Clinical Trial Results:
Safety of turoctocog alfa for prophylaxis and treatment of bleeding episodes in previously treated patients with moderate or severe haemophilia A in India
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Summary
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EudraCT number |
2017-002281-46 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
22 Apr 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Oct 2019
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First version publication date |
25 Oct 2019
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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 |
NN7008-4304
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03449342 | ||
WHO universal trial number (UTN) |
U1111-1179-5950 | ||
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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 |
Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
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Scientific contact |
Clinical Reporting Anchor and Disclosure (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) |
No
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Aug 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 Mar 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Apr 2019
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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 assess safety of turoctocog alfa during treatment and prophylaxis of bleeding episodes in previously treated patients with moderate or severe haemophilia A in India
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Protection of trial subjects |
The trial was conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice, including archiving of essential documents.
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Background therapy |
Not applicable | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
23 Feb 2018
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Long term follow-up planned |
No
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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 |
India: 60
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Worldwide total number of subjects |
60
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EEA total number of subjects |
0
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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) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
10
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Adults (18-64 years) |
50
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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 |
The trial was conducted at 10 sites in India. | |||||||||
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Pre-assignment
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Screening details |
A washout period for a minimum of 72 hours for factor 8 (FVIII) containing products prior to collection of FVIII activity and FVIII inhibitor laboratory samples at visit 1 (screening) was done to ensure subject eligibility. Prior to visit 4 (end of trial), a washout of minimum 48 hours was done to avoid interference with the FVIII inhibitor assay | |||||||||
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Period 1
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Period 1 title |
Overall Study (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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Are arms mutually exclusive |
Yes
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Arm title
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Adolescents (12 - <18 years) | |||||||||
Arm description |
Participants were to receive preventive turoctocog alfa at a frequency of ‘every second day’ or ‘3 times a week’ at a dose in the range of 20-50 IU/kg at the investigator’s discretion. The total treatment duration for each participant was 8 weeks. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
TUROCTOCOG ALFA
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Investigational medicinal product code |
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Other name |
NovoEight®
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dosing for prophylaxis was according to the approved prescribing information. The recommended frequency of dosing could be either every second day or 3 times weekly, at a dose in the range of 20-50 IU/kg. Bleeds were treated with one or more turoctocog alfa intravenous (i.v.) bolus injections. The individual dose levels were decided by the investigator based on recommendations from the World Federation of Hemophilia (WFH). Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations and the following guidance: Minor surgery; to maintain FVIII activity levels at 30−60 IU/dL.
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Arm title
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Adults (≥18 years) | |||||||||
Arm description |
Participants were to receive preventive turoctocog alfa at a frequency of ‘every second day’ or ‘3 times a week’ at a dose in the range of 20-50 IU/kg at the investigator’s discretion. The total treatment duration for each participant was 8 weeks. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
TUROCTOCOG ALFA
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Investigational medicinal product code |
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Other name |
NovoEight®
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dosing for prophylaxis was according to the approved prescribing information. The recommended frequency of dosing could be either every second day or 3 times weekly, at a dose in the range of 20-50 IU/kg. Bleeds were treated with one or more turoctocog alfa i.v. bolus injections. The individual dose levels were decided by the investigator based on recommendations from the WFH. Participants who underwent surgery were treated with turoctocog alfa according to WFH recommendations and the following guidance: Minor surgery; to maintain FVIII activity levels at 30−60 IU/dL.
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Baseline characteristics reporting groups
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Reporting group title |
Adolescents (12 - <18 years)
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Reporting group description |
Participants were to receive preventive turoctocog alfa at a frequency of ‘every second day’ or ‘3 times a week’ at a dose in the range of 20-50 IU/kg at the investigator’s discretion. The total treatment duration for each participant was 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Adults (≥18 years)
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Reporting group description |
Participants were to receive preventive turoctocog alfa at a frequency of ‘every second day’ or ‘3 times a week’ at a dose in the range of 20-50 IU/kg at the investigator’s discretion. The total treatment duration for each participant was 8 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Adolescents (12 - <18 years)
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Reporting group description |
Participants were to receive preventive turoctocog alfa at a frequency of ‘every second day’ or ‘3 times a week’ at a dose in the range of 20-50 IU/kg at the investigator’s discretion. The total treatment duration for each participant was 8 weeks. | ||
Reporting group title |
Adults (≥18 years)
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Reporting group description |
Participants were to receive preventive turoctocog alfa at a frequency of ‘every second day’ or ‘3 times a week’ at a dose in the range of 20-50 IU/kg at the investigator’s discretion. The total treatment duration for each participant was 8 weeks. | ||
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End point title |
Occurrence of confirmed FVIII inhibitor development (≥ 0.6 BU) [1] | ||||||||||||
End point description |
The number of participants who confirmed the presence of FVIII inhibitor development (≥ 0.6 BU) during the trial. Results are based on the full analysis set (FAS), that included all dosed participants with data after dosing during 8 weeks of treatment.
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End point type |
Primary
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End point timeframe |
During 8 weeks of treatment
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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: The primary endpoint investigated safety and was analysed using descriptive statistics, and thus no statistical analysis was performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Frequency of adverse drug reactions (AR) and serious adverse reactions (SAR) | ||||||||||||||||||
End point description |
Frequency of adverse drug reactions (ARs) and serious adverse reactions (SARs) are presented as rate of events, which was calculated as the number of ARs per patient years. All presented ARs and SARs are treatment emergent and related to trial product, which were defined as the events reported after trial product administration until the follow-up, 12 weeks after first treatment. Results are based on the safety analysis set, that included all dosed participants with data after dosing during 8 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
Reported until follow-up, 12 weeks after first treatment
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Successful haemostatic effect of turoctocog alfa in the treatment of bleeding episodes | ||||||||||||
End point description |
The haemostatic effect of turoctocog alfa when used for treatment of bleeding episodes was evaluated during 8 weeks of treatment. Results are based on the FAS that included all dosed participants with data after dosing during 8 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
During 8 weeks of treatment
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| Notes [2] - Number of subjects analysed = number of bleeding episodes treated with turoctocog alfa [3] - Number of subjects analysed = number of bleeding episodes treated with turoctocog alfa |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Total annualised consumption of turoctocog alfa | ||||||||||||
End point description |
Total consumption of turoctocog alfa (IU/kg body weight (BW) per year) per participant was evaluated during 8 weeks of treatment. Results are based on the FAS that included all dosed participants with data after dosing during 8 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
Measured during the 8 weeks of treatment
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Frequency of allergic or infusion reactions related to the trial product | ||||||||||||
End point description |
Frequency of allergic or infusion reactions related to trial products are presented as rate of adverse reactions, which was calculated as the number of reactions per patient years. Allergic reactions are a class of adverse events related to allergy. Results are based on the safety analysis set, that included all dosed participants with data after dosing during 8 weeks of treatment.
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End point type |
Secondary
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End point timeframe |
Reported until follow-up, 12 weeks after first treatment
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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 |
Week 0 - 12 (8 weeks of treatment period + 4 weeks of follow-up period).
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Adverse event reporting additional description |
All the adverse events are based on the SAS which included all dosed participants with data after dosing. 'Number of deaths causally related to treatment’ is the data considered to present under 'total number of deaths resulting from adverse events’.
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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 |
21
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Reporting groups
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Reporting group title |
Adolescents (12 - <18 years)
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Reporting group description |
Participants were to receive preventive turoctocog alfa at a frequency of ‘every second day’ or ‘3 times a week’ at a dose in the range of 20-50 IU/kg at the investigator’s discretion. The total treatment duration for each participant was 8 weeks. | |||||||||||||||||||||||||||||||||
Reporting group title |
Adults (≥18 years)
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Reporting group description |
Participants were to receive preventive turoctocog alfa at a frequency of ‘every second day’ or ‘3 times a week’ at a dose in the range of 20-50 IU/kg at the investigator’s discretion. The total treatment duration for each participant was 8 weeks. | |||||||||||||||||||||||||||||||||
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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. | |||
| None reported | |||
