Safety and Efficacy of Nonacog Beta Pegol (N9-GP) in Previously Untreated Patients With Haemophilia B
- Conditions
- Haemophilia BCongenital Bleeding Disorder
- Interventions
- Registration Number
- NCT02141074
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
This trial is conducted globally. The aim of the trial is to investigate the safety and efficacy of nonacog beta pegol (N9-GP) in previously untreated patients with Haemophilia B.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 54
- 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, age below 6 years at the time of signing informed consent
- Patients with the diagnosis of haemophilia B (FIX (coagulation factor IX) activity level below or equal to 2%) based on medical records or central laboratory results
- Previously untreated or exposed to FIX containing products less than or equal to 3 exposure days (5 previous exposures to blood components is acceptable)
- Any history of FIX inhibitors (defined by medical records)
- Known or suspected hypersensitivity to trial product or related products
- Previous participation in this trial. Participation is defined as first dose administered of trial product
- Receipt of any investigational medicinal product within 30 days before screening
- Congenital or acquired coagulation disorder other than haemophilia B
- Any chronic disorder or severe disease which, in the opinion of the Investigator, might jeopardise the patient's safety or compliance with the protocol
- Patient's parent(s)/LAR(s) (legally acceptable representative) mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 50 EDs (exposure days) nonacog beta pegol -
- Primary Outcome Measures
Name Time Method Number of Participants With Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) (50 Exposure Days) When minimum 20 previously untreated patients (PUPs) have reached at least 50 exposure days (ED) (up to 156 weeks) Number of participants with incidence of inihibitory antibodies against FIX after 50 ED is presented and defined as an inhibitory antibody titre greater than equal to 0.6 Bethesda unit (BU) at two consecutive tests performed at the central laboratory and also tested positive for nonacog beta pegol binding antibodies.
Number of Participants With Incidence of Inhibitory Antibodies Against FIX (100 ED) When minimum 40 PUPs have reached at least 100 ED (up to 208 weeks) Number of participants with incidence of inihibitory antibodies against FIX after 100 ED is presented and defined as an inhibitory antibody titre greater than equal to 0.6 Bethesda unit (BU) at two consecutive tests performed at the central laboratory and also tested positive for nonacog beta pegol binding antibodies.
Number of Participants With Incidence of Inhibitory Antibodies Against FIX (At End of Trial) At end of trial (up to 434 weeks) Number of participants with incidence of inihibitory antibodies against FIX at end of trial is presented and defined as an inhibitory antibody titre greater than equal to 0.6 Bethesda unit (BU) at two consecutive tests performed at the central laboratory and also tested positive for nonacog beta pegol binding antibodies.
- Secondary Outcome Measures
Name Time Method Frequency of Adverse Events When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Frequency of adverse events after 50 ED, after 100 ED, and at end of trial is presented. Frequency of adverse events was expressed as number of adverse events per participant years of exposure (total number of events /total time in trial). An adverse event was defined as any untoward medical occurrence in a participant who was administered a product, and which does not necessarily have a causal relationship with this treatment. All presented adverse events are treatment emergent adverse events, defined as an event that occured while the participant was on treatment in the period from first dosing with nonacog beta pegol to the end of trial/discontinuation of treatment.
Number of Injections Needed to Treat a Bleeding Episode When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) The mean number of injections needed to treat a bleeding episode is presented.
Frequency of Medical Events of Special Interest When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Frequency of medical events of special interest after 50 ED, after 100 ED, and at end of trial is presented. It was expressed as number of MESI per participant years of exposure (total number of events/total time in trial). A MESI was an event that, in the evaluation of safety, has a special focus. A MESI was an adverse event that fulfils one or more of the MESI criteria: 1. Medication errors concerning the trial product; 2. Inhibitor formation against FIX; 3. Thromboembolic events; 4. Anaphylactic reaction; 5. Allergic reaction including, but not limited to, any acute immunoglobulin E mediated reaction of delayed-type hypersensitivity (clinical signs may include various types of skin rashes) that does not meet the definition of anaphylaxis; 6. CNS-related adverse events including, but not limited to, any learning and behavioral deficits; 7. Renal adverse events including new onset of renal disorder or renal impairment or acute and chronic renal failure.
FIX Activity at 30 Minutes (C30min) When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks) FIX Activity 30 minutes post dosing (C30min) after 50 ED, after 100 ED is presented. The FIX activity was measured by one-stage clotting assay - a modified activated partial thromboplastin time (aPTT) assay.
Amount of Drug Administered to Treat a Bleeding Episode When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Amount of nonacog beta pegol administered (average dose of nonacog beta pegol) to treat a bleeding episode after 50 ED, after 100 ED, and at end of trial is presented as international units per kilogram per bleed (IU/kg/bleed).
Number of Adverse Events When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Number of adverse events after 50 ED, after 100 ED, and at end of trial is presented. An adverse event was defined as any untoward medical occurrence in a participant who was administered a product, and which does not necessarily have a causal relationship with this treatment. All presented adverse events are treatment emergent adverse events, defined as an event that occured while the participant was on treatment in the period from first dosing with nonacog beta pegol to the end of trial/discontinuation of treatment.
Number of Breakthrough Bleeding Episodes During Prophylaxis (Annualised Bleeding Rate) When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Number of breakthrough bleeding episodes during prophylaxis (annualised bleeding rate) after 50 ED, after 100 ED, and at end of trial is presented. Annualised bleeding rate is the number of bleeding episodes per year.
Number of Serious Adverse Events When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Number of serious adverse events after 50 ED, after 100 ED, and at end of trial is presented. A serious adverse event was an experience that at any dose resulted in: death; life-threatening experience; in-patient hospitalisation or prolongation of existing hospitalisation; a persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events that may not result in death, be life-threatening/require hospitalisation could be considered a serious adverse event based upon appropriate medical judgement.
Frequency of Serious Adverse Events When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Frequency of serious adverse events after 50 ED, after 100 ED, and at end of trial is presented. Frequency of serious adverse events was expressed as number of serious adverse events per participant years of exposure (total number of events /total time in trial). A serious adverse event was an experience that at any dose resulted in: death; life-threatening experience; in-patient hospitalisation or prolongation of existing hospitalisation; a persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical events that may not result in death, be life-threatening/require hospitalisation could be considered a serious adverse event based upon appropriate medical judgement.
Haemostatic Effect of Nonacog Beta Pegol in Treatment of Bleeding Episodes by 4-point Haemostatic Response Scale ("Excellent", "Good", "Moderate" and "Poor") When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Haemostatic effect of nonacog beta pegol in treatment of bleeding episodes by 4-point haemostatic response scale after 50 ED, after 100 ED, and at end of trial is presented. The haemostatic response after treatment of a bleed with nonacog beta pegol was evaluated on a 4-point scale as excellent, good, moderate or poor. Excellent: abrupt pain relief and/or clear improvement in objective signs of bleeding; Good: noticeable pain relief and/or improvement in signs of bleeding; Moderate: probable or slight beneficial effect after the first injection; Poor: no improvement or worsening of symptoms. If the haemostatic response was rated as excellent or good, the treatment of the bleed was considered a success. If the haemostatic response was rated as moderate or poor, the treatment was considered a failure.
Incremental Recovery at 30 Minutes (IR30min) When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks) Incremental recovery 30 minutes post dosing (IR30min) after 50 ED, after 100 ED is presented. IR30min was defined as the rise in FIX activity per international units per kilogram (IU/kg) administered and was recorded 30 minutes after the end of nonacog beta pegol injection. It was calculated as the baseline adjusted FIX activity recorded 30 minutes after ended nonacog beta pegol injection divided by the administered dose (IU/kg body weight). It was recorded as international units per milliliter (IU/mL)/international units per kilogram (IU/kg).
FIX Trough Levels When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) FIX trough levels after 50 ED, after 100 ED, and at end of trial is presented. FIX trough level was defined as the activity recorded immediately before nonacog beta pegol injection was given and was measured by one-stage clotting assay - a modified activated partial thromboplastin time (aPTT) assay. The analysis is based on a mixed model on the log-transformed plasma concentrations with participant as a random effect. The mean trough level is presented back-transformed to the natural scale.
Number of Medical Events of Special Interest When minimum 20 PUPs have reached at least 50 ED (up to 156 weeks); when minimum 40 PUPs have reached at least 100 ED (up to 208 weeks); at end of trial (up to 434 weeks) Number of medical events of special interest after 50 ED, after 100 ED, and at end of trial is presented. A medical event of special interest (MESI) was an event that, in the evaluation of safety, has a special focus. A MESI was an adverse event (serious or non-serious adverse event) that fulfils one or more of the following MESI criteria: 1. Medication errors concerning the trial product; 2. Inhibitor formation against FIX; 3. Thromboembolic events; 4. Anaphylactic reaction; 5. Allergic reaction including, but not limited to, any acute immunoglobulin E mediated reaction of delayed-type hypersensitivity (clinical signs may include various types of skin rashes) that does not meet the definition of anaphylaxis; 6. CNS-related adverse events including, but not limited to, any learning and behavioral deficits; 7. Renal adverse events including new onset of renal disorder or renal impairment or acute and chronic renal failure.
Trial Locations
- Locations (45)
Landes-Frauen und Kinderklinik Linz
🇦🇹Linz, Austria
LKH Salzburg- Univ. Klinik f. Kinder- und Jugendheilkunde
🇦🇹Salzburg, Austria
Children's Hospital Los Angeles - Endocrinology
🇺🇸Los Angeles, California, United States
St. Luke's Mountain States Tumor Institute
🇺🇸Boise, Idaho, United States
Children's Hosp-New Orleans
🇺🇸New Orleans, Louisiana, United States
Univ of NE Med Center_Omaha
🇺🇸Omaha, Nebraska, United States
St.Jude Clin at Novant Hlth Hemby Cld Hosp
🇺🇸Charlotte, North Carolina, United States
Univ Hosp Cleveland Med Ctr
🇺🇸Cleveland, Ohio, United States
Children's Medical Center
🇺🇸Dayton, Ohio, United States
St Christopher Hosp for Child
🇺🇸Philadelphia, Pennsylvania, United States
Vanderbilt Hemostasis Thrombosis Clinic
🇺🇸Nashville, Tennessee, United States
Univ of Utah Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Beni Messous Hospital Issaad Hassani
🇩🇿Algiers, Algeria
University Hospital Saadna Abdenour of Setif
🇩🇿Setif, Algeria
Hospital de Pediatría S.A.M.I.C. "Prof. Dr. Juan P. Garrahan
🇦🇷Caba, Argentina
Sanatorio Mayo Privado S.A
🇦🇷Cordoba, Argentina
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Med. Univ. Graz -Klinische Abteilung f. Allgemeine Pädiatrie
🇦🇹Graz, Austria
Universitätsklinik Kinder-Jugendheilkunde
🇦🇹Innsbruck, Austria
Klinikum Klagenfurt am Wörthersee (LKH Klagenfurt)
🇦🇹Klagenfurt, Austria
Ordination Prof. Zwiauer
🇦🇹St. Poelten, Austria
Universitätsklinik für Kinder- und Jugendheilkunde
🇦🇹Wien, Austria
Hamltn Hth Sci/McMstr Child Hosp
🇨🇦Hamilton, Ontario, Canada
CHU Estaing
🇫🇷Clermont Ferrand, France
Hopital de Bicetre
🇫🇷Kremlin-Bicêtre, France
Sheba MC The Israeli National Hemophilia Center
🇮🇱Tel-Hashomer, Israel
Centre régional de traitement de l'Hémophilie
🇫🇷Nantes Cedex 1, France
Saitama Children's Med Centre_Hematology-Oncology
🇯🇵Saitama, Japan
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Pahang, Malaysia
Hospital Pulau Pinang_Georgetown, Penang
🇲🇾Georgetown, Penang, Malaysia
Hospital Tengku Ampuan Rahimah
🇲🇾Klang, Selangor, Malaysia
National Blood Centre
🇲🇾Kuala Lumpur, Malaysia
Hospital Sant Joan de Déu
🇪🇸Esplugues Llobregat, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital La Fe - Endocrinología y Nutrición
🇪🇸Valencia, Spain
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital_Kaohsiung
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital - Children Building
🇨🇳Taichung, Taiwan
NTU Hospital - Children and Women Hospital
🇨🇳Taipei, Taiwan
Ramathibodi Hospital_Bangkok
🇹🇭Bangkok, Thailand
Hematology and Oncology, Dept.of Pediatrics, CMU
🇹🇭Chiang Mai, Thailand
Birmingham Children's Hospital
🇬🇧Birmingham, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
St Thomas' Hospital
🇬🇧London, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom