Clinical trial NCT01467427: Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B.
Official title: Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congenital Bleeding Disorder
Haemophilia B
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2011-11-08
Enrollment: 25
Sex: MALE
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU)
timeFrame: From week 0 to week 52
measure: Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU)
timeFrame: From week 52 to End of trial (EOT) (approximately week 544)
Secondary outcomes:
measure: Number of Bleeding Episodes During Prophylaxis
timeFrame: From week 0 to EOT (approximately week 544)
measure: Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor)
timeFrame: From week 0 to EOT (approximately week 544)
measure: Incremental Recovery at 30 Minutes (IR30min)
timeFrame: Week 0 (30 minutes after first exposure)
measure: Trough Level (Single-dose )
timeFrame: Week 0 (one week after first exposure)
measure: Terminal Half-life (t1/2)
timeFrame: Week 0 (30 minutes until one week after first exposure)
measure: Trough Level (Steady State)
timeFrame: From week 4 to EOT (approximately week 544)
measure: Number of Adverse Events
timeFrame: Week 0 to EOT (approximately week 544)
measure: Number of Serious Adverse Events (SAEs)
timeFrame: Week 0 to EOT (approximately week 544)
measure: Medical Events of Special Interest (MESI)
timeFrame: Week 0 to EOT (approximately week 544)
measure: Development of Host Cell Protein (HCP) Antibodies
timeFrame: From week 0 to EOT (approximately week 544)
measure: FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes
timeFrame: From week 0 to EOT (approximately week 544)
measure: FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes
timeFrame: From week 0 to EOT (approximately week 544)
measure: Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes
timeFrame: From week 0 to EOT (approximately week 544)
measure: Area Under the Curve Activity Versus Time Profile From Time Zero to 168 Hours Post Dose (AUC(0-168))
timeFrame: 0-168 hours post-dosing at week 0
measure: Clearance (CL)
timeFrame: 0-168 hours post-dosing at week 0
measure: Mean Residence Time (MRT)
timeFrame: 0-168 hours post-dosing at week 0
measure: Volume of Distribution at Steady State (Vss)
timeFrame: 0-168 hours post-dosing at week 0
measure: FIX Activity at 30 Minutes (C30min) (Single Dose)
timeFrame: 30 min post-dosing at week 0
measure: FIX Activity at 30 Minutes (C30min) (Steady State)
timeFrame: 30 min post-dosing from week 4 to EOT (approximately week 544)
measure: TNO-AZL Preschool Quality of Life (TAPQOL)
timeFrame: Screening (Week -6), week 52, week 176 approximately (visit 17)
measure: Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation
timeFrame: From week 0 to EOT (approximately week 544)
measure: Health Economic Impact of N9-GP Treatment Through Characterisation of Intensive Care Hospitalisation
timeFrame: From week 0 to EOT (approximately week 544)
measure: Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies
timeFrame: From week 0 to EOT (approximately week 544)
measure: Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Using of Mobility Aids
timeFrame: From week 0 to EOT (approximately week 544)
measure: Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Parents to Miss Work
timeFrame: From week 0 to EOT (approximately week 544)
measure: Haemophilia-quality of Life (HAEMO-QOL)
timeFrame: Screening (week -6), week 52, EOT (approximately week 544)
measure: Hemophilia Treatment Satisfaction (HEMO-SAT)
timeFrame: Screening (Week -6), week 176 (visit 17)
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Children's Hospitals And Clinics Of Minnesota
state: Minnesota
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hosptl Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Hemostasis Thrombosis Clinic
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center_Dallas
state: Texas
city: Curitiba
country: Brazil
facility: Nucleo de Pesquisa Instituto Pele Pequeno Principe
state: Parana
city: Campinas
country: Brazil
facility: Universidade Estadual de Campinas
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
facility: Hemorio-Fundarj
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Split
country: Croatia
facility: Clinical Hospital Centre Split, Firule, Paediatric Haem. Dpt
city: Le Kremlin Bicetre
country: France
facility: Hopital de Bicetre
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Hopital Necker
city: Hannover
country: Germany
facility: MHH-pädiatrische Hämatologie
city: Milano
country: Italy
facility: Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano
state: MI
city: Kanagawa
country: Japan
facility: St. Marianna University School of Medicine Hospital_Pediatrics
city: Shizuoka
country: Japan
facility: Shizuoka Children's Hospital, Hematology-Oncology
city: Tokyo
country: Japan
facility: Ogikubo Hospital_Pediatries & Blood
city: Kuala Lumpur
country: Malaysia
facility: National Blood Centre
city: Taipei
country: Taiwan
facility: NTU Hospital - Children and Women Hospital
city: Basingstoke
country: United Kingdom
facility: Centre for Haemophilia, Haemostasis and Thrombosis
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
References:
citation: Safety, efficacy and pharmacokinetics of nonacog beta pegol (N9-GP) in prophylaxis and treatment of bleeding episodes in previously treated pediatric hemophilia B patients. Carcao M, Zak M, Abdul Karim F, Hanabusa H, Kearney S, Lu M-Y, Persson P, Rangarajan S, Santagostino E. Presented 06-Dec-2014 at the American Society of Hematology - 56th Annual Meeting - held in San Francisco, CA, US (poster #1513)
citation: Carcao M, Zak M, Abdul Karim F, Hanabusa H, Kearney S, Lu MY, Persson P, Rangarajan S, Santagostino E. Nonacog beta pegol in previously treated children with hemophilia B: results from an international open-label phase 3 trial. J Thromb Haemost. 2016 Aug;14(8):1521-9. doi: 10.1111/jth.13360. Epub 2016 Jun 22.
citation: Carcao M, Kearney S, Lu MY, Taki M, Rubens D, Shen C, Santagostino E. Long-Term Safety and Efficacy of Nonacog Beta Pegol (N9-GP) Administered for at Least 5 Years in Previously Treated Children with Hemophilia B. Thromb Haemost. 2020 May;120(5):737-746. doi: 10.1055/s-0040-1709521. Epub 2020 May 5.