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

Congenital Bleeding Disorder Clinical Trial

— pathfinder8  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03528551
• Other study ID #: NN7088-4410
• Secondary ID: U1111-1202-27802
• Status: Completed
• Phase: Phase 3
• Start date: April 30, 2018
• Est. completion date: December 3, 2020

Study information

• Verified date: December 2022
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: December 3, 2020
• Est. primary completion date: December 3, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Congenital Bleeding Disorder
• Haemophilia A
• Hemophilia A
• Hemostatic Disorders

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.
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Novo Nordisk Investigational Site	Camperdown	New South Wales
Australia	Novo Nordisk Investigational Site	Parkville	Victoria
Brazil	Novo Nordisk Investigational Site	Campinas	Sao Paulo
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Croatia	Novo Nordisk Investigational Site	Zagreb
Denmark	Novo Nordisk Investigational Site	Århus N
France	Novo Nordisk Investigational Site	Bron Cedex
France	Novo Nordisk Investigational Site	Le Kremlin Bicetre
France	Novo Nordisk Investigational Site	Nantes Cedex 1
Germany	Novo Nordisk Investigational Site	Berlin
Germany	Novo Nordisk Investigational Site	Frankfurt/M.
Germany	Novo Nordisk Investigational Site	Homburg
Greece	Novo Nordisk Investigational Site	Athens
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Debrecen
Israel	Novo Nordisk Investigational Site	Tel-Hashomer
Italy	Novo Nordisk Investigational Site	Milano
Italy	Novo Nordisk Investigational Site	Vicenza
Japan	Novo Nordisk Investigational Site	Kitakyusyu-shi, Fukuoka
Japan	Novo Nordisk Investigational Site	Nara
Japan	Novo Nordisk Investigational Site	Tokyo
Korea, Republic of	Novo Nordisk Investigational Site	Daejeon
Lithuania	Novo Nordisk Investigational Site	Vilnius
Malaysia	Novo Nordisk Investigational Site	Selangor Darul Ehsan
Netherlands	Novo Nordisk Investigational Site	Groningen
Netherlands	Novo Nordisk Investigational Site	Rotterdam
Norway	Novo Nordisk Investigational Site	Oslo
Portugal	Novo Nordisk Investigational Site	Porto
Puerto Rico	Novo Nordisk Investigational Site	San Juan
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Málaga
Switzerland	Novo Nordisk Investigational Site	Bellinzona
Switzerland	Novo Nordisk Investigational Site	Lausanne
Switzerland	Novo Nordisk Investigational Site	Zürich
Switzerland	Novo Nordisk Investigational Site	Zürich
Taiwan	Novo Nordisk Investigational Site	Taipei
Turkey	Novo Nordisk Investigational Site	Adana
Turkey	Novo Nordisk Investigational Site	Antalya
Turkey	Novo Nordisk Investigational Site	Bornova-IZMIR
Turkey	Novo Nordisk Investigational Site	Izmit
Turkey	Novo Nordisk Investigational Site	Samsun
Ukraine	Novo Nordisk Investigational Site	Lviv
United Kingdom	Novo Nordisk Investigational Site	Basingstoke
United Kingdom	Novo Nordisk Investigational Site	Cardiff
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Oxford
United Kingdom	Novo Nordisk Investigational Site	Oxford
United Kingdom	Novo Nordisk Investigational Site	Sheffield
United States	Novo Nordisk Investigational Site	Baltimore	Maryland
United States	Novo Nordisk Investigational Site	Charleston	South Carolina
United States	Novo Nordisk Investigational Site	Charlotte	North Carolina
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	Detroit	Michigan
United States	Novo Nordisk Investigational Site	East Lansing	Michigan
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Iowa City	Iowa
United States	Novo Nordisk Investigational Site	Long Beach	California
United States	Novo Nordisk Investigational Site	Minneapolis	Minnesota
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	New Hyde Park	New York
United States	Novo Nordisk Investigational Site	New Orleans	Louisiana
United States	Novo Nordisk Investigational Site	Norfolk	Virginia
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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