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

Congenital Bleeding Disorder Clinical Trial

— guardian™4  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01493778
• Other study ID #: NN7008-3809
• Secondary ID: U1111-1119-61162
• Status: Completed
• Phase: Phase 3
• Start date: September 17, 2012
• Est. completion date: December 5, 2018

Study information

• Verified date: November 2020
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 5, 2018
• Est. primary completion date: August 16, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 6 Years

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

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.

Locations

Country	Name	City	State
Algeria	Novo Nordisk Investigational Site	Algiers
Algeria	Novo Nordisk Investigational Site	Annaba
Austria	Novo Nordisk Investigational Site	Graz
Austria	Novo Nordisk Investigational Site	Innsbruck
Austria	Novo Nordisk Investigational Site	Klagenfurt
Austria	Novo Nordisk Investigational Site	Linz
Austria	Novo Nordisk Investigational Site	Salzburg
Austria	Novo Nordisk Investigational Site	St. Poelten
Austria	Novo Nordisk Investigational Site	Wien
Brazil	Novo Nordisk Investigational Site	Campinas	Sao Paulo
Brazil	Novo Nordisk Investigational Site	Curitiba	Parana
China	Novo Nordisk Investigational Site	Beijing	Beijing
China	Novo Nordisk Investigational Site	Beijing
China	Novo Nordisk Investigational Site	Chonqqing	Chongqing
China	Novo Nordisk Investigational Site	Guangzhou	Guangdong
China	Novo Nordisk Investigational Site	Hangzhou	Zhejiang
China	Novo Nordisk Investigational Site	Tianjing	Tianjin
Denmark	Novo Nordisk Investigational Site	København Ø
Greece	Novo Nordisk Investigational Site	Athens
Greece	Novo Nordisk Investigational Site	Thessaloniki
Hong Kong	Novo Nordisk Investigational Site	Shatin, New Territories
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Debrecen
Japan	Novo Nordisk Investigational Site	Aichi
Japan	Novo Nordisk Investigational Site	Hyogo
Japan	Novo Nordisk Investigational Site	Shizuoka
Japan	Novo Nordisk Investigational Site	Tokyo
Lithuania	Novo Nordisk Investigational Site	Vilnius
Poland	Novo Nordisk Investigational Site	Bydgoszcz
Poland	Novo Nordisk Investigational Site	Lublin
Portugal	Novo Nordisk Investigational Site	Porto
Puerto Rico	Novo Nordisk Investigational Site	San Juan
Russian Federation	Novo Nordisk Investigational Site	Krasnodar
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Serbia	Novo Nordisk Investigational Site	Belgrade
Spain	Novo Nordisk Investigational Site	Barcelona
Spain	Novo Nordisk Investigational Site	El Palmar
Spain	Novo Nordisk Investigational Site	Madrid
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
United States	Novo Nordisk Investigational Site	Augusta	Georgia
United States	Novo Nordisk Investigational Site	Brooklyn	New York
United States	Novo Nordisk Investigational Site	Brooklyn	New York
United States	Novo Nordisk Investigational Site	Charleston	South Carolina
United States	Novo Nordisk Investigational Site	Charlotte	North Carolina
United States	Novo Nordisk Investigational Site	Charlottesville	Virginia
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	Gainesville	Florida
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Long Beach	California
United States	Novo Nordisk Investigational Site	Macon	Georgia
United States	Novo Nordisk Investigational Site	New Brunswick	New Jersey
United States	Novo Nordisk Investigational Site	Oak Lawn	Illinois
United States	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma
United States	Novo Nordisk Investigational Site	Orlando	Florida
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Portland	Oregon
United States	Novo Nordisk Investigational Site	Sacramento	California
United States	Novo Nordisk Investigational Site	Salt Lake City	Utah
United States	Novo Nordisk Investigational Site	Savannah	Georgia
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Algeria,  Austria,  Brazil,  China,  Denmark,  Greece,  Hong Kong,  Hungary,  Japan,  Lithuania,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Serbia,  Spain,  Turkey, 

Outcome

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

External Links

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