Clinical trial NCT01480180: Evaluation of Safety and Efficacy, Including Pharmacokinetics, of NNC 0129-0000-1003 When Administered for Treatment and Prophylaxis of Bleeding in Subjects With Haemophilia A
Official title: A Multi-national Trial Evaluating Safety and Efficacy, Including Pharmacokinetics, of NNC 0129-0000-1003 When Administered for Treatment and Prophylaxis of Bleeding in Patients With Haemophilia A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Congenital Bleeding Disorder
Haemophilia A
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2011-11-28
Enrollment: 186
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted globally. The aim of the trial is to evaluate the safety and efficacy, including pharmacokinetics (the exposure of the trial drug in the body) of NNC 0129-0000-1003 (N8-GP) in subjects with Haemophilia A.


Eligibility criteria: Inclusion Criteria: - Male patients with severe congenital haemophilia A (FVIII activity below 1%, according to medical records) - Documented history of at least 150 EDs (exposure days) to other FVIII products - At least 12 years and body weight at least 35 kg (except for Croatia, France, Russia, Israel and the Netherlands where the lower age limit will be 18 years) Exclusion Criteria: - Previous participation in this trial defined as withdrawal after administration N8-GP - Any history of FVIII inhibitors - FVIII inhibitors above or equal to 0.6 BU/mL at screening - HIV (human immunodeficiency virus) positive, defined by medical records with CD4+ (T-lymphocyte subtype) count below or equal to 200/mcL or a viral load of more than 400000 copies/mL. If the data is not available in medical records within last 6 months, CD4+ will be measured at the screening visit - Congenital or acquired coagulation disorders other than haemophilia A - Previous significant thromboembolic events (e.g. myocardial infarction, cerebrovascular disease or deep venous thrombosis) as defined by available medical records - Platelet count below 50,000 platelets/mcL (laboratory value at the screening visit) - ALAT (alanine aminotransferase) above 3 times the upper limit of normal reference ranges at central laboratory - Creatinine level equal to or greater than 1.5 times above upper normal limit (according to central laboratory reference ranges) - Ongoing immune modulating or chemotherapeutic medication

Primary outcomes:
measure: The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: The Incidence Rate of FVIII-inhibitors ≥0.6 BU: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Incidence Rate of FVIII-inhibitors ≥0.6 BU: At Approximately 80 Months
timeFrame: At approximately 80 months
measure: Annualised Bleeding Rate in the Prophylaxis Arm: After Approximately 80 Months
timeFrame: After approximately 80 months
Secondary outcomes:
measure: Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Haemostatic Effect of N8-GP When Used for Treatment of Bleeds, Assessed on a Four-point Scale for Haemostatic Response (Excellent, Good, Moderate and None): After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Consumption of N8-GP Per Bleeding Episode (Number of Infusions): After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Consumption of N8-GP Per Bleeding Episode (U/kg): After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Consumption of N8-GP (Number of Infusions) During Prophylaxis and On-demand Treatment: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Consumption of N8-GP (U/kg Per Month) During Prophylaxis and On-demand Treatment: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Consumption of N8-GP (U/kg Per Year) During Prophylaxis and On-demand Treatment: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Haemostatic Effect as Measured by Recovery and Trough Levels FVIII:C (in All Patients Receiving Prophylaxis Treatment): After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old) After Approx 19 and 25 Months
timeFrame: After approx 19 and 25 months
measure: Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Patients 13-16 Years Old): After Approx 80 Months
timeFrame: 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs
measure: Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 19 and 25 Months
timeFrame: After approx 19 and 25 months
measure: Patient Reported Outcomes - Change in HAEMO-QOL Total Scores (Parents of Patients 13-16 Years Old): After Approx 80 Months
timeFrame: 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs
measure: Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approx 19 and 25 Months
timeFrame: After approx 19 and 25 months
measure: Patient Reported Outcomes - Change in HAEM-A-QOL (>=17 Years) Total Scores: After Approximately 80 Months
timeFrame: 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs
measure: Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approx 19 and 25 Months
timeFrame: After approx 19 and 25 months
measure: Patient Reported Outcomes - Change in HEMO-SAT (Patients) Scores: After Approximately 80 Months
timeFrame: 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs
measure: Patient Reported Outcomes - Change in HEMO-SAT Scores (Parents): After Approx 19 and 25 Months
timeFrame: After approx 19 and 25 months
measure: Patient Reported Outcomes - Change in HEMO-SAT (Parents) Scores: After Approximately 80 Months
timeFrame: 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs
measure: Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approx 19 and 25 Months
timeFrame: After approx 19 and 25 months
measure: Patient Reported Outcomes - Change in EQ-5D-VAS Scores: After Approximately 80 Months
timeFrame: 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs
measure: Patient Reported Outcomes - Change in European Quality of Life Utility Index: After Approx 19 and 25 Months
timeFrame: After approx 19 and 25 months
measure: Patient Reported Outcomes - Change in European Quality of Life Utility Index Scores: After Approximately 80 Months
timeFrame: 1-<2 yrs, 2-<3 yrs, 3-<4 yrs, 4-<5 yrs, 5-<6 yrs and 6-<7 yrs
measure: Number of Hospital Admissions During the Trial
timeFrame: After approx 19, 25 and 80 months
measure: Number of Days at the Hospital During the Trial
timeFrame: After approx 19, 25 and 80 months
measure: Number of Admissions to the Emergency Room (ER) During the Trial
timeFrame: After approx 19, 25 and 80 months
measure: Number of Days Missing School or Work
timeFrame: Approx 19, 25 and 80 months
measure: Number of Days Using Mobility Aid
timeFrame: Approx 19, 25 and 80 months
measure: Number of Participants Using Pain Medication
timeFrame: After approx 25 and 80 months
measure: Number of Bleeds Using Pain Medication
timeFrame: After approx 19 months
measure: Number of Adverse Events Reported During the Trial Period: After Approximately 19 Months
timeFrame: After approx 19 months
measure: Number of Adverse Events Reported During the Trial Period: After Approximately 25 Months
timeFrame: After approx. 25 months
measure: Number of Adverse Events Reported During the Trial Period: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Number of Serious Adverse Events Reported During the Trial Period: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Number of Serious Adverse Events Reported During the Trial Period: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Number of Serious Adverse Events Reported During the Trial Period: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Change in Blood Pressure: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Change in Blood Pressure: After Approximately 25 Months
timeFrame: After approximately 19 and 25 months
measure: Change in Blood Pressure: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Change in Pulse: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Change in Pulse: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Change in Pulse: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Change in Body Temperature: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Change in Body Temperature: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Change in Body Temperature: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: Change in Respiratory Rate: After Approximately 19 Months
timeFrame: After approximately 19 months
measure: Change in Respiratory Rate: After Approximately 25 Months
timeFrame: After approximately 25 months
measure: Change in Respiratory Rate: After Approximately 80 Months
timeFrame: After approximately 80 months
measure: FVIII Activity 30 Min Post -Injection (C30min)
timeFrame: Week 0, week 28
measure: Incremental Recovery (Single Dose and Steady State)
timeFrame: Week 0, week 28
measure: Trough Level (Single Dose and Steady State)
timeFrame: Week 0, week 28
measure: Area Under the Curve (AUC0-inf)
timeFrame: Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28
measure: Area Under the Curve (AUC0-t)
timeFrame: Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28
measure: Terminal Half Life (t1/2)
timeFrame: Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28
measure: Clearance (CL)
timeFrame: Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28
measure: Mean Residence Time (MRT)
timeFrame: Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Pre dose and 30 min, 1, 4, 12, 24, 48, 72 and 96 hours post dose at week 0 and week 28
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Long Beach
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Sacramento
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Torrance
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Washington
country: United States
facility: Novo Nordisk Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: Novo Nordisk Investigational Site
state: District of Columbia
city: Orlando
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Tampa
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Augusta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Boise
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Iowa City
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: New Orleans
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Boston
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: East Lansing
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Omaha
country: United States
facility: Novo Nordisk Investigational Site
state: Nebraska
city: New Brunswick
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Newark
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Portland
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Charlottesville
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Norfolk
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Spokane
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Camperdown
country: Australia
facility: Novo Nordisk Investigational Site
state: New South Wales
city: South Brisbane
country: Australia
facility: Novo Nordisk Investigational Site
state: Queensland
city: Parkville
country: Australia
facility: Novo Nordisk Investigational Site
state: Victoria
city: Campinas
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: Sofia
country: Bulgaria
facility: Novo Nordisk Investigational Site
city: Split
country: Croatia
facility: Novo Nordisk Investigational Site
city: Zagreb
country: Croatia
facility: Novo Nordisk Investigational Site
city: København Ø
country: Denmark
facility: Novo Nordisk Investigational Site
city: Århus N
country: Denmark
facility: Novo Nordisk Investigational Site
city: Bron Cedex
country: France
facility: Novo Nordisk Investigational Site
city: Kremlin-Bicêtre
country: France
facility: Novo Nordisk Investigational Site
city: Nantes Cedex 1
country: France
facility: Novo Nordisk Investigational Site
city: Paris
country: France
facility: Novo Nordisk Investigational Site
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
city: Bonn
country: Germany
facility: Novo Nordisk Investigational Site
city: Frankfurt/M.
country: Germany
facility: Novo Nordisk Investigational Site
city: Hannover
country: Germany
facility: Novo Nordisk Investigational Site
city: Homburg
country: Germany
facility: Novo Nordisk Investigational Site
city: München
country: Germany
facility: Novo Nordisk Investigational Site
city: Budapest
country: Hungary
facility: Novo Nordisk Investigational Site
city: Debrecen
country: Hungary
facility: Novo Nordisk Investigational Site
city: Tel-Hashomer
country: Israel
facility: Novo Nordisk Investigational Site
city: Firenze
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Udine
country: Italy
facility: Novo Nordisk Investigational Site
city: Vicenza
country: Italy
facility: Novo Nordisk Investigational Site
city: Aichi
country: Japan
facility: Novo Nordisk Investigational Site
city: Hiroshima
country: Japan
facility: Novo Nordisk Investigational Site
city: Kitakyusyu, Fukuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Nara
country: Japan
facility: Novo Nordisk Investigational Site
city: Saitama
country: Japan
facility: Novo Nordisk Investigational Site
city: Shimotsuke-shi, Tochigi
country: Japan
facility: Novo Nordisk Investigational Site
city: Shizuoka
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Yokohama-shi, Kanagawa
country: Japan
facility: Novo Nordisk Investigational Site
city: Daejeon
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Selangor Darul Ehsan
country: Malaysia
facility: Novo Nordisk Investigational Site
city: Groningen
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Rotterdam
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Oslo
country: Norway
facility: Novo Nordisk Investigational Site
city: San Juan
country: Puerto Rico
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Madrid
country: Spain
facility: Novo Nordisk Investigational Site
city: Málaga
country: Spain
facility: Novo Nordisk Investigational Site
city: Malmö
country: Sweden
facility: Novo Nordisk Investigational Site
city: Genève 14
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Lausanne
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Zürich
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Changhua
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Adana
country: Turkey
facility: Novo Nordisk Investigational Site
city: Bornova-IZMIR
country: Turkey
facility: Novo Nordisk Investigational Site
city: Samsun
country: Turkey
facility: Novo Nordisk Investigational Site
city: Basingstoke
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Cardiff
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: London
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Oxford
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Sheffield
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Giangrande P, Chowdary P, Enhrenforth S, Hanabusa H, Leebeek FW, Lentz SR, Nemes L, Poulsen LH, Santagostino E, You CW, Clausen WHO, Oldenburg J and on behalf of for the pathfinder™2 Investigators. Clinical evaluation of novel recombinant glycopegylated FVIII (turoctocog alfa pegol, N8-GP): efficacy and safety in previously treated patients with severe hemophilia A - results of pathfinder™2 international trial. Journal of Thrombosis and Haemostasis (Abstracts) 2015; 13 (Supplement S2): 1-997 [OR212]
citation: Giangrande P, Andreeva T, Chowdary P, Ehrenforth S, Hanabusa H, Leebeek FW, Lentz SR, Nemes L, Poulsen LH, Santagostino E, You CW, Clausen WH, Jonsson PG, Oldenburg J; Pathfinder2 Investigators. Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A. Thromb Haemost. 2017 Jan 26;117(2):252-261. doi: 10.1160/TH16-06-0444. Epub 2016 Dec 1.
citation: Giangrande P, Abdul Karim F, Nemes L, You CW, Landorph A, Geybels MS, Curry N. Long-term safety and efficacy of N8-GP in previously treated adults and adolescents with hemophilia A: Final results from pathfinder2. J Thromb Haemost. 2020 Sep;18 Suppl 1(Suppl 1):5-14. doi: 10.1111/jth.14959.