Safety and Efficacy of Turoctocog Alfa Pegol (N8-GP) in Previously Untreated Patients With Haemophilia A (pathfinder™6)

An Open-label Single-arm Multicentre Non-controlled Phase 3a Trial Investigating Safety and Efficacy of N8-GP in Prophylaxis and Treatment of Bleeding Episodes in Previously Untreated Paediatric Patients With Severe Haemophilia A

This trial is conducted globally. The aim of the trial is to investigate the safety and efficacy of turoctocog alfa pegol (N8-GP) in previously untreated patients (PUPs) with haemophilia A.

Study Overview

• Status: Completed
• Conditions: Congenital Bleeding Disorder; Haemophilia A
• Intervention / Treatment: Drug: turoctocog alfa pegol

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 3

Contacts and Locations

Study Locations

• Algeria
  • Algiers, Algeria, 16000
    • Beni Messous Hospital Issaad Hassani
  • Sétif, Algeria, 19000
    • University Hospital Saadna Abdenour of Setif
• Argentina
  • CABA, Argentina, C1245AAM
    • Hospital de Pediatría S.A.M.I.C. "Prof. Dr. Juan P. Garrahan
  • Córdoba, Argentina, X5000FAL
    • Sanatorio Mayo Privado S.A
• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Lady Cilento Children's Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
• Austria
  • Graz, Austria, 8036
    • Med. Univ. Graz -Klinische Abteilung f. Allgemeine Pädiatrie
  • Innsbruck, Austria, 6020
    • Universitätsklinik Kinder-Jugendheilkunde Innsbruck
  • Klagenfurt, Austria, 9020
    • Klinikum Klagenfurt am Wörthersee (LKH Klagenfurt)
  • Linz, Austria, 4020
    • Landes-Frauen und Kinderklinik Linz
  • Salzburg, Austria, 5020
    • LKH Salzburg- Univ. Klinik f. Kinder- und Jugendheilkunde
  • Sankt Pölten, Austria, 3100
    • LKH St. Poelten, Kinder-und Jugendheilkunde
  • Vienna, Austria, A 1090
    • Universitätsklinik für Kinder- und Jugendheilkunde
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • UMHAT Sveti Georgi EAD, Plovdiv, Clinic of Pediatrics
• Canada
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Health Science Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamltn Hth Sci/McMstr Child Hosp
• France
  • Bron, France, 69500
    • Hospices Civils de Lyon- Hopital Louis Pradel-1
  • Clermont-Ferrand, France, 63003
    • CHU Estaing
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire de Nantes-Hopital Hotel-Dieu
  • Paris, France, 75015
    • Ap-Hp-Hopital Necker-1
  • Paris La Défense, France, 92936
    • Master centre for France
• Germany
  • Duisburg, Germany, 47051
    • Coagulation Research Center
  • Frankfurt am Main, Germany, 60596
    • HZRM Haemophilie-Zentrum Rhein Main GmbH
  • Hanover, Germany, 30159
    • Werlhof-Institut
  • Hanover, Germany
    • Werlhof-Institut
  • Homburg/Saar, Germany, 66424
    • Universitätsklinikum des Saarlandes - Pädiatrische Onkologie und Hämatologie
• Greece
  • Athens, Greece, GR-11527
    • Aghia Sophia Childrens' Hospital
  • Thessaloniki, Greece, 54642
    • 'Ippokrateio' General Hospital of Thessaloniki
• Israel
  • Tel Litwinsky, Israel, 52621
    • Sheba MC - The Israeli National Hemophilia Center
• Italy
  • Florence, Italy, 50139
    • IRCCS Meyer Firenze
  • Florence, Italy, 50134
    • Dipartimento di Ematologia Univ. Firenze
  • Torino, Italy, 10126
    • A.O.U. Città della Salute e della Scienza di Torino-Ospedale
• Japan
  • Aichi, Japan, 466-8560
    • Nagoya University Hospital_Blood Transfusion
  • Hyōgo, Japan, 654-0047
    • Hyogo Prefectural Kobe Children's Hospital
  • Kyoto, Japan, 602-8566
    • Univ.HP, Kyoto Pref Univ of Medicine, Dept. of Pediatrics
  • Saitama, Japan, 330-8777
    • Saitama Children's Med Centre_Hematology-Oncology
  • Shizuoka, Japan, 420-8660
    • Shizuoka Children's Hospital, Hematology-Oncology
  • Tokyo, Japan, 157-8535
    • National Center for Child Health and Development_Hematology
• Malaysia
  • Kuala Lumpur, Malaysia, 50400
    • National Blood Centre
  • Kuala Lumpur, Malaysia, 50300
    • Hospital Wanita Dan Kanak-Kanak Kuala Lumpur
  • Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10450
      • Hospital Pulau Pinang_Georgetown, Penang
• Mexico
  • México, D.F.
    • Mexico City, México, D.F., Mexico, 06720
      • Centro Medico Nacional SXXI-Hospital de Pediatria, IMSS
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario Dr. José Eleuterio González_Monterrey
• Portugal
  • Lisbon, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte-HSM
  • Porto, Portugal, 4200-319
    • ULS São João, E.P.E.
• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • Pediatric Hemophilia Program University
• Romania
  • Bucharest, Romania, 022328
    • 1st Paediatric Department, Fundeni Clinical Institute
  • Constanța, Romania, 900591
    • Emergency County Hospital Constanta
  • Timiș County
    • Timișoara, Timiș County, Romania, 300011
      • ,,Louis Ţurcanu'' Emergency Hospital for Children
• Serbia
  • Belgrade, Serbia, 11000
    • University Children's Hospital Tirsova
• Spain
  • A Coruña, Spain, 15006
    • Hospital Teresa Herrera Materno Infantil . E.O.X.I. A Coruña
  • Esplugues Llobregat, Spain, 08950
    • Hospital Sant Joan de Déu
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital_Hematology Dept.
  • Kaohsiung City, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital_Dept of Pediatrics
  • Taichung, Taiwan, 40447
    • China Medical University Children's Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Children's Hospital
• Thailand
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital_Paediatrics
  • Chiang Mai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai Hospital _Pediatric Hematology and Oncology
  • Mueang Distirct,
    • Ubon Ratchathani, Mueang Distirct,, Thailand, 34000
      • Sunpasitthiprasong Hospital_Pediatrics Department
• Ukraine
  • Donetsk, Ukraine, 83045
    • SI Institute of Urgent and Recovery Surgery - Haematology
  • Lviv, Ukraine, 79044
    • Institute of blood pathology and transfusion medicine of NAMSU - General and haematol. surgery
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Arizona H&T Phoenix Child Hosp
  • California
    • Long Beach, California, United States, 90806
      • Miller Children's Hospital Long Beach
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles - Endocrinology
    • Orange, California, United States, 92868-3835
      • Children's Hosp Of Orange
    • Torrance, California, United States, 90502-2004
      • Harbor-UCLA Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • Shands Hospital at the University of Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Chld Clnc Jacksonville
    • Orlando, Florida, United States
      • Nemours Child Orlando Hem/Onc
    • Tampa, Florida, United States, 33607
      • St Joseph's Hospital Foundation
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University_Atlanta_1
    • Augusta, Georgia, United States, 30912
      • Medical College of Georgia
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Mountain States Tumor Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Med. Cntr
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70118-5720
      • Children's Hosp-New Orleans
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6828
      • Univ of NE Med Center_Omaha
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • Hemostasis and Thrombosis Center of Nevada
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers-Robert Wood Johnson Medical School
  • New York
    • Brooklyn, New York, United States, 11201-5425
      • The Brooklyn Hsptl Center
    • New Hyde Park, New York, United States, 11042
      • North Shore Long Island Jewish Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Torrence Hemby Ped Hem/Onc Ctr
    • Charlotte, North Carolina, United States, 28204
      • Novant Hlth Vasc Ins Charlotte
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Univ Hosp Cleveland Med Ctr
    • Dayton, Ohio, United States, 45404
      • Dayton Children Hemostati Ctr
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Univ Oklahoma Sci Ctr OK City
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University_Portland_5
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • St Christopher Hosp for Child
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hosptl Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University Of SC
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Hemostasis Thrombosis Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Univ of Utah Primary Children's Hospital
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University Of Virginia Hospitl
    • Norfolk, Virginia, United States, 23507
      • Children's Hsptl Of The Kings

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 6 years (Child)
• Accepts Healthy Volunteers: No

Description

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, age below 6 years of age at the time of signing informed consent
• Diagnosis of severe haemophilia A (FVIII activity level 1%) based on medical records or central laboratory results
• No prior use of purified clotting factor products (5 previous exposures to blood components is acceptable)

Exclusion Criteria:

• Any history of FVIII inhibitor (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 A
• 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')/legally acceptable representative (LAR(s')) mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation

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: 50 EDs (exposure days)	Drug: turoctocog alfa pegol; For intravenous (i.v.) injection. Frequency and dosage (20-75 U/kg) dependent on whether given as treatment for bleeding episode or as prophylaxis; Other Names: NNC 0129-0000-1003; N8-GP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII)	Number of participants with inhibitory antibodies against coagulation factor VIII (FVIII) was reported during the main and extension phase of the trial.	From start of the treatment up to 7 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events Including Serious Adverse Events and Medical Events of Special Interest	Number of adverse events including serious adverse events and medical events of special interest reported during the main and extension phase of the trial. An adverse event (AE) is any untoward medical occurrence in a patient administered a product, and which does not necessarily have a causal relationship with this treatment. Serious adverse event (SAE) is an experience that at any dose results in any of the following: Death, a life-threatening experience, in-patient hospitalisation or prolongation of existing hospitalisation, persistent or significant disability or incapacity, congenital anomaly or birth defect and important medical events that may not result in death, be life threatening or require hospitalisation. Medical event of special interest (MESI) is an event which, in the evaluation of safety, has a special focus.	From start of the treatment up to 8.9 years
Number of Participants With Confirmed High Titre Inhibitors (Defined as Inhibitor Titre Above 5 Bethesda Units (BU)	Number of participants with confirmed high titre inhibitors (defined as inhibitor titre above 5 Bethesda Units (BU) was reported during the main and extension phase of the trial.	From start of the treatment up to 8.9 years
Number of Breakthrough Bleeding Episodes During Prophylaxis With N8-GP (Annualised Bleeding Rate)	The number of bleeding episodes per year reported during the prophylactic treatment with N8-GP was reported.	From start of the treatment up to 8.9 years
Haemostatic Effect of N8-GP in Treatment of Bleeding Episodes, Assessed by a Predefined 4-point Haemostatic Response Scale ("Excellent", "Good", "Moderate" and "None")	Haemostatic effect of turoctocog alfa pegol for treatment of bleeding episodes was assessed by 4-point response scale: none, moderate, good or excellent. Excellent: Abrupt pain relief and/or clear improvement in objective signs of bleeding within approximately 8 hours after a single injection; Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after a single injection, but possibly requiring more than one injection for complete resolution; Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection, but usually requiring more than one injection; None: No improvement, or worsening of symptoms. Number of bleeding episodes in each category is reported.	From start of the treatment up to 8.9 years
Consumption of N8-GP for Prophylaxis (International Unit Per Kilogram (IU/Kg))	Consumption of N8-GP for prophylaxis is reported. Consumption used for treatment includes all doses given. Yearly consumption is only calculated for patients with a exposure time of at least 30 days. Average dose consumption in IU/kg during main and extension phase is reported.	From start of the treatment up to 8.9 years
Consumption of N8-GP for Prophylaxis (Number of Injections)	Consumption of N8-GP for prophylaxis is reported. Consumption used for treatment includes all doses given. Yearly consumption is only calculated for patients with a exposure time of at least 30 days. Number of injections consumption per patient during main and extension phase is reported.	From start of the treatment up to 8.9 years
Consumption of N8-GP for Treatment of Bleeding Episodes (International Unit Per Kilogram Per Bleed (IU/kg/Bleed))	Consumption of N8-GP for treatment of bleeding episodes (IU/kg/bleed) is reported. Average dose consumption in IU/kg/bleed during main and extension phase is reported.	From start of the treatment up to 8.9 years
Consumption of N8-GP for Treatment of Bleeding Episodes (Number of Injections)	Consumption of N8-GP for treatment of bleeding episodes (number of injections) is reported. Number of average injections required for treatment of per bleed is reported.	From start of the treatment up to 8.9 years
Total Consumption of N8-GP Per Patient (Prevention and Treatment of Bleeding Episodes) Annualised Value	Total consumption of N8-GP per patient (prevention and treatment of bleeding episodes) annualised value is presented. Consumption used for treatment includes all doses given. Yearly consumption is only calculated for patients with a exposure time of at least 30 days. Consumption used for treatment per year per patient (IU/kg/year/patient) is reported.	From start of the treatment up to 8.9 years
Outcome of ITI, Assessed by a Predefined 4-point ITI Outcome Scale ("Success", "Partial Success", "Failure", "Other")	The outcome of ITI was evaluated by predefined 4-point outcome of ITI scale ('success', 'partial success', 'failure', 'other'). Success: An inhibitor titre less than (<) 0.6 BU. A normalised FVIII recovery, defined as greater than or equal to (≥) 66 percentage (%) of expected incremental recovery. An N8-GP half-life (t½) ≥9 hours after a 72-hour treatment-free washout period. Partial success: Reduction in inhibitor titre to less than or equal to (≤) 5 BU. Clinical effect of N8-GP therapy as judged by the investigator. Failure: Failure to attain defined success or partial success within 24 months of uninterrupted ITI with N8-GP. Inhibitor decrease less than (<) 20% after one year of ITI treatment. Other: Not fulfilling the above criteria. Number of participants in each category is reported.	From start of the treatment up to 8.9 years

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Publications and helpful links

General Publications

• Kenet G, Young G, Chuansumrit A, Matsushita T, Yadav V, Zak M, Male C. The immunogenicity, safety, and efficacy of N8-GP in previously untreated patients with severe hemophilia A: pathfinder6 end-of-trial results. J Thromb Haemost. 2023 Nov;21(11):3109-3116. doi: 10.1016/j.jtha.2023.07.030. Epub 2023 Aug 18.
• Male C, Konigs C, Dey S, Matsushita T, Millner AH, Zak M, Young G, Kenet G. The safety and efficacy of N8-GP (turoctocog alfa pegol) in previously untreated pediatric patients with hemophilia A. Blood Adv. 2023 Feb 28;7(4):620-629. doi: 10.1182/bloodadvances.2022007529.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): June 26, 2014
• Primary Completion (Actual): June 7, 2023
• Study Completion (Actual): June 7, 2023

Study Registration Dates

• First Submitted: March 28, 2014
• First Submitted That Met QC Criteria: May 12, 2014
• First Posted (Estimated): May 14, 2014

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; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A
• Other Study ID Numbers: NN7088-3908; 2013-004025-88 (EudraCT Number); U1111-1148-1897 (Other Identifier: WHO); REec-2014-0898 (Registry Identifier: Spanish Register of Clinical Studies (REec)); JapicCTI-142577 (Other Identifier: JAPIC)