Stránka klinických studií Nct
Clinical Trial Results:
Safety in Haemolytic PNH Patients Treated with Eculizumab: A Multi-center Open-label Research Design Study (SHEPHERD)
| Summary | |
EudraCT number | 2004-002795-42 |
Trial protocol | SE IE DE GB IT ES |
Global end of trial date | 18 Oct 2006 |
| Results information | |
Results version number | v1(current) |
This version publication date | 06 Jan 2017 |
First version publication date | 06 Jan 2017 |
Other versions | |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
| |||
| Trial identification | |||
Sponsor protocol code | C04-002 | ||
| Additional study identifiers | |||
ISRCTN number | - | ||
US NCT number | NCT00122304 | ||
WHO universal trial number (UTN) | - | ||
| Sponsors | |||
Sponsor organisation name | Alexion Pharmaceuticals Incorporated | ||
Sponsor organisation address | 100 College Street, New Haven, CT, United States, 06510 | ||
Public contact | European Clinical Trial Information, Alexion Europe SAS, +33 1 47 10 06 06, clinicaltrials.eu@alexion.com | ||
Scientific contact | European Clinical Trial Information, Alexion Europe SAS, +33 1 47 10 06 06, clinicaltrials.eu@alexion.com | ||
| Paediatric regulatory details | |||
Is trial part of an agreed paediatric investigation plan (PIP) | No | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
| Results analysis stage | |||
Analysis stage | Final | ||
Date of interim/final analysis | 06 Jan 2007 | ||
Is this the analysis of the primary completion data? | Yes | ||
Primary completion date | 21 Mar 2006 | ||
Global end of trial reached? | Yes | ||
Global end of trial date | 18 Oct 2006 | ||
Was the trial ended prematurely? | No | ||
| General information about the trial | |||
Main objective of the trial | The primary objective was to evaluate the safety of eculizumab in patients with transfusion-dependent haemolytic paroxysmal nocturnal haemoglobinuria (PNH) | ||
Protection of trial subjects | Patients must have been vaccinated for Neisseria meningitidis 14 days prior to randomisation. | ||
Background therapy | - | ||
Evidence for comparator | No comparator was used in this trial. | ||
Actual start date of recruitment | 16 Dec 2004 | ||
Long term follow-up planned | Yes | ||
Long term follow-up rationale | Safety | ||
Long term follow-up duration | 12 Months | ||
Independent data monitoring committee (IDMC) involvement? | No | ||
| Population of trial subjects | |||
Number of subjects enrolled per country | |||
Country: Number of subjects enrolled | United States: 25 | ||
Country: Number of subjects enrolled | Canada: 1 | ||
Country: Number of subjects enrolled | Australia: 6 | ||
Country: Number of subjects enrolled | Belgium: 3 | ||
Country: Number of subjects enrolled | Germany: 15 | ||
Country: Number of subjects enrolled | Ireland: 2 | ||
Country: Number of subjects enrolled | Italy: 14 | ||
Country: Number of subjects enrolled | Netherlands: 4 | ||
Country: Number of subjects enrolled | Spain: 9 | ||
Country: Number of subjects enrolled | Sweden: 3 | ||
Country: Number of subjects enrolled | Switzerland: 1 | ||
Country: Number of subjects enrolled | United Kingdom: 14 | ||
Worldwide total number of subjects | 97 | ||
EEA total number of subjects | 64 | ||
Number of subjects enrolled per age group | |||
In utero | 0 | ||
Preterm newborn - gestational age | 0 | ||
Newborns (0-27 days) | 0 | ||
Infants and toddlers (28 days-23 months) | 0 | ||
Children (2-11 years) | 0 | ||
Adolescents (12-17 years) | 0 | ||
Adults (18-64 years) | 90 | ||
From 65 to 84 years | 7 | ||
85 years and over | 0 | ||
| |||||||||||
| Recruitment | |||||||||||
Recruitment details | A total of 33 clinical sites in Australia, Belgium, Canada, Germany, Ireland, Italy, Netherlands, Spain, Sweden, Switzerland, United States and the United Kingdom participated and enrolled patients in this study. | ||||||||||
| Pre-assignment | |||||||||||
Screening details | Subjects who had at least one transfusion in the 2 years prior to screening, and were meeting all of the inclusion/exclusion criteria were eligible to enter this study. 107 subjects were screened, 97 were enrolled and received eculizumab. | ||||||||||
| Pre-assignment period milestones | |||||||||||
Number of subjects started | 97 | ||||||||||
Number of subjects completed | 97 | ||||||||||
| Period 1 | |||||||||||
Period 1 title | Treatment Phase (overall period) | ||||||||||
Is this the baseline period? | Yes | ||||||||||
Allocation method | Not applicable | ||||||||||
Blinding used | Not blinded | ||||||||||
Blinding implementation details | Not applicable (open-label study) | ||||||||||
| Arms | |||||||||||
| Arm title | eculizumab | ||||||||||
Arm description | During the Induction Period, patients received 600 mg of eculizumab IV once a week for 4 doses, followed by 900 mg eculizumab IV 1 week later for 1 dose. During the Maintenance Period, patients received 900 mg eculizumab IV every 2 weeks for approximately 24 doses. Each dose was administered by IV infusion over a 25- to 45-minute period. | ||||||||||
Arm type | Experimental | ||||||||||
Investigational medicinal product name | eculizumab | ||||||||||
Investigational medicinal product code | eculizumab | ||||||||||
Other name | Soliris | ||||||||||
Pharmaceutical forms | Concentrate for solution for infusion | ||||||||||
Routes of administration | Intravenous use | ||||||||||
Dosage and administration details | 600 mg of eculizumab once a week for 4 weeks, followed by 900 mg of eculizumab 1 week later for 1 dose, then 900 mg of eculizumab every 2 weeks up through 52 weeks. | ||||||||||
| |||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Baseline characteristics reporting groups | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | eculizumab | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | During the Induction Period, patients received 600 mg of eculizumab IV once a week for 4 doses, followed by 900 mg eculizumab IV 1 week later for 1 dose. During the Maintenance Period, patients received 900 mg eculizumab IV every 2 weeks for approximately 24 doses. Each dose was administered by IV infusion over a 25- to 45-minute period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||
| End points reporting groups | |||
Reporting group title | eculizumab | ||
Reporting group description | During the Induction Period, patients received 600 mg of eculizumab IV once a week for 4 doses, followed by 900 mg eculizumab IV 1 week later for 1 dose. During the Maintenance Period, patients received 900 mg eculizumab IV every 2 weeks for approximately 24 doses. Each dose was administered by IV infusion over a 25- to 45-minute period. | ||
| |||||||||
End point title | Intravascular haemolysis measured by LDH AUC [1] | ||||||||
End point description | A quantitative assessment of haemolysis was obtained by calculating the AUC for LDH from Baseline to Week 52, and the data were analysed using a Wilcoxon signed rank test. | ||||||||
End point type | Primary | ||||||||
End point timeframe | Through week 52 | ||||||||
| 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: This study is a single arm trial and the system did not support statistical analyses for this single arm trial. | |||||||||
| |||||||||
| No statistical analyses for this end point | |||||||||
| |||||||||||||||||||||||||
End point title | Levels of fatigue | ||||||||||||||||||||||||
End point description | The Quality-of-Life (QoL) instrument FACIT-Fatigue scale version 4 was utilised to collect QoL data. The scoring guideline for the FACIT-Fatigue scale version 4 instrument was used to calculate the QoL score; per the corresponding scoring guideline, scores can range from 0 to 52, with higher scores indicating improvement in fatigue. Data reported indicate change of FACIT-Fatigue Scores Between Baseline at several time points. | ||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||
End point timeframe | The FACIT-Fatigue SCALE was administered through 52 weeks. | ||||||||||||||||||||||||
| |||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
| |||||||||||||||||||||||||
End point title | Intravascular haemolysis measured as change in LDH from baseline | ||||||||||||||||||||||||
End point description | Data reported describe change of lactate dehydrogenase (LDH) values from Baseline to selected time points through 52 Weeks. | ||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||
End point timeframe | Through 52 weeks. | ||||||||||||||||||||||||
| |||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Adverse events information | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events | Information regarding AEs was collected from the time the patient signed the informed consent form up to 30 days after the last dose of eculizumab was administered. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type | Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dictionary used for adverse event reporting | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name | MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version | 7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Reporting groups | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | eculizumab | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | - | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| |||
Substantial protocol amendments (globally) | |||
| Were there any global substantial amendments to the protocol? Yes | |||
Date | Amendment | ||
04 Mar 2005 | The purpose of this global amendment was to broaden the study population and to identify a primary surrogate endpoint for efficacy, namely lactate dehydrogenase as area under the curve. | ||
Interruptions (globally) | |||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats | |||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||