treatment up until start of concizumab treatment. Concizumab (arms 2-4): Before the pause: From start of concizumab treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment (week 0) up until the confirmatory analyses cut-off (at least 32 weeks). Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the confirmatory analysis cut-off. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day). Week 0 after the pause is defined as the time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. | Time frame is presented under 'outcome measure description'. | |
| Secondary | Number of injection site reactions | This will be presented as 'count of injection site reactions'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day). | 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). | |
| Secondary | Number of patients with antibodies to concizumab | This will be presented as 'count of participants'. Concizumab (arms 2-4): Before the pause: From start of concizumab treatment (week 0) up until 7 weeks after the treatment was paused. After the pause: From start of concizumab treatment (week 0) up until the confirmatory analyses cut-off (at least 32 weeks). Concizumab (arm 1 extension part): From start of concizumab treatment (week 25) up until the confirmatory analysis cut-off. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day). Week 0 after the pause is defined as the time of randomisation to on-demand administration after the pause or time of start of the new concizumab dosing regimen. | Time frame is presented under 'outcome measure description'. | |
| Secondary | Number of patients with antibodies to concizumab | This will be presented as 'count of participants'. Week 0 before the pause is defined as the time of the initial randomisation to on-demand administration or time of start of the previous concizumab dosing regimen (0.25 mg/kg/day). | 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). | |
| Secondary | Pre-dose (trough) concizumab plasma concentration (Ctrough) | This will be measured in 'ng/mL'. | Prior to the concizumab administration at week 24 (after restart) | |
| Secondary | Pre-dose thrombin peak | This will be measured in 'nmol/L'. | Prior to the concizumab administration at week 24 (after restart) | |
| Secondary | Pre-dose free tissue factor pathway inhibitor (TFPI) concentration | This will be measured in 'ng/mL'. | Prior to the concizumab administration at week 24 (after restart) | |
| Secondary | Maximum concizumab plasma concentration (Cmax) | This will be measured in 'ng/mL'. | From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart) | |
| Secondary | Area under the concizumab plasma concentration-time curve (AUC) | This will be measured in 'ng*hr/mL'. | From 0 to 24 hours where 0 is time of the concizumab dose at week 24 (after restart) |