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

• ClinicalTrials.gov Identifier: NCT03528551
• Recruitment Status: Completed
• First Posted: May 18, 2018
• Results First Posted: November 26, 2021
• Last Update Posted: December 22, 2022
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Tracking Information

• First Submitted Date: April 18, 2018
• First Posted Date: May 18, 2018
• Results First Submitted Date: July 22, 2021
• Results First Posted Date: November 26, 2021
• Last Update Posted Date: December 22, 2022
• Actual Study Start Date: April 30, 2018
• Actual Primary Completion Date: December 3, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 22, 2021)

Number of Adverse Events Reported [ Time Frame: Week 0 to week 108 ]

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).

Original Primary Outcome Measures (submitted: May 15, 2018)

Number of adverse events reported [ Time Frame: Weeks 0-104 ]

Count of adverse events

Current Secondary Outcome Measures (submitted: September 9, 2021)

• Number of Participants With Inhibitory Antibodies Against Coagulation Factor VIII (FVIII) ≥0.6 Bethesda Units (BU) [ Time Frame: Week 0 to week 104 ]
  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.
• Number of Bleeding Episodes on Prophylaxis [ Time Frame: Week 0 to week 104 ]
  Number of bleeding episodes per participant in the prophylaxis regimen was evaluated during 104 weeks.
• Number of Spontaneous Bleeding Episodes on Prophylaxis [ Time Frame: Week 0 to week 104 ]
  Spontaneous bleeding referred as bleeding episodes that occurred without apparent cause. The number of spontaneous bleeding episodes were evaluated during 104 weeks.
• Haemostatic Effect of N8-GP When Used for Treatment of Bleeding Episodes Assessed as: Excellent, Good, Moderate, or None [ Time Frame: Week 0 to week 104 ]
  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.
• Mean Number of N8-GP Injections Required Per Bleeding Episode [ Time Frame: Week 0 to week 104 ]
  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.
• Pre-dose FVIII Activity Levels on N8-GP Prophylaxis [ Time Frame: Week 0 to week 104 ]
  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.
• Change in Joint Health Status From Start to End of Trial (Based on Haemophilia Joint Health Score) [ Time Frame: Week 0, Week 104 ]
  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.
• Haemostatic Response During Major Surgical Interventions Assessed as: Excellent, Good, Moderate, or None [ Time Frame: Week 0 to week 104 ]
  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.
• Consumption of N8-GP Per Bleed [ Time Frame: Week 0 to week 104 ]
  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.
• Consumption of N8-GP During Prophylaxis Treatment [ Time Frame: Week 0 to week 104 ]
  The average dose of N8-GP consumed for prevention of bleed was assessed. This endpoint was evaluated from week 0 to week 104.
• Change From Start Till End of Trial in Treatment Satisfaction (Based on Hemo-SAT Score) [ Time Frame: Week 0, Week 104 ]
  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.

Original Secondary Outcome Measures (submitted: May 15, 2018)

• Incidence of FVIII inhibitors ≥0.6 BU [ Time Frame: Weeks 0-104 ]
  Count of presence of inhibitors
• Number of bleeding episodes on prophylaxis [ Time Frame: Weeks 0-104 ]
  Count of episodes
• Number of spontaneous bleeding episodes on prophylaxis [ Time Frame: Weeks 0-104 ]
  Count of episodes
• Haemostatic effect of N8-GP when used for treatment of bleeding episodes assessed as: Excellent, Good, Moderate, or None [ Time Frame: Weeks 0-104 ]
  Assessed as: Excellent, good, moderate, or none
• Number of N8-GP injections required per bleeding episode [ Time Frame: Weeks 0-104 ]
  Number of injections
• Pre-dose FVIII activity levels on N8-GP prophylaxis (IU/dL) [ Time Frame: Weeks 0-104 ]
  Calculated based on plasma FVIII activity measured in blood
• Change in joint health status from start to end of trial (based on Haemophilia Joint Health Score) [ Time Frame: Week 0, Week 104 ]
  Based on Haemophilia Joint Health Score
• Haemostatic response during major surgical interventions assessed as: Excellent, Good, Moderate, or None [ Time Frame: Weeks 0-104 ]
  Assessed as: Excellent, good, moderate, or none
• Consumption of N8-GP per bleed [ Time Frame: Weeks 0-104 ]
  Number of infusions and IU/kg per bleed
• Consumption of N8-GP during prophylaxis treatment [ Time Frame: Weeks 0-104 ]
  Number of infusions and IU/kg per month and per year
• Change from start till end of trial in treatment satisfaction (based on Hemo-SAT score) [ Time Frame: Week 0, Week 104 ]
  Based on Haemophilia Satisfaction Survey (Hemo-SAT) score

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Research Study Looking at How a Factor VIII Medicine Called Turoctocog Alfa Pegol (N8-GP) Works in People With Haemophilia A
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Congenital Bleeding Disorder
• Haemophilia A

Intervention

• 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.

Study Arms

• Experimental: N8-GP, once weekly
  All participants will receive turoctocog alfa pegol (N8-GP) once weekly.
  Intervention: Drug: Turoctocog alfa pegol
• Experimental: N8-GP, twice weekly
  All participants will receive N8-GP twice weekly.
  Intervention: Drug: Turoctocog alfa pegol
• Experimental: N8-GP, three times weekly
  All participants will receive N8-GP three times weekly.
  Intervention: Drug: Turoctocog alfa pegol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 21, 2019): 160
• Original Estimated Enrollment (submitted: May 15, 2018): 173
• Actual Study Completion Date: December 3, 2020
• Actual Primary Completion Date: December 3, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Canada, Croatia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Lithuania, Malaysia, Netherlands, Norway, Portugal, Puerto Rico, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT03528551
• 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 )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
• URL: http://novonordisk-trials.com

• Current Responsible Party: Novo Nordisk A/S
• Original Responsible Party: Same as current
• Current Study Sponsor: Novo Nordisk A/S
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure 2834; Novo Nordisk A/S

• PRS Account: Novo Nordisk A/S
• Verification Date: December 2022