Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B. (paradigm™5)

Safety, Efficacy and Pharmacokinetics of NNC-0156-0000-0009 in Previously Treated Children With Haemophilia B

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.

Study Overview

• Status: Completed
• Conditions: Congenital Bleeding Disorder; Haemophilia B
• Intervention / Treatment: Drug: nonacog beta pegol

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 20211-030
    • Hemorio-Fundarj
  • Paraná
    • Curitiba, Paraná, Brazil, 80250-060
      • Nucleo de Pesquisa Instituto Pele Pequeno Principe
  • São Paulo
    • Campinas, São Paulo, Brazil, 13081-970
      • Universidade Estadual De Campinas
    • São Paulo, São Paulo, Brazil, 05403-000
      • Hospital das Clinicas da Faculdade de Medicina da USP
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• Croatia
  • Split, Croatia, 21 000
    • Clinical Hospital Centre Split, Firule, Paediatric Haem. Dpt
• France
  • Le Kremlin-Bicêtre, France, 94275
    • Ap-Hp-Hopital de Bicetre-1
  • Marseille, France, 13385
    • Hôpital de la Timone
  • Paris, France, 75015
    • Ap-Hp-Hopital Necker-1
• Germany
  • Duisburg, Germany, 47051
    • Coagulation Research Center
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover - Pädiatrische Hämato-, Onko- und Hämostasiologie
• Italy
  • MI
    • Milan, MI, Italy, 20124
      • Istituto di Medicina Int. A. Bianchi Bonomi Univ. Milano
• Japan
  • Kanagawa, Japan, 216-8511
    • St. Marianna University School of Medicine Hospital_Pediatrics
  • Shizuoka, Japan, 420-8660
    • Shizuoka Children's Hospital, Hematology-Oncology
  • Tokyo, Japan, 167-0035
    • Ogikubo Hospital_Pediatries & Blood
• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • National Blood Centre
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Children's Hospital
• Turkey (Türkiye)
  • Konya, Turkey (Türkiye), 42090
    • Necmettin Erbakan University Pediatric Hematology
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9NA
    • Basingstoke & North Hampshire Hospital - Centre for Haemophilia, Haemostasis and Thrombosis
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary - Haemostasis & Thrombosis Unit
  • London, United Kingdom, SE1 7EH
    • St Thomas' Hospital
  • London, United Kingdom, SE1 7EH
    • St Thomas' Hospital - Haemostasis and Thrombosis Centre
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles - Endocrinology
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Colorado Hemophilia & Thrombosis Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010-2978
      • Childrens National Medical Ctr
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital & Clinics
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University_Atlanta_1
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University Of Louisville_Louisville_0
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University_Baltimore_3
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64108-4619
      • The Children's Mercy Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Univ of NE Med Center_Omaha
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers-Robert Wood Johnson Medical School
  • New York
    • Brooklyn, New York, United States, 11220
      • Maimonides Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Univ Hosp Cleveland Med Ctr
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404
      • Dayton Children Hemostati Ctr
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Univ Oklahoma Sci Ctr OK City
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hosptl Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Hemostasis Thrombosis Clinic
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center_Dallas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital_Houston
    • Houston, Texas, United States, 77030
      • Univ TX Hlth Sci Ctr Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NNC-0156-000-0009	Drug: nonacog beta pegol; A single dose of 40 U/kg will be administered intravenously, i.v. (into the vein) once weekly.; Other Names: NNC-0156-0000-0009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU)	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.	From week 0 to week 52
Incidence of Inhibitory Antibodies Against Coagulation Factor IX (FIX) Defined as Titre Above or Equal to 0.6 Bethesda Units (BU)	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.	From week 52 to End of trial (EOT) (approximately week 544)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Level (Single-dose )	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).	Week 0 (one week after first exposure)
Area Under the Curve Activity Versus Time Profile From Time Zero to 168 Hours Post Dose (AUC(0-168))	Area under the curve activity versus time profile from time zero to 168 hours post dose of nonacog beta pegol is presented.	0-168 hours post-dosing at week 0
Clearance (CL)	Clearance of nonacog beta pegol after single dose is presented.	0-168 hours post-dosing at week 0
Mean Residence Time (MRT)	Mean residence time (MRT) of nonacog beta pegol after single dose is presented.	0-168 hours post-dosing at week 0
Volume of Distribution at Steady State (Vss)	Volume of distribution at steady state (Vss) of nonacog beta pegol is presented.	0-168 hours post-dosing at week 0
Number of Bleeding Episodes During Prophylaxis	The number of bleeding episodes per participant during routine prophylaxis was assessed using the individual annualised bleeding rates (bleeding episodes per participant per year).	From week 0 to EOT (approximately week 544)
Haemostatic Effect of N9-GP in Treatment of Bleeding Episodes by 4-point Categorical Scale for Haemostatic Response (Excellent, Good, Moderate and Poor)	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: Excellent - abrupt pain relief and/or clear improvement in objective signs of bleeding within 8 hours after a single infusion.; Good - noticeable pain relief and/or improvement in signs of bleeding within 8 hours after a single injection.; Moderate - probable or slight beneficial effect within the first 8 hours after the first injection but requiring more than one infusion within 8 hours.; 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.	From week 0 to EOT (approximately week 544)
Incremental Recovery at 30 Minutes (IR30min)	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.	Week 0 (30 minutes after first exposure)
Terminal Half-life (t1/2)	Terminal half life is presented at week 0, 30 minutes until one week after first exposure.	Week 0 (30 minutes until one week after first exposure)
Trough Level (Steady State)	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.	From week 4 to EOT (approximately week 544)
Number of Adverse Events	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.	Week 0 to EOT (approximately week 544)
Number of Serious Adverse Events (SAEs)	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.	Week 0 to EOT (approximately week 544)
Medical Events of Special Interest (MESI)	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.	Week 0 to EOT (approximately week 544)
Development of Host Cell Protein (HCP) Antibodies	Participants were examined for the development of antibodies against HCP. Number of participants who developed antibodies against HCP is presented.	From week 0 to EOT (approximately week 544)
FIX Consumption Described as Frequency of Dose/kg for Prophylaxis Use for the Treatment of Bleeding Episodes	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.	From week 0 to EOT (approximately week 544)
FIX Consumption Described as Amount Consumed for the Treatment of Bleeding Episodes	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.	From week 0 to EOT (approximately week 544)
Number of Doses of FIX Consumed for the Treatment of Bleeding Episodes	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.	From week 0 to EOT (approximately week 544)
FIX Activity at 30 Minutes (C30min) (Single Dose)	FIX activity (international units per milliliter (IU/mL)) at 30 minutes after single dose is presented.	30 min post-dosing at week 0
FIX Activity at 30 Minutes (C30min) (Steady State)	Mean FIX activity at 30 minutes post-dosing from week 4 to EOT approximately (week 544) (C30min) (steady state) is presented.	30 min post-dosing from week 4 to EOT (approximately week 544)
TNO-AZL Preschool Quality of Life (TAPQOL)	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.	Screening (Week -6), week 52, week 176 approximately (visit 17)
Number of Participants With Health Economic Impact of N9-GP Treatment Through Characterisation of General Hospitalisation	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.	From week 0 to EOT (approximately week 544)
Health Economic Impact of N9-GP Treatment Through Characterisation of Intensive Care Hospitalisation	Health economic impact of N9-GP treatment is presented through number of intensive care hospitalization days.	From week 0 to EOT (approximately week 544)
Health Economic Impact of N9-GP Treatment Through Characterisation of Bleedings Caused Missing School or Studies	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.	From week 0 to EOT (approximately week 544)
Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Using of Mobility Aids	Health economic impact of N9-GP treatment through number of days the patient used mobility aids (wheelchair and/or crutches) is presented.	From week 0 to EOT (approximately week 544)
Health Economic Impact of N9-GP Treatment Through Characterisation of Number of Days Bleedings Caused Parents to Miss Work	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).	From week 0 to EOT (approximately week 544)
Haemophilia-quality of Life (HAEMO-QOL)	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.	Screening (week -6), week 52, EOT (approximately week 544)
Hemophilia Treatment Satisfaction (HEMO-SAT)	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.	Screening (Week -6), week 176 (visit 17)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• 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)
• 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.
• 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.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2012
• Primary Completion (Actual): November 17, 2023
• Study Completion (Actual): November 17, 2023

Study Registration Dates

• First Submitted: October 31, 2011
• First Submitted That Met QC Criteria: November 4, 2011
• First Posted (Estimated): November 8, 2011

Study Record Updates

• Last Update Posted (Estimated): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Genetic Diseases, X-Linked; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia B; nonacog beta pegol
• Other Study ID Numbers: NN7999-3774; 2011-000826-31 (EudraCT Number); U1111-1119-5013 (Other Identifier: WHO); JapicCTI- 121877 (Registry Identifier: JAPIC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordiskdisclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No