Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Previously Untreated Children With Haemophilia A (guardian™4)

Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Paediatric Previously Untreated Patients With Haemophilia A

This trial is conducted in Asia, Europe and North America. The purpose of the trial is to evaluate the safety and efficacy of turoctocog alfa in prevention and treatment of bleeds in previously untreated children with haemophilia A.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Algeria
  • Algiers, Algeria, 16000
    • Novo Nordisk Investigational Site
  • Annaba, Algeria, 23000
    • Novo Nordisk Investigational Site
• Austria
  • Graz, Austria, 8036
    • Novo Nordisk Investigational Site
  • Innsbruck, Austria, 6020
    • Novo Nordisk Investigational Site
  • Klagenfurt, Austria, A 9026
    • Novo Nordisk Investigational Site
  • Linz, Austria, 4020
    • Novo Nordisk Investigational Site
  • Salzburg, Austria, A 5020
    • Novo Nordisk Investigational Site
  • St. Poelten, Austria, A 3100
    • Novo Nordisk Investigational Site
  • Wien, Austria, A 1090
    • Novo Nordisk Investigational Site
• Brazil
  • Parana
    • Curitiba, Parana, Brazil, 80250-060
      • Novo Nordisk Investigational Site
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13081-970
      • Novo Nordisk Investigational Site
• China
  • Beijing, China, 100032
    • Novo Nordisk Investigational Site
  • Beijing
    • Beijing, Beijing, China, 100045
      • Novo Nordisk Investigational Site
  • Chongqing
    • Chonqqing, Chongqing, China, 400014
      • Novo Nordisk Investigational Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Novo Nordisk Investigational Site
  • Tianjin
    • Tianjing, Tianjin, China, 300020
      • Novo Nordisk Investigational Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Novo Nordisk Investigational Site
• Denmark
  • København Ø, Denmark, 2100
    • Novo Nordisk Investigational Site
• Greece
  • Athens, Greece, GR-11527
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR 54642
    • Novo Nordisk Investigational Site
• Hong Kong
  • Shatin, New Territories, Hong Kong
    • Novo Nordisk Investigational Site
• Hungary
  • Budapest, Hungary, 1089
    • Novo Nordisk Investigational Site
  • Debrecen, Hungary, 4032
    • Novo Nordisk Investigational Site
• Japan
  • Aichi, Japan, 466-8560
    • Novo Nordisk Investigational Site
  • Hyogo, Japan, 654-0047
    • Novo Nordisk Investigational Site
  • Shizuoka, Japan, 420-8660
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 157-8535
    • Novo Nordisk Investigational Site
• Lithuania
  • Vilnius, Lithuania, 08406
    • Novo Nordisk Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-094
    • Novo Nordisk Investigational Site
  • Lublin, Poland, 20-093
    • Novo Nordisk Investigational Site
• Portugal
  • Porto, Portugal, 4200-319
    • Novo Nordisk Investigational Site
• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • Novo Nordisk Investigational Site
• Russian Federation
  • Krasnodar, Russian Federation, 350007
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 119049
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 191065
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11070
    • Novo Nordisk Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • Novo Nordisk Investigational Site
  • El Palmar, Spain, 30120
    • Novo Nordisk Investigational Site
  • Madrid, Spain, 28046
    • 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, 55319
    • 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
    • Sacramento, California, United States, 95817
      • Novo Nordisk Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2978
      • Novo Nordisk Investigational Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Novo Nordisk Investigational Site
    • Orlando, Florida, United States, 32827
      • Novo Nordisk Investigational Site
    • Tampa, Florida, United States, 33607
      • Novo Nordisk Investigational Site
    • Tampa, Florida, United States, 33606
      • Novo Nordisk Investigational Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Novo Nordisk Investigational Site
    • Macon, Georgia, United States, 31201
      • Novo Nordisk Investigational Site
    • Savannah, Georgia, United States, 31404
      • Novo Nordisk Investigational Site
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Novo Nordisk Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Novo Nordisk Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Novo Nordisk Investigational Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Novo Nordisk Investigational Site
  • New York
    • Brooklyn, New York, United States, 11220
      • Novo Nordisk Investigational Site
    • Brooklyn, New York, United States, 11201-5425
      • 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
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novo Nordisk Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Novo Nordisk Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Novo Nordisk Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Novo Nordisk Investigational Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age below 6 years
• Informed consent obtained before any trial-related activities (trial-related activities are any procedure that would not have been performed during normal management of the patient)
• Male patients diagnosed with congenital severe haemophilia A (FVIII level equal to or below 1%)
• No prior use of purified clotting factor products (previous exposure, equal to or less than 5 ED to blood components, e.g. cryoprecipitate, fresh frozen plasma, is accepted) including commercially available NovoEight® /Novoeight®

Exclusion Criteria:

• Known or suspected allergy to hamster protein or intolerance to trial product(s) or related products
• Previous participation in this trial defined as withdrawal after administration of trial product
• Congenital or acquired coagulation disorders other than haemophilia A
• Any history of Factor VIII inhibitor
• Ongoing treatment or planned treatment during the trial with immunomodulatory agents (e.g. intravenous immunoglobulin (IVIG), routine systemic corticosteroids)

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: turoctocog alfa	Drug: turoctocog alfa; Patients will be scheduled to receive treatment with turoctocog alfa for at least 100 exposure days. In most cases, treatment will be given at home with intravenous (i.v., into the vein) self-injection by the parent/caregiver/support person.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence Rate of Factor VIII Inhibitors (Above or Equal to 0.6 BU (Bethesda Units)/mL) for the Main Phase of the Trial	The incidence rate (percentage of participants with inhibitors) of inhibitors defined as inhibitor titres ≥0.6 BU for main phase of the trial.	From Visit 2 (21 days after screening) to Visit 5 (50-55 exposure day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None	The haemostatic effect of turoctocog alfa was summarised by frequency tables containing count of all bleeds and assessed on a predefined four point scale: Excellent, Good, Moderate and None. The analysis was based on the total number of bleeds and their response to treatment. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Annualised Bleeding Rate (ABR)	Annualised bleeding rate defined as number of bleeds in total per patient per year following treatment were estimated by a Poisson model allowing for over-dispersion. The Poisson estimate is presented with a 95% confidence interval (CI). The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Number of Turoctocog Alfa (N8) Injections Required Per Bleed	The number of injections of turoctocog alfa (N8) required per bleed was calculated as the number of injections of turoctocog alfa used in the time period from start of the bleed to stop of the bleed. The mean number of turoctocog alfa injections required to stop the bleed is presented. The analysis was based on the total number of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month	Mean total consumption of turoctocog alfa (N8) used for treatment (includes all injections given: prevention, treatment of bleeds and during surgery) per patient per month. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year	Mean total consumption of turoctocog alfa (N8) used for treatment (includes all injections given: prevention, treatment of bleeds and during surgery) per patient per year. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed	Mean consumption of turoctocog alfa (N8) used for treatment of bleed from start to stop of bleed. The analysis was based on number of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention	Mean consumption of turoctocog alfa (N8) used for preventive treatment per month per patient. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period	Number of adverse events and serious adverse events per patient years of exposure. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial (exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level)	The incidence rates (number of patients with new inhibitor in the period/number of participants at risk, expressed in percentage) of clinically relevant inhibitors were defined as an inhibitor titre (≥ 0.6 BU) combined with a decreased recovery (<66% of expected level). Incidence rate of clinically relevant inhibitors according to the type of assay used is presented. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation) and the combined main and extension phase (from Visit 2 to end of trial).	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL)	Incidence rate (number of patients with new inhibitor in the period/number of participants at risk, expressed in percentage) of high-titre inhibitors defined as inhibitor titre ≥ 5 BU (Bethesda Units)/mL). The inhibitors were evaluated for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation) and the combined main and extension phase (from Visit 2 to end of trial).	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Change in Total Scores for Parent Reported Treatment Satisfaction	The caregivers/parent reported treatment satisfaction is assessed by the parents using the haemophilia satisfaction questionnaire (HEMO-SAT). The questionnaire contained questions related to treatment that covered 6 domains (ease and convenience, efficacy, burden, specialist, centre and general satisfaction). Adults completing the questionnaire could achieve a score from 0 to 100, with lower scores reflecting greater treatment satisfaction. The scale range for each of the 6 domains was 0-100 with lower scores reflecting greater treatment satisfaction. The scores of the domains at visit 3 (10th-15th ED), visit 5 (50th-55th ED) and end of trial (EoT) are presented.	Visit 3 (10th-15th ED); Visit 5 (50th-55th ED); End of trial (within 8 weeks of their last scheduled visit in the extension phase)
Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient)	Resource utilisation and caregiver burden are analysed in terms of average number of days absent from work and use of mobility aids (e.g. wheelchair or crutches) as a consequence of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial
Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient)	Resource utilisation and caregiver burden are analysed in terms of average number of days of absence from work and use of mobility aids (e.g. wheelchair or crutches) as a consequence of bleeds. The analysis was performed for the main phase (from Visit 2 to Visit 5 [50-55 exposure day], extension phase (from Visit 6 to end of trial; exposure day 100, expected to occur between 6 and 48 months of trial participation), the combined main and extension phase (from Visit 2 to end of trial) and for the inhibitor cohort.	From Visit 2 to Visit 5 (50-55 exposure day); From Visit 6 to end of trial, extension phase of the trial; From Visit 2 to end of trial, the combined main and extension phases of the trial

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2012
• Primary Completion (Actual): August 16, 2017
• Study Completion (Actual): December 5, 2018

Study Registration Dates

• First Submitted: December 15, 2011
• First Submitted That Met QC Criteria: December 15, 2011
• First Posted (Estimate): December 16, 2011

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

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
• Other Study ID Numbers: NN7008-3809; U1111-1119-6116 (Other Identifier: WHO); 2011-001033-16 (EudraCT Number); P/50/2010 (Other Identifier: EMA (PDCO)); JapicCTI-142544 (Other Identifier: JAPIC); CTR20150455 (Registry Identifier: ChinaDrugTrials)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No