Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B.
- Conditions
- Haemophilia BCongenital Bleeding Disorder
- Interventions
- Registration Number
- NCT01467427
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
This trial is conducted in Asia, Europe and North America. The aim of the trial is to evaluate safety, efficacy and pharmacokinetics (the exposure of the trial drug in the body) of NNC-0156-0000-0009 (nonacog beta pegol, N9-GP) in previously treated children with Haemophilia B.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 25
- Male patients with moderately severe or severe congenital haemophilia B with a Factor IX activity level below or equal to 2% according to medical records
- Age below or equal to 12 years (until patient turns 13 years, at time of inclusion)
- Body weight above or equal to 10 kg
- History of at least 50 exposure days (EDs) to other FIX products
- The patient and/or parent(s)/caregiver are capable of assessing a bleeding episode, keeping an electronic diary (eDiary), capable of conducting home treatment and otherwise able to follow trial procedures
- Known history of FIX inhibitors
- Current FIX inhibitors above or equal to 0.6 Bethesda Units (BU)
- Congenital or acquired coagulation disorder other than haemophilia B
- Platelet count below 50,000/mcL at screening
- Alanine aminotransferase (ALT) above 3 times the upper limit of normal reference ranges at screening
- Creatinine level above or equal to 1.5 times above the upper normal limit of normal reference ranges at screening
- Human immunodeficiency virus (HIV) positive, defined by medical records, and with a CD4+ lymphocyte count below or equal to 200/mcL
- Immune modulating or chemotherapeutic medication (except single pulse treatment, inhaled and topical steroids)
- Previous arterial thrombotic events (myocardial infarction and intracranial thrombosis, as defined by medical records)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description NNC-0156-000-0009 nonacog beta pegol -
- Primary Outcome Measures
Name Time Method Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU) From week 52 to End of trial (EOT) (approximately week 544) Inhibitors were analysed with either the Nijmegen modified factor IX Bethesda assay or a heat/cold Nijmegen modified factor IX Bethesda assay. Number of participants who developed inhibitory antibodies against factor IX are reported.
- Secondary Outcome Measures
Name Time Method Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor) From week 0 to EOT (approximately week 544) Description of the haemostatic effect of nonacog beta pegol when used for treatment of bleeding episodes was measured and listed according to the four point scale for haemostatic response as below:
1. Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single infusion.
2. Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection.
3. Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one infusion within 8 hours.
4. Poor - no improvement, or worsening of symptoms within 8 hours after two injections.
A success rate was calculated based on counting good or excellent as successes and poor and moderate as failures.Incremental Recovery at 30 Minutes (IR30min) Week 0 (30 minutes after first exposure) The incremental recovery was calculated by dividing the baseline-subtracted factor IX activity Units per milliliter (U/mL) measured in plasma 30 min after dosing by the dose injected at time 0 expressed as units per kilogram (U/kg) body weight.
Trough Level (Single-dose ) Week 0 (one week after first exposure) The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. Geometric mean of the lowest activity of factor IX recorded at week 0 (immediately before next dose was given).
Terminal Half-life (t1/2) Week 0 (30 minutes until one week after first exposure) Terminal half life is presented at week 0, 30 minutes until one week after first exposure.
Trough Level (Steady State) From week 4 to EOT (approximately week 544) The mean pre-dose factor IX levels was measured with the one-stage clotting assay during the trial. The estimated mean of the lowest activity recorded immediately before next dose was given from week 4 to EOT approximately (week 544). Data is reported for specific age groups in which participants were a part of at any time from week 4 to EOT, not at specific time points assessed from week 4 to EOT. The analysis is based on a mixed model on the log-transformed plasma concentrations with participant as a random effect and the mean trough level is presented back-transformed to the natural scale. Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Number of Adverse Events Week 0 to EOT (approximately week 544) An adverse event (AE) was any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Here, data is presented for all adverse events (serious adverse events and other adverse events) from week 0 to EOT approximately (week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Number of Bleeding Episodes During Prophylaxis From week 0 to EOT (approximately week 544) The number of bleeding episodes per participant during routine prophylaxis was assessed using the individual annualised bleeding rates (bleeding episodes per participant per year).
Number of Serious Adverse Events (SAEs) Week 0 to EOT (approximately week 544) A SAE was an experience that at any dose resulted in any of the following: death, a life-threatening experience a), In-patient hospitalisation or prolongation of existing hospitalisation b) a persistent or significant disability/incapacity c) a congenital anomaly/birth defect, Important medical events d) that did not result in death, were life-threatening a) or required hospitalization. Here, data is presented from week 0 to EOT (approximately week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Medical Events of Special Interest (MESI) Week 0 to EOT (approximately week 544) The following events were defined as MESIs: -Medication errors concerning trial products, -Administration of wrong drug,
* Wrong route of administration,
* Administration of a high dose with the intention to cause harm, e.g. suicide attempt,
* Administration of an accidental overdose: more than 20 % from the intended dose,
* Inhibitor formation against factor IX (FIX),
* Thromboembolic events,
* Anaphylactic reaction.
* Allergic reaction including, but not limited to, any acute immunoglobulin E (IgE) mediated reaction or delayed type hypersensitivity.
Here, data is presented from week 0 to EOT (approximately week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.Development of Host Cell Protein (HCP) Antibodies From week 0 to EOT (approximately week 544) Participants were examined for the development of antibodies against HCP. Number of participants who developed antibodies against HCP is presented.
FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes From week 0 to EOT (approximately week 544) Consumption of nonacog beta pegol for treatment of bleeding episodes International units per kilogram per year (IU/Kg/year) per participant is presented from week 0 to EOT approximately (week 544). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes From week 0 to EOT (approximately week 544) Average dose of nonacog beta pegol for treatment of bleed from start to stop of bleed is presented from week 0 to EOT approximately (week 544) in international units per kilogram per bleed (IU/Kg/bleed). Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes From week 0 to EOT (approximately week 544) Number of doses of FIX consumed for the treatment of bleeding episodes is presented from week 0 to EOT approximately (week 544). Here, data of number of doses of FIX for the treatment of bleeding episodes is reported among all the participants in an arm. Data is reported for specific Age Groups in which participants were a part of at any time from week 0 to EOT, not at specific time points assessed from week 0 to EOT (approximately week 544). Considering the time frame, actual age groups (adolescents and adults) are added for this outcome measure.
Area Under the Curve Activity Versus Time Profile From Time Zero to 168 Hours Post Dose (AUC(0-168)) 0-168 hours post-dosing at week 0 Area under the curve activity versus time profile from time zero to 168 hours post dose of nonacog beta pegol is presented.
Clearance (CL) 0-168 hours post-dosing at week 0 Clearance of nonacog beta pegol after single dose is presented.
Volume of Distribution at Steady State (Vss) 0-168 hours post-dosing at week 0 Volume of distribution at steady state (Vss) of nonacog beta pegol is presented.
Mean Residence Time (MRT) 0-168 hours post-dosing at week 0 Mean residence time (MRT) of nonacog beta pegol after single dose is presented.
FIX Activity at 30 Minutes (C30min) (Single Dose) 30 min post-dosing at week 0 FIX activity (international units per milliliter (IU/mL)) at 30 minutes after single dose is presented.
Health Economic Impact of N9-GP Treatment Through Characterisation of Intensive Care Hospitalisation From week 0 to EOT (approximately week 544) Health economic impact of N9-GP treatment is presented through number of intensive care hospitalization days.
Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies From week 0 to EOT (approximately week 544) Health economic impact of N9-GP treatment through number of days bleedings caused missing school or studies. Number of participants who missed school or studies for 0,1 and 2 days are presented.
FIX Activity at 30 Minutes (C30min) (Steady State) 30 min post-dosing from week 4 to EOT (approximately week 544) Mean FIX activity at 30 minutes post-dosing from week 4 to EOT approximately (week 544) (C30min) (steady state) is presented.
TNO-AZL Preschool Quality of Life (TAPQOL) Screening (Week -6), week 52, week 176 approximately (visit 17) The Dutch institute of Prevention and Health and the Leiden University Hospital (TNO-AZL) preschool quality of life clustered into 12 multi-item scales is used to assess the health-related quality of life, such as children's motor, communication, emotions, and body structure. Suitable for children from 6 months to 6 years old (TAPQOL). Parents fill in according to the child's condition. Higher score (range 0-100) represents better outcome. The scale range for each of 12 multi-item scales was (0-100) with high score representing better outcome. In this study, the TAPQOL was assessed for children of age 0-3 years.
Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation From week 0 to EOT (approximately week 544) Number of participants with health economic impact of N9-GP treatment through characterisation of general hospitalisation is presented. Number of participants hospitalised for 0 \& 1 day is presented.
Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Using of Mobility Aids From week 0 to EOT (approximately week 544) Health economic impact of N9-GP treatment through number of days the patient used mobility aids (wheelchair and/or crutches) is presented.
Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Parents to Miss Work From week 0 to EOT (approximately week 544) Health economic impact of N9-GP treatment through number of days bleeding caused parents to miss work is presented from week 0 to EOT approximately (week 544).
Haemophilia-quality of Life (HAEMO-QOL) Screening (week -6), week 52, EOT (approximately week 544) Haemophilia quality of life clustered into 11 multi-item scale which is used to assess haemophilia related quality of life such as children's physical health, feeling, family, friends, sport, treatment, dealing with haemophilia, view of a patient. Here, HAEMO-QOL was assessed for the children of age group 8-12 years. The scale range for each of 11 multi-item scale was 0-100 with high scores indicating low quality of life. Multi-item scores and total score were calculated using the following formula: 1/4(Sum of answered items / number of answered items - 1) x 100. HAEMO-QOL scores range from a 0 to 100 scale where high scores (nearing 100) indicate a low quality of life rating.
Hemophilia Treatment Satisfaction (HEMO-SAT) Screening (Week -6), week 176 (visit 17) Haemophilia treatment satisfaction change from baseline (screening week -6) to week 176 (visit 17) is presented. The treatment satisfaction of a bleed with N8-GP was assessed using HEMO-SAT assessment tool which contains a questionnaire with 6 domains (Ease and convenience, efficacy, burden, specialist/nurses, centre/hospital, general satisfaction). The scale range for each 6 domains was (0-100) with lower score indicating higher treatment satisfaction. HEMO-SAT was assessed for the children of age group 4-7 years and 8-12 years. Domain score and total score were calculated using following formula - 1/4 (sum of answered items / Number of answered item - 1) x 100. HEMO-SAT scores range from 0-100, where low scores reflecting greater treatment satisfaction.
Trial Locations
- Locations (26)
Centre for Haemophilia, Haemostasis and Thrombosis
🇬🇧Basingstoke, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
National Blood Centre
🇲🇾Kuala Lumpur, Malaysia
NTU Hospital - Children and Women Hospital
🇨🇳Taipei, Taiwan
Hemorio-Fundarj
🇧🇷Rio de Janeiro, Brazil
Hôpital de la Timone
🇫🇷Marseille, France
Hopital Necker
🇫🇷Paris, France
MHH-pädiatrische Hämatologie
🇩🇪Hannover, Germany
Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano
🇮🇹Milano, MI, Italy
St. Marianna University School of Medicine Hospital_Pediatrics
🇯🇵Kanagawa, Japan
Shizuoka Children's Hospital, Hematology-Oncology
🇯🇵Shizuoka, Japan
Ogikubo Hospital_Pediatries & Blood
🇯🇵Tokyo, Japan
Children's Hosptl Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospitals And Clinics Of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
Mount Sinai Medical Center
🇺🇸New York, New York, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Vanderbilt Hemostasis Thrombosis Clinic
🇺🇸Nashville, Tennessee, United States
Children's Medical Center_Dallas
🇺🇸Dallas, Texas, United States
Nucleo de Pesquisa Instituto Pele Pequeno Principe
🇧🇷Curitiba, Parana, Brazil
Universidade Estadual de Campinas
🇧🇷Campinas, Sao Paulo, Brazil
The Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Clinical Hospital Centre Split, Firule, Paediatric Haem. Dpt
ðŸ‡ðŸ‡·Split, Croatia
Hopital de Bicetre
🇫🇷Le Kremlin Bicetre, France
St Thomas' Hospital
🇬🇧London, United Kingdom