A Research Study Looking at How a Factor VIII Medicine Called Turoctocog Alfa Pegol (N8-GP) Works in People With Haemophilia A (pathfinder8)

Safety and Efficacy of Turoctocog Alfa Pegol (N8-GP) in Prophylaxis and Treatment of Bleeds in Previously N8-GP Treated Patients With Severe Haemophilia A

This study will look at how a known study medicine N8-GP works in previously N8-GP treated people with haemophilia A. The aim is to look at how N8-GP works during regular use. Participants will get N8-GP. N8-GP has been tested in more than 200 people with haemophilia A for several years. Participants will get an injection of N8-GP into a blood vessel, one, two or three times weekly. Participants will get more doses if they bleed or if they will need a surgery. The study will last for about 2 years. Participants will have at least 9 visits with the study doctor. If participants agree to be in this study, they will get their first injection (in this study) at the first visit. Participants will also get an injection at visit 3, 5 and 7. Participants will be trained to give all other injections themselves. Participants must not use any clotting factors other than N8-GP or any anticoagulants (blood thinners) during the study.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Novo Nordisk Investigational Site
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Novo Nordisk Investigational Site
• Brazil
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13081-970
      • Novo Nordisk Investigational Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • Novo Nordisk Investigational Site
• Croatia
  • Zagreb, Croatia, 10 000
    • Novo Nordisk Investigational Site
• Denmark
  • Århus N, Denmark, 8200
    • Novo Nordisk Investigational Site
• France
  • Bron Cedex, France, 69677
    • Novo Nordisk Investigational Site
  • Le Kremlin Bicetre, France, 94270
    • Novo Nordisk Investigational Site
  • Nantes Cedex 1, France, 44093
    • Novo Nordisk Investigational Site
• Germany
  • Berlin, Germany, 10249
    • Novo Nordisk Investigational Site
  • Frankfurt/M., Germany, 60590
    • Novo Nordisk Investigational Site
  • Homburg, Germany, 66421
    • Novo Nordisk Investigational Site
• Greece
  • Athens, Greece, GR-11527
    • Novo Nordisk Investigational Site
• Hungary
  • Budapest, Hungary, H-1134
    • Novo Nordisk Investigational Site
  • Debrecen, Hungary, 4012
    • Novo Nordisk Investigational Site
• Israel
  • Tel-Hashomer, Israel, 52621
    • Novo Nordisk Investigational Site
• Italy
  • Milano, Italy, 20124
    • Novo Nordisk Investigational Site
  • Vicenza, Italy, 36100
    • Novo Nordisk Investigational Site
• Japan
  • Kitakyusyu-shi, Fukuoka, Japan, 807 8555
    • Novo Nordisk Investigational Site
  • Nara, Japan, 634-8522
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 167-0035
    • Novo Nordisk Investigational Site
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35233
    • Novo Nordisk Investigational Site
• Lithuania
  • Vilnius, Lithuania, 08406
    • Novo Nordisk Investigational Site
• Malaysia
  • Selangor Darul Ehsan, Malaysia, 68000
    • Novo Nordisk Investigational Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Novo Nordisk Investigational Site
  • Rotterdam, Netherlands, 3015 CE
    • Novo Nordisk Investigational Site
• Norway
  • Oslo, Norway, 0027
    • Novo Nordisk Investigational Site
• Portugal
  • Porto, Portugal, 4200-319
    • Novo Nordisk Investigational Site
• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • Novo Nordisk Investigational Site
• Spain
  • Madrid, Spain, 28046
    • Novo Nordisk Investigational Site
  • Málaga, Spain, 29010
    • Novo Nordisk Investigational Site
• Switzerland
  • Bellinzona, Switzerland, 6500
    • Novo Nordisk Investigational Site
  • Lausanne, Switzerland, 1011
    • Novo Nordisk Investigational Site
  • Zürich, Switzerland, 8091
    • Novo Nordisk Investigational Site
  • Zürich, Switzerland, 8032
    • Novo Nordisk Investigational Site
• Taiwan
  • Taipei, Taiwan, 100
    • Novo Nordisk Investigational Site
• Turkey
  • Adana, Turkey, 01130
    • Novo Nordisk Investigational Site
  • Antalya, Turkey, 01010
    • Novo Nordisk Investigational Site
  • Bornova-IZMIR, Turkey, 35100
    • Novo Nordisk Investigational Site
  • Izmit, Turkey, 41380
    • Novo Nordisk Investigational Site
  • Samsun, Turkey, 55139
    • Novo Nordisk Investigational Site
• Ukraine
  • Lviv, Ukraine, 79044
    • Novo Nordisk Investigational Site
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9NA
    • Novo Nordisk Investigational Site
  • Cardiff, United Kingdom, CF14 4XW
    • Novo Nordisk Investigational Site
  • London, United Kingdom, NW3 2QG
    • Novo Nordisk Investigational Site
  • London, United Kingdom, SE1 7EH
    • Novo Nordisk Investigational Site
  • Oxford, United Kingdom, OX3 9DU
    • Novo Nordisk Investigational Site
  • Oxford, United Kingdom, OX3 7LJ
    • Novo Nordisk Investigational Site
  • Sheffield, United Kingdom, S10 2JF
    • Novo Nordisk Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Novo Nordisk Investigational Site
  • California
    • Long Beach, California, United States, 90806
      • Novo Nordisk Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Novo Nordisk Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70118-5720
      • Novo Nordisk Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Novo Nordisk Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Novo Nordisk Investigational Site
    • East Lansing, Michigan, United States, 48824
      • Novo Nordisk Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Novo Nordisk Investigational Site
  • New York
    • New Hyde Park, New York, United States, 11040
      • Novo Nordisk Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Novo Nordisk Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Novo Nordisk Investigational Site
    • Dayton, Ohio, United States, 45404
      • Novo Nordisk Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Novo Nordisk Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Novo Nordisk Investigational Site
  • Tennessee
    • Nashville, Tennessee, United States, 37232-9830
      • Novo Nordisk Investigational Site
  • Texas
    • Houston, Texas, United States, 77030
      • Novo Nordisk Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male patients of all ages with the diagnosis of severe congenital haemophilia A (coagulation Factor VIII [FVIII] activity less than 1%) based on medical records
• On-going participation in NN7088-3859 (pathfinder2), or NN7088-3885 (pathfinder5) at the time of transfer

Exclusion Criteria:

• Known or suspected hypersensitivity to trial product including allergy to hamster protein or related products
• Any disorder, except for conditions associated with haemophilia, which in the investigator's opinion might jeopardise patient's safety or compliance with the protocol - Current participation in any clinical trial (except NN7088-3859 (pathfinder2) or NN7088-3885 (pathfinder5)) of an approved or non-approved investigational medicinal product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N8-GP, once weekly; All participants will receive turoctocog alfa pegol (N8-GP) once weekly.	Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 75 IU/kg body weight will be administered once weekly as intravenous injections for a duration of 2 years.; Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 60 IU/kg body weight (for patients younger than 12 years) and 50 IU/kg body weight (for patients, 12 years or older) will be administered twice weekly as intravenous injections for a duration of 2 years.; Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 50 IU/kg body weight will be administered three times weekly as intravenous injections for a duration of 2 years.
Experimental: N8-GP, twice weekly; All participants will receive N8-GP twice weekly.	Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 75 IU/kg body weight will be administered once weekly as intravenous injections for a duration of 2 years.; Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 60 IU/kg body weight (for patients younger than 12 years) and 50 IU/kg body weight (for patients, 12 years or older) will be administered twice weekly as intravenous injections for a duration of 2 years.; Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 50 IU/kg body weight will be administered three times weekly as intravenous injections for a duration of 2 years.
Experimental: N8-GP, three times weekly; All participants will receive N8-GP three times weekly.	Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 75 IU/kg body weight will be administered once weekly as intravenous injections for a duration of 2 years.; Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 60 IU/kg body weight (for patients younger than 12 years) and 50 IU/kg body weight (for patients, 12 years or older) will be administered twice weekly as intravenous injections for a duration of 2 years.; Drug: Turoctocog alfa pegol; Turoctocog alfa pegol 50 IU/kg body weight will be administered three times weekly as intravenous injections for a duration of 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events Reported	An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAEs). The TEAE is defined as an event reported from date of first trial product administration until end of the treatment visit (week 104) or follow-up visit if relevant (1 month after end of the treatment).	Week 0 to week 108

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units (BU)	The Incidence of inhibitors against coagulation factor eight (FVIII) is defined as titre greater than or equal to (≥) 0.6 Bethesda unit. The inhibitor antibodies were measured using a heat modified Nijmegen FVIII Bethesda assay. The number of participants who developed inhibitors against FVIII are reported.	Week 0 to week 104
Number of Bleeding Episodes on Prophylaxis	Number of bleeding episodes per participant in the prophylaxis regimen was evaluated during 104 weeks.	Week 0 to week 104
Number of Spontaneous Bleeding Episodes on Prophylaxis	Spontaneous bleeding referred as bleeding episodes that occurred without apparent cause. The number of spontaneous bleeding episodes were evaluated during 104 weeks.	Week 0 to week 104
Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes Assessed as: Excellent, Good, Moderate, or None	The haemostatic effect after treatment of a bleed with N8-GP was assessed using a 4-point scale: 'excellent', 'good', 'moderate' or 'none'. The evaluation was done as follows: 1. Excellent: Abrupt pain relief and/or unequivocal improvement in objective signs of bleeding within approximately 8 hours after a single injection. 2. Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after an injection, but possibly requiring more than one injection for complete resolution. 3. Moderate: Probable or slight beneficial effect within approximately 8 hours after the first injection; usually requiring more than one injection 4. None: No improvement or worsening of symptoms.	Week 0 to week 104
Mean Number of N8-GP Injections Required Per Bleeding Episode	The mean number of N8-GP injections required per bleeding episode from start to stop of a bleed for participants was presented from week 0 to week 104.	Week 0 to week 104
Pre-dose FVIII Activity Levels on N8-GP Prophylaxis	The pre-dose FVIII activity levels were assessed in International units per millilitre (IU/mL) units from week 0 to week 104 to get an estimate of the pre-dose level for N8-GP at steady-state using mixed model.	Week 0 to week 104
Change in Joint Health Status From Start to End of Trial (Based on Haemophilia Joint Health Score)	Haemophilia Joint Health Score is a validated outcome tool developed for the assessment of joint health in patients with hemophilia. It comprises an evaluation of the elbow, knee and ankle joints with regards to swelling, muscular atrophy, crepitation and range of motion, joint pain, strength, motion and axial alignment. The score range is from 0 to 24 points (a score of 0 indicates no joint damage. Higher the score higher the joint damage). Change from week 0 to end of trial (week 104) in the domain scores was presented.	Week 0, Week 104
Haemostatic Response During Major Surgical Interventions Assessed as: Excellent, Good, Moderate, or None	The Haemostatic response to N8-GP during major surgical interventions was assessed using a 4-point scale: 'excellent', 'good', 'moderate' or 'none'. The evaluation was done as follows: 1. Excellent: Better than expected/predicted in this type of procedure. 2. Good: As expected in this type of procedure 3. Moderate: Less than optimal for the type of procedure but haemostatic response maintained without change of treatment regimen 4. None: Bleeding due to inadequate therapeutic response with adequate dosing, change of regimen required. This endpoint was measured from week 0 to week 104.	Week 0 to week 104
Consumption of N8-GP Per Bleed	The average dose of N8-GP consumed for treatment of bleed was assessed in International units per kilogram per bleed(IU/kg/bleed). This endpoint was evaluated from week 0 to week 104.	Week 0 to week 104
Consumption of N8-GP During Prophylaxis Treatment	The average dose of N8-GP consumed for prevention of bleed was assessed. This endpoint was evaluated from week 0 to week 104.	Week 0 to week 104
Change From Start Till End of Trial in Treatment Satisfaction (Based on Hemo-SAT Score)	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), with a scale of 0-100. The lower scores reflecting greater treatment satisfaction. In other words, decrease in the score would mean improvement. The summary of change presented was based on individual changes since week 0. Data is presented for total score.	Week 0, Week 104

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Reporting Anchor and Disclosure 2834, Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2018
• Primary Completion (Actual): December 3, 2020
• Study Completion (Actual): December 3, 2020

Study Registration Dates

• First Submitted: April 18, 2018
• First Submitted That Met QC Criteria: May 15, 2018
• First Posted (Actual): May 18, 2018

Study Record Updates

• Last Update Posted (Estimate): December 22, 2022
• Last Update Submitted That Met QC Criteria: December 20, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Hemostatic Disorders; Hemophilia A; Blood Coagulation Disorders; Coagulants; Factor VIII
• Other Study ID Numbers: NN7088-4410; U1111-1202-2780 (Other Identifier: World Health Organization (WHO)); 2017-003788-36 (Registry Identifier: European Medicines Agency (EudraCT)); JapicCTI-183952 (Registry Identifier: JAPIC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: According to the Novo Nordisk disclosure 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