Clinical Trial Results:
A Multi-Centre, Open-Label, Non-Controlled Trial on Safety and Efficacy of N8 in Previously Treated Paediatric Patients with Haemophilia A
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Summary
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EudraCT number |
2009-016383-36 |
Trial protocol |
IT LT |
Global end of trial date |
21 Nov 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Mar 2016
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First version publication date |
26 Jul 2015
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
NN7008-3545
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01138501 | ||
WHO universal trial number (UTN) |
U1111-1113-7182 | ||
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Sponsors
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Sponsor organisation name |
Novo Nordisk A/S
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Sponsor organisation address |
Novo Allé, Bagsvaerd, Denmark, 2880
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Public contact |
Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Global Clinical Registry (GCR, 1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000428-PIP01-08 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Mar 2012
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Nov 2011
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Nov 2011
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate safety of N8 (turoctocog alfa) in paediatric previously treated patients (PTPs) <12 years of age with haemophilia A
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki (2008) and ICH Good Clinical Practice (1996). The results presented reflect data available in the clinical database as of 13 -Dec-2011. The database was updated on 1-Feb-2012 in order to change the coding of one adverse event coded as ‘anti-factor VIII antibody positive’. The results of a second separately drawn sample from this patient was negative, meaning that the definition of FVIII inhibitors was not met and the coding of the event was therefore changed to ‘anti-factor VIII antibody test’.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
18 Jun 2010
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
53 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Brazil: 9
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Lithuania: 4
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Country: Number of subjects enrolled |
Macedonia, the former Yugoslav Republic of: 5
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Country: Number of subjects enrolled |
Malaysia: 5
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Country: Number of subjects enrolled |
Poland: 5
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Country: Number of subjects enrolled |
Russian Federation: 8
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Country: Number of subjects enrolled |
Serbia: 5
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Country: Number of subjects enrolled |
Taiwan: 1
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Country: Number of subjects enrolled |
Turkey: 7
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Country: Number of subjects enrolled |
United States: 12
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Worldwide total number of subjects |
63
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EEA total number of subjects |
11
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
4
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Children (2-11 years) |
59
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 26 sites enrolled and dosed at least one patient. The country distribution was as follows (number of actively recruiting sites per country in parenthesis): Brazil (3), Italy (1), Lithuania (1), Macedonia (1), Malaysia (1), Poland (2), Russia (2), Serbia (1), Taiwan (1), Turkey (3) and the US (10) | ||||||||||||||
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Pre-assignment
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Screening details |
Not Applicable | ||||||||||||||
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Period 1
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Period 1 title |
Overall (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
Not applicable
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Arms
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Arm title
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All subjects treated with Turoctocog Alfa | ||||||||||||||
Arm description |
The patients received bleeding preventive treatment with a single dose of turoctocog alfa of 25-50 IU/kg every second day or 25-60 IU/kg three times weekly. Turoctocog alfa was administered as a slow bolus i.v. injection (approximately 1-2 mL/min). Pharmacokinetic assessments were performed in at least 13 patients from each age cohort. Each patient participating in the pharmacokinetic assessments received one dose of previous factor VIII (FVIII) and one dose of turoctocog alfa. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
N8
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Investigational medicinal product code |
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Other name |
Turoctocog Alfa
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous bolus use
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Dosage and administration details |
A single dose of turoctocog alfa of 25-50 IU/kg every second day or 25-60 IU/kg three times weekly was administered as a slow bolus i.v. injection (approximately 1-2 mL/min). Each patient participating in the pharmacokinetic assessments received one dose of previous FVIII and one dose of turoctocog alfa.
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Baseline characteristics reporting groups
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Reporting group title |
All subjects treated with Turoctocog Alfa
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Reporting group description |
The patients received bleeding preventive treatment with a single dose of turoctocog alfa of 25-50 IU/kg every second day or 25-60 IU/kg three times weekly. Turoctocog alfa was administered as a slow bolus i.v. injection (approximately 1-2 mL/min). Pharmacokinetic assessments were performed in at least 13 patients from each age cohort. Each patient participating in the pharmacokinetic assessments received one dose of previous factor VIII (FVIII) and one dose of turoctocog alfa. | |||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All subjects treated with Turoctocog Alfa
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Reporting group description |
The patients received bleeding preventive treatment with a single dose of turoctocog alfa of 25-50 IU/kg every second day or 25-60 IU/kg three times weekly. Turoctocog alfa was administered as a slow bolus i.v. injection (approximately 1-2 mL/min). Pharmacokinetic assessments were performed in at least 13 patients from each age cohort. Each patient participating in the pharmacokinetic assessments received one dose of previous factor VIII (FVIII) and one dose of turoctocog alfa. | ||
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End point title |
The incidence rate of FVIII inhibitors (≥0.6 BU/mL) [1] | ||||||
End point description |
The incidence rate of FVIII inhibitors was calculated by having all patients with inhibitors in the nominator and including all patients with a minimum 50 exposure plus any patients with less than 50 exposures but with inhibitors in denominator.
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End point type |
Primary
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End point timeframe |
The adverse events were collected throughout the trial which corresponded to an average of 138 days per subject.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: A one-sided 97.5% upper confidence limit for the incidence rate of FVIII inhibitors was provided based on an exact calculation for a binomial distribution. Adequate safety with regard to inhibitors was concluded if the upper one-sided 97.5% confidence limit was below 10.7%. Result : The one-sided 97.5% upper confidence limit for the inhibitor incidence rate of zero was 6.06%. |
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
The adverse events were collected throughout the trial, corresponding to an average of 138 days per subject.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
14.1
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Reporting groups
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Reporting group title |
All subjects treated with Turoctocog Alfa
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Reporting group description |
The patients received bleeding preventive treatment with a single dose of turoctocog alfa of 25-50 IU/kg every second day or 25-60 IU/kg three times weekly. Turoctocog alfa was administered as a slow bolus i.v. injection (approximately 1-2 mL/min). Pharmacokinetic assessments were performed in at least 13 patients from each age cohort. Each patient participating in the pharmacokinetic assessments received one dose of previous factor VIII (FVIII) and one dose of turoctocog alfa. | ||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Not applicable | |||
