guardian™4: Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Previously Untreated Children With Haemophilia A
Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT01493778
Collaborator
(none)
60
69
1
74.6
0.9
0
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
60 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Safety and Efficacy of Turoctocog Alfa in Prevention and Treatment of Bleeds in Paediatric Previously Untreated Patients With Haemophilia A
Actual Study Start Date
:
Sep 17, 2012
Actual Primary Completion Date
:
Aug 16, 2017
Actual Study Completion Date
:
Dec 5, 2018
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Incidence Rate of Factor VIII Inhibitors (Above or Equal to 0.6 BU (Bethesda Units)/mL) for the Main Phase of the Trial [From Visit 2 (21 days after screening) to Visit 5 (50-55 exposure day)]
The incidence rate (percentage of participants with inhibitors) of inhibitors defined as inhibitor titres ≥0.6 BU for main phase of the trial.
Secondary Outcome Measures
- Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None [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]
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.
- Annualised Bleeding Rate (ABR) [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 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.
- Number of Turoctocog Alfa (N8) Injections Required Per Bleed [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]
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.
- Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month [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]
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.
- Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year [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]
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.
- Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed [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]
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.
- Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention [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]
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.
- Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period [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 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.
- Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) [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]
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).
- Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL) [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 (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).
- Change in Total Scores for Parent Reported Treatment Satisfaction [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)]
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.
- Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) [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]
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.
- Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) [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]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
0 Years
to 6 Years
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Phoenix | Arizona | United States | 85016-7710 |
| 2 | Novo Nordisk Investigational Site | Long Beach | California | United States | 90806 |
| 3 | Novo Nordisk Investigational Site | Sacramento | California | United States | 95817 |
| 4 | Novo Nordisk Investigational Site | Washington | District of Columbia | United States | 20010-2978 |
| 5 | Novo Nordisk Investigational Site | Gainesville | Florida | United States | 32610 |
| 6 | Novo Nordisk Investigational Site | Orlando | Florida | United States | 32827 |
| 7 | Novo Nordisk Investigational Site | Tampa | Florida | United States | 33606 |
| 8 | Novo Nordisk Investigational Site | Tampa | Florida | United States | 33607 |
| 9 | Novo Nordisk Investigational Site | Augusta | Georgia | United States | 30912 |
| 10 | Novo Nordisk Investigational Site | Macon | Georgia | United States | 31201 |
| 11 | Novo Nordisk Investigational Site | Savannah | Georgia | United States | 31404 |
| 12 | Novo Nordisk Investigational Site | Oak Lawn | Illinois | United States | 60453 |
| 13 | Novo Nordisk Investigational Site | Detroit | Michigan | United States | 48201 |
| 14 | Novo Nordisk Investigational Site | Las Vegas | Nevada | United States | 89109 |
| 15 | Novo Nordisk Investigational Site | New Brunswick | New Jersey | United States | 08901 |
| 16 | Novo Nordisk Investigational Site | Brooklyn | New York | United States | 11201-5425 |
| 17 | Novo Nordisk Investigational Site | Brooklyn | New York | United States | 11220 |
| 18 | Novo Nordisk Investigational Site | Charlotte | North Carolina | United States | 28204 |
| 19 | Novo Nordisk Investigational Site | Cincinnati | Ohio | United States | 45229 |
| 20 | Novo Nordisk Investigational Site | Dayton | Ohio | United States | 45404 |
| 21 | Novo Nordisk Investigational Site | Oklahoma City | Oklahoma | United States | 73104 |
| 22 | Novo Nordisk Investigational Site | Portland | Oregon | United States | 97239 |
| 23 | Novo Nordisk Investigational Site | Charleston | South Carolina | United States | 29425 |
| 24 | Novo Nordisk Investigational Site | Salt Lake City | Utah | United States | 84113 |
| 25 | Novo Nordisk Investigational Site | Charlottesville | Virginia | United States | 22908 |
| 26 | Novo Nordisk Investigational Site | Algiers | Algeria | 16000 | |
| 27 | Novo Nordisk Investigational Site | Annaba | Algeria | 23000 | |
| 28 | Novo Nordisk Investigational Site | Graz | Austria | 8036 | |
| 29 | Novo Nordisk Investigational Site | Innsbruck | Austria | 6020 | |
| 30 | Novo Nordisk Investigational Site | Klagenfurt | Austria | A 9026 | |
| 31 | Novo Nordisk Investigational Site | Linz | Austria | 4020 | |
| 32 | Novo Nordisk Investigational Site | Salzburg | Austria | A 5020 | |
| 33 | Novo Nordisk Investigational Site | St. Poelten | Austria | A 3100 | |
| 34 | Novo Nordisk Investigational Site | Wien | Austria | A 1090 | |
| 35 | Novo Nordisk Investigational Site | Curitiba | Parana | Brazil | 80250-060 |
| 36 | Novo Nordisk Investigational Site | Campinas | Sao Paulo | Brazil | 13081-970 |
| 37 | Novo Nordisk Investigational Site | Beijing | Beijing | China | 100045 |
| 38 | Novo Nordisk Investigational Site | Chonqqing | Chongqing | China | 400014 |
| 39 | Novo Nordisk Investigational Site | Guangzhou | Guangdong | China | 510515 |
| 40 | Novo Nordisk Investigational Site | Tianjing | Tianjin | China | 300020 |
| 41 | Novo Nordisk Investigational Site | Hangzhou | Zhejiang | China | 310003 |
| 42 | Novo Nordisk Investigational Site | Beijing | China | 100032 | |
| 43 | Novo Nordisk Investigational Site | København Ø | Denmark | 2100 | |
| 44 | Novo Nordisk Investigational Site | Athens | Greece | GR-11527 | |
| 45 | Novo Nordisk Investigational Site | Thessaloniki | Greece | GR 54642 | |
| 46 | Novo Nordisk Investigational Site | Shatin, New Territories | Hong Kong | ||
| 47 | Novo Nordisk Investigational Site | Budapest | Hungary | 1089 | |
| 48 | Novo Nordisk Investigational Site | Debrecen | Hungary | 4032 | |
| 49 | Novo Nordisk Investigational Site | Aichi | Japan | 466-8560 | |
| 50 | Novo Nordisk Investigational Site | Hyogo | Japan | 654-0047 | |
| 51 | Novo Nordisk Investigational Site | Shizuoka | Japan | 420-8660 | |
| 52 | Novo Nordisk Investigational Site | Tokyo | Japan | 157-8535 | |
| 53 | Novo Nordisk Investigational Site | Vilnius | Lithuania | 08406 | |
| 54 | Novo Nordisk Investigational Site | Bydgoszcz | Poland | 85-094 | |
| 55 | Novo Nordisk Investigational Site | Lublin | Poland | 20-093 | |
| 56 | Novo Nordisk Investigational Site | Porto | Portugal | 4200-319 | |
| 57 | Novo Nordisk Investigational Site | San Juan | Puerto Rico | 00935 | |
| 58 | Novo Nordisk Investigational Site | Krasnodar | Russian Federation | 350007 | |
| 59 | Novo Nordisk Investigational Site | Moscow | Russian Federation | 119049 | |
| 60 | Novo Nordisk Investigational Site | Saint-Petersburg | Russian Federation | 191065 | |
| 61 | Novo Nordisk Investigational Site | Belgrade | Serbia | 11070 | |
| 62 | Novo Nordisk Investigational Site | Barcelona | Spain | 08035 | |
| 63 | Novo Nordisk Investigational Site | El Palmar | Spain | 30120 | |
| 64 | Novo Nordisk Investigational Site | Madrid | Spain | 28046 | |
| 65 | Novo Nordisk Investigational Site | Adana | Turkey | 01130 | |
| 66 | Novo Nordisk Investigational Site | Antalya | Turkey | 01010 | |
| 67 | Novo Nordisk Investigational Site | Bornova-IZMIR | Turkey | 35100 | |
| 68 | Novo Nordisk Investigational Site | Izmit | Turkey | 41380 | |
| 69 | Novo Nordisk Investigational Site | Samsun | Turkey | 55319 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01493778
Other Study ID Numbers:
- NN7008-3809
- U1111-1119-6116
- 2011-001033-16
- P/50/2010
- JapicCTI-142544
- CTR20150455
First Posted:
Dec 16, 2011
Last Update Posted:
Nov 30, 2020
Last Verified:
Nov 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at 40 sites in 15 countries: Algeria (1 site), Austria (2 sites), China (6 sites), Denmark (1 site), Greece (2 sites), Hong Kong (1 site), Hungary (1 site), Japan (2 sites), Lithuania (1 site), Poland (2 sites), Russian Federation (2 sites), Serbia (1 site), Spain (3 sites), Turkey (3 sites), United States (12). |
|---|---|
| Pre-assignment Detail | Sixty (60) participants were enrolled in the trial and received at least one dose of turoctocog alfa.The trial consisted of two phases: the main phase including the screening visit (visit 1) and 4 subsequent visits, and an extension phase with a rolling visit schedule consisting of 6 planned visits including 4 dispensing visits) per year. |
| Arm/Group Title | Turoctocog Alfa (N8) (Preventive+On-demand Treatment) |
|---|---|
| Arm/Group Description | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Participants who enrolled into the trial initiated the preventive treatment no later than their second birthday or after a maximum of 2 bleeding episodes requiring treatment, whichever came first. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. |
| Period Title: Overall Study | |
| STARTED | 60 |
| COMPLETED | 52 |
| NOT COMPLETED | 8 |
Baseline Characteristics
| Arm/Group Title | Turoctocog Alfa (N8) (Preventive+On-demand) |
|---|---|
| Arm/Group Description | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Participants who enrolled into the trial initiated the preventive treatment no later than their second birthday or after a maximum of 2 bleeding episodes requiring treatment, whichever came first. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. |
| Overall Participants | 60 |
| Age (Months) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Months] |
10.2
(7.88)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
0
0%
|
| Male |
60
100%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
5
8.3%
|
| Not Hispanic or Latino |
55
91.7%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
12
20%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
44
73.3%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
4
6.7%
|
Outcome Measures
| Title | Incidence Rate of Factor VIII Inhibitors (Above or Equal to 0.6 BU (Bethesda Units)/mL) for the Main Phase of the Trial |
|---|---|
| Description | The incidence rate (percentage of participants with inhibitors) of inhibitors defined as inhibitor titres ≥0.6 BU for main phase of the trial. |
| Time Frame | From Visit 2 (21 days after screening) to Visit 5 (50-55 exposure day) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was based on participants who completed the main phase of the trial. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) |
|---|---|
| Arm/Group Description | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. |
| Measure Participants | 58 |
| Number (95% Confidence Interval) [Percentage of participants] |
43.1
71.8%
|
| Title | Haemostatic Effect of Turoctocog Alfa on Treatment of Bleeds Assessed on a Predefined Four Point Scale: Excellent, Good, Moderate and None |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all dosed participants with data after dosing. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 51 | 58 | 49 | 59 | 26 |
| Measure bleeds | 98 | 133 | 269 | 402 | 179 |
| Excellent |
53
|
83
|
161
|
244
|
9
|
| Good |
36
|
29
|
73
|
102
|
19
|
| Moderate |
5
|
12
|
31
|
43
|
10
|
| None |
0
|
1
|
1
|
2
|
4
|
| Missing |
4
|
8
|
3
|
11
|
137
|
| Title | Annualised Bleeding Rate (ABR) |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis (FAS) set included all dosed participants with data after dosing. Participants in FAS with only one exposure day were excluded from preventive treatment in main when calculating the Poisson estimates of ABR as the small amount of information introduces uncertainty to the estimated ABR. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 51 | 58 | 49 | 59 | 26 |
| Measure bleeding episodes | 98 | 133 | 269 | 402 | 179 |
| Mean (95% Confidence Interval) [bleeds/patient/year] |
4.27
|
5.63
|
3.81
|
4.26
|
6.09
|
| Title | Number of Turoctocog Alfa (N8) Injections Required Per Bleed |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set included all dosed participants with data after dosing. Number of participants analysed=number of participants with bleeding episodes. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 36 | 38 | 40 | 52 | 26 |
| Measure bleeds | 98 | 133 | 269 | 402 | 179 |
| Mean (Standard Deviation) [injections/bleed] |
2.1
(2.18)
|
1.8
(2.98)
|
2.4
(3.04)
|
2.2
(3.03)
|
2.8
(6.24)
|
| Title | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Month |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set included all dosed participants with data after dosing. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 51 | 58 | 49 | 59 | 26 |
| Mean (Standard Deviation) [IU/kg/month/patient] |
117.6
(190.7)
|
359.8
(323.2)
|
476.9
(209.3)
|
437.2
(244.4)
|
1815.2
(1653.8)
|
| Title | Total Consumption of Turoctocog Alfa (N8) Per Patient (Prevention, Treatment of Bleeds and During Surgery) Per Year |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set included all dosed participants with data after dosing. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 51 | 58 | 49 | 59 | 26 |
| Mean (Standard Deviation) [IU/kg/year/patient] |
1410.8
(2288.4)
|
4317.2
(3878.9)
|
5722.5
(2512.0)
|
5245.9
(2933.1)
|
21782.8
(19845.6)
|
| Title | Consumption of Turoctocog Alfa (N8) (IU/kg/Bleed) Per Bleed |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all dosed participants with data after dosing. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 51 | 58 | 49 | 59 | 26 |
| Measure bleeds | 98 | 133 | 269 | 402 | 179 |
| Mean (Standard Deviation) [IU/kg/bleed] |
86.1
(116.8)
|
80.8
(126.4)
|
107.9
(137.7)
|
98.9
(134.5)
|
279.1
(821.7)
|
| Title | Consumption of Turoctocog Alfa (N8) (IU/kg/Months) for Bleed Prevention |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all dosed participants with data after dosing. Participants in on-demand treatment did not receive treatment for bleed prevention and therefore are not included in the analysis. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 0 | 58 | 49 | 59 | 26 |
| Mean (Standard Deviation) [IU/kg/month/patient] |
293.5
(281.1)
|
446.3
(206.2)
|
399.0
(234.7)
|
1692.6
(1553.9)
|
| Title | Frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) Reported During the Trial Period |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set included all dosed participants with data after dosing. The arm group - 'main phase' includes subjects who were treated both on-demand and preventively in the main phase. 'On-Demand' and 'Preventive' were not described as separate arms/groups in the protocol. These were not analysed separately for this endpoint. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|
| Arm/Group Description | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 60 | 49 | 60 | 26 |
| All adverse events |
5.85
|
3.76
|
5.12
|
7.41
|
| Serious adverse events |
1.02
|
0.24
|
0.73
|
1.52
|
| Title | Incidence Rate of Clinically Relevant Inhibitors Defined as an Inhibitor Titre (≥ 0.6 BU/mL) Combined With a Decreased Recovery (<66% of Expected Level) |
|---|---|
| Description | 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). |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all dosed participants with data after dosing. The arm group - 'main phase' includes subjects who were treated both on-demand and preventively in the main phase. 'On-Demand' and 'Preventive' were not described as separate arms/groups in the protocol. These were not analysed separately for this endpoint. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment |
|---|---|---|---|
| Arm/Group Description | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. |
| Measure Participants | 58 | 33 | 58 |
| One-stage FVIII clotting activity assay |
36.2
60.3%
|
3.0
NaN
|
37.9
NaN
|
| Two-stage chromogenic assay |
36.2
60.3%
|
3.0
NaN
|
37.9
NaN
|
| Title | Incidence Rate of High-titre Inhibitors Defined as Inhibitor Titre ≥ 5 BU (Bethesda Units)/mL) |
|---|---|
| Description | 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). |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all dosed participants with data after dosing. The arm group - 'main phase' includes subjects who were treated both on-demand and preventively in the main phase. 'On-Demand' and 'Preventive' were not described as separate arms/groups in the protocol. These were not analysed separately for this endpoint. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment |
|---|---|---|---|
| Arm/Group Description | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. |
| Measure Participants | 58 | 33 | 58 |
| Number (95% Confidence Interval) [Percentage of participants] |
27.6
46%
|
0.0
NaN
|
27.6
NaN
|
| Title | Change in Total Scores for Parent Reported Treatment Satisfaction |
|---|---|
| Description | 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. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all dosed participants with data after dosing. Number of participants analysed=number of participants who answered the questionnaire |
| Arm/Group Title | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment |
|---|---|
| Arm/Group Description | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. |
| Measure Participants | 59 |
| Ease/convenience visit 3 Range: 0 - 100 |
27.1
(14.6)
|
| Ease and convenience - visit 5 Score range: 0-100 |
21.4
(14.9)
|
| Ease and convenience - EoT Score range:0-100 |
21.9
(13.4)
|
| Efficacy - visit 3 Score range: 0-100 |
10.2
(12.8)
|
| Efficacy - visit 5 Score range: 0-100 |
9.8
(10.5)
|
| Efficacy - end of trial Score range: 0-100 |
11.7
(17.4)
|
| Burden - visit 3 Score range: 0-100 |
20.5
(21.0)
|
| Burden - visit 5 Score range: 0-100 |
15.4
(17.4)
|
| Burden - end of trial Score range: 0-100 |
16.9
(16.6)
|
| Specialist/Nurses- visit 3 Score range: 0-100 |
4.1
(8.4)
|
| Specialist/Nurses- visit 5 Score range: 0-100 |
4.0
(6.6)
|
| Specialist/Nurses- end of trial Score range: 0-100 |
4.9
(8.2)
|
| Centre/Hospital - visit 3 Score range: 0-100 |
2.8
(5.7)
|
| Centre/Hospital - visit 5 Score range: 0-100 |
3.1
(5.7)
|
| Centre/Hospital - end of trial Score range: 0-100 |
5.0
(8.9)
|
| General satisfaction - visit 3 Score range: 0-100 |
5.7
(10.7)
|
| General satisfaction - visit 5 Score range: 0-100 |
3.8
(8.5)
|
| General satisfaction - end of trial Range: 0-100 |
6.4
(15.3)
|
| Title | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Month Per Patient) |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all dosed participants with data after dosing. Number of participants analysed=number of participants with data available |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 51 | 58 | 49 | 59 | 26 |
| Caregiver/parent's absence from work |
0.011
(0.050)
|
0.533
(1.645)
|
0.007
(0.027)
|
0.232
(1.117)
|
0.271
(0.641)
|
| Patient's use of mobility aids |
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
0.025
(0.084)
|
| Title | Health Resource Utilization and Caregiver Burden Associated With Bleeds (Per Year Per Patient) |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set included all dosed participants with data after dosing. Number of participants analysed=number of participants with data available. |
| Arm/Group Title | Turoctocog Alfa (N8): Main Phase (On-demand Treatment) | Turoctocog Alfa (N8): Main Phase (Preventive Treatment) | Turoctocog Alfa (N8): Extension Phase (Preventive Treatment) | Turoctocog Alfa (N8): Combined-Main+Ext, Preventive Treatment | Turoctocog Alfa (N8): Inhibitor Cohort |
|---|---|---|---|---|---|
| Arm/Group Description | Participants (children≤2 years) received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection as on-demand treatment while waiting to start on a preventive regimen. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. This treatment period included Visit 2 to first preventive dose. | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Subjects received prophylactic factor VIII replacement therapy (preventive treatment) until Visit 5 or until development of inhibitor, whichever came first. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. | Participants received prophylactic treatment administered from completion of the main phase or completion of the inhibitor cohort until the end-of-trial visit in the extension phase. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. After completing the main phase, participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). | Participants who started preventive treatment in the main and extension phase are included in this arm. They received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the child's clinical profile. The trial consisted of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reached a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which translated into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | Participants who developed an inhibitor during the course of the trial and followed an alternative treatment regimen are included in this arm. They were offered continued treatment with turoctocog alfa for up to 24 months. |
| Measure Participants | 51 | 58 | 49 | 59 | 26 |
| Caregiver/parent's absence from work |
0.127
(0.601)
|
6.396
(19.736)
|
0.082
(0.319)
|
2.779
(13.406)
|
3.252
(7.691)
|
| Patient's use of mobility aids |
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
0.296
(1.006)
|
Adverse Events
| Time Frame | Adverse events from the first trial related activity after the participant had signed the informed consent (visit 1) until the end-of-trial visit (within 8 weeks of their last scheduled visit in the extension phase; 100th exposure day). | |
|---|---|---|
| Adverse Event Reporting Description | Reported adverse events were based on the safety analysis set including all dosed participants with data after dosing. | |
| Arm/Group Title | Turoctocog Alfa | |
| Arm/Group Description | Participants received turoctocog alfa doses of 15-60 IU/kg body weight (BW) administered as an intravenous injection for the prevention of bleeding. The investigator decided what dose of turoctocog alfa to give based on the participant's clinical profile. Participants who enrolled into the trial initiated the preventive treatment no later than their second birthday or after a maximum of 2 bleeding episodes requiring treatment, whichever came first. The trial consists of two phases. In the main phase, an aggregated number of at least 50 participants received preventive treatment with turoctocog alfa until they reach a minimum of 50 exposure days (ED) or until they developed inhibitors. After that the participants continued in the extension phase where at least 50 participants achieved at least 100 ED, which will translate into a maximum trial duration of up to 5 years (including any potential inhibitor treatment). The estimated total duration of the trial was approximately 7 years. | |
All Cause Mortality |
||
| Turoctocog Alfa | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/60 (0%) | |
Serious Adverse Events |
||
| Turoctocog Alfa | ||
| Affected / at Risk (%) | # Events | |
| Total | 36/60 (60%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 3/60 (5%) | 3 |
| Factor VIII inhibition | 25/60 (41.7%) | 27 |
| Congenital, familial and genetic disorders | ||
| Cryptorchism | 1/60 (1.7%) | 1 |
| Hydrocele | 1/60 (1.7%) | 1 |
| Gastrointestinal disorders | ||
| Gastritis | 1/60 (1.7%) | 1 |
| Mouth haemorrhage | 1/60 (1.7%) | 2 |
| General disorders | ||
| Catheter site haematoma | 2/60 (3.3%) | 2 |
| Catheter site oedema | 1/60 (1.7%) | 1 |
| Pyrexia | 4/60 (6.7%) | 4 |
| Immune system disorders | ||
| Drug hypersensitivity | 2/60 (3.3%) | 2 |
| Infections and infestations | ||
| Bacteraemia | 1/60 (1.7%) | 1 |
| Bronchitis | 1/60 (1.7%) | 1 |
| Catheter site infection | 2/60 (3.3%) | 6 |
| Device related infection | 3/60 (5%) | 5 |
| Gastroenteritis | 2/60 (3.3%) | 3 |
| Gastrointestinal infection | 1/60 (1.7%) | 1 |
| Injection site infection | 1/60 (1.7%) | 1 |
| Nasopharyngitis | 1/60 (1.7%) | 1 |
| Otitis media acute | 1/60 (1.7%) | 1 |
| Respiratory tract infection | 1/60 (1.7%) | 1 |
| Staphylococcal bacteraemia | 2/60 (3.3%) | 3 |
| Staphylococcal infection | 1/60 (1.7%) | 1 |
| Streptococcal bacteraemia | 1/60 (1.7%) | 1 |
| Systemic bacterial infection | 1/60 (1.7%) | 1 |
| Upper respiratory tract infection | 2/60 (3.3%) | 2 |
| Vascular device infection | 2/60 (3.3%) | 2 |
| Viral infection | 1/60 (1.7%) | 1 |
| Injury, poisoning and procedural complications | ||
| Accidental overdose | 1/60 (1.7%) | 1 |
| Concussion | 1/60 (1.7%) | 1 |
| Head injury | 3/60 (5%) | 3 |
| Traumatic haemorrhage | 4/60 (6.7%) | 5 |
| Musculoskeletal and connective tissue disorders | ||
| Joint effusion | 1/60 (1.7%) | 1 |
| Nervous system disorders | ||
| Haemorrhage intracranial | 1/60 (1.7%) | 1 |
| Intracranial haematoma | 1/60 (1.7%) | 1 |
| Product Issues | ||
| Device damage | 1/60 (1.7%) | 1 |
| Device dislocation | 1/60 (1.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Acute respiratory failure | 1/60 (1.7%) | 1 |
| Status asthmaticus | 1/60 (1.7%) | 1 |
| Surgical and medical procedures | ||
| Central venous catheter removal | 1/60 (1.7%) | 2 |
| Central venous catheterisation | 2/60 (3.3%) | 2 |
| Circumcision | 2/60 (3.3%) | 2 |
| Hospitalisation | 1/60 (1.7%) | 1 |
| Vascular disorders | ||
| Haematoma | 1/60 (1.7%) | 1 |
| Phlebitis deep | 1/60 (1.7%) | 1 |
| Poor venous access | 1/60 (1.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Turoctocog Alfa | ||
| Affected / at Risk (%) | # Events | |
| Total | 55/60 (91.7%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 6/60 (10%) | 8 |
| Factor VIII inhibition | 4/60 (6.7%) | 4 |
| Iron deficiency anaemia | 8/60 (13.3%) | 12 |
| Gastrointestinal disorders | ||
| Constipation | 3/60 (5%) | 3 |
| Diarrhoea | 12/60 (20%) | 25 |
| Teething | 3/60 (5%) | 3 |
| Vomiting | 11/60 (18.3%) | 19 |
| General disorders | ||
| Catheter site inflammation | 3/60 (5%) | 3 |
| Pyrexia | 32/60 (53.3%) | 85 |
| Infections and infestations | ||
| Bronchitis | 7/60 (11.7%) | 7 |
| Catheter site infection | 3/60 (5%) | 7 |
| Conjunctivitis | 3/60 (5%) | 3 |
| Ear infection | 6/60 (10%) | 10 |
| Gastroenteritis | 8/60 (13.3%) | 8 |
| Gastroenteritis viral | 3/60 (5%) | 4 |
| Hand-foot-and-mouth disease | 4/60 (6.7%) | 5 |
| Influenza | 5/60 (8.3%) | 5 |
| Nasopharyngitis | 16/60 (26.7%) | 36 |
| Otitis media | 4/60 (6.7%) | 4 |
| Otitis media acute | 4/60 (6.7%) | 7 |
| Pharyngitis | 4/60 (6.7%) | 4 |
| Pneumonia | 5/60 (8.3%) | 5 |
| Tonsillitis | 3/60 (5%) | 6 |
| Upper respiratory tract infection | 15/60 (25%) | 64 |
| Varicella | 3/60 (5%) | 3 |
| Viral infection | 7/60 (11.7%) | 9 |
| Viral upper respiratory tract infection | 4/60 (6.7%) | 11 |
| Injury, poisoning and procedural complications | ||
| Arthropod bite | 4/60 (6.7%) | 5 |
| Contusion | 6/60 (10%) | 9 |
| Head injury | 5/60 (8.3%) | 9 |
| Investigations | ||
| Body temperature increased | 3/60 (5%) | 4 |
| Metabolism and nutrition disorders | ||
| Iron deficiency | 4/60 (6.7%) | 4 |
| Reproductive system and breast disorders | ||
| Balanoposthitis | 3/60 (5%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 15/60 (25%) | 26 |
| Nasal congestion | 4/60 (6.7%) | 6 |
| Rhinorrhoea | 7/60 (11.7%) | 10 |
| Skin and subcutaneous tissue disorders | ||
| Dermatitis diaper | 3/60 (5%) | 3 |
| Eczema | 5/60 (8.3%) | 6 |
| Rash | 5/60 (8.3%) | 11 |
| Rash papular | 3/60 (5%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Results Point of Contact
| Name/Title | Clinical Reporting Anchor and Disclosure (1452) |
|---|---|
| Organization | Novo Nordisk A/S |
| Phone | (+1) 866-867-7178 |
| clinicaltrials@novonordisk.com |
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT01493778
Other Study ID Numbers:
- NN7008-3809
- U1111-1119-6116
- 2011-001033-16
- P/50/2010
- JapicCTI-142544
- CTR20150455
First Posted:
Dec 16, 2011
Last Update Posted:
Nov 30, 2020
Last Verified:
Nov 1, 2020