Clinical Trial Results:
AN OPEN-LABEL MULTI-CENTER STUDY OF ECULIZUMAB IN CHILDREN AND ADOLESCENTS WITH A DIAGNOSIS OF PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA
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Summary
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EudraCT number |
2009-010402-11 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
12 May 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Aug 2016
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First version publication date |
06 Aug 2016
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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 |
M07-005
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00867932 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Alexion Pharmaceuticals Incorporated
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Sponsor organisation address |
100 College Street, New Haven, United States, CT 06410
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Public contact |
European Clinical Trial Information, Alexion Europe SAS, + 33 1 47 10 06 06, clinicaltrials.eu@alxn.com
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Scientific contact |
European Clinical Trial Information, Alexion Europe SAS, + 33 1 47 10 06 06, clinicaltrials.eu@alxn.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-000876-PIP01-10 | ||
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 |
04 Nov 2011
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 May 2011
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Global end of trial reached? |
Yes
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Global end of trial date |
12 May 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 |
The primary objective of Study M07-005 was to evaluate the PK and PD parameter estimates of eculizumab to confirm the dose regimens for paediatric patients with PNH
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Protection of trial subjects |
Patients must have been vaccinated against Neisseria meningitidis, Pneumococcus species, and Hemophilus influenzae type b at least 14 days prior to the start of study drug, or be vaccinated and receive treatment with appropriate antibiotics until 14 days after vaccination. Patients were excluded for prior treatment with eculizumab, presence or suspicion of bacterial infection or recurrent bacterial infections, or history of meningococcal, pneumococcal, or gonococcal disease. Patients were also excluded if pregnant, breastfeeding, or intending to conceive during the study period.
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Background therapy |
No background therapy was used in this trial. | ||
Evidence for comparator |
No comparator was used in this trial. | ||
Actual start date of recruitment |
02 Oct 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United States: 7
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Worldwide total number of subjects |
7
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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) |
1
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Adolescents (12-17 years) |
6
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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 |
Recruitment period lasted from October 2009 to January 2011. Three sites in the USA enrolled a total of 7 patients. | ||||||||||
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Pre-assignment
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Screening details |
Screening phase was approx. 2 weeks. ICF and paediatric/adolescent assent forms were signed at or before Visit 1. Inclusion/exclusion criteria were obtained and evaluated. If all screening criteria are met, the patient was eligible to enter the treatment phase of the study after receiving a N. meningitidis, pneumococcus and hemophilus vaccination | ||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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eculizumab | ||||||||||
Arm description |
All 7 patients enrolled in the trial received eculizumab. There is no other arm in the trial. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
eculizumab
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Investigational medicinal product code |
eculizumab
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Other name |
Soliris
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
- If weight ≥30 kg:
Induction loading: 600mg weekly x 4
Maintenance: 900mg Wk5; 900mg Q2wks
- If weight 20 - <30kg:
Induction/loading: 600mg weekly x 2
Maintenance: 600mg Wk3; 600mg Q2wks
- If weight 10 - <20kg:
Induction/loading: 600mg weekly x 1
Maintenance: 300mg Wk2; 300mg Q2wks
- If weight 5 – <10 kg:
Induction/loading: 300 mg Weekly for 1 Week
Maintenance: 300mg Wk2; 300mg Q3wks
Eculizumab was administered via a 35 minutes (+/-10 minutes) intravenous infusion.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
Seven patients aged 11–17 years were enrolled between October 2009 and January 2011; younger patients did not present for eligibility screening at the participating centers during the study period. All patients entered the body weight cohort of greater or equal to 30 kg. Each patient received all nine doses of eculizumab via peripheral vein and completed the study period of 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
eculizumab
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Reporting group description |
All 7 patients enrolled in the trial received eculizumab. There is no other arm in the trial. | ||
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End point title |
PK and PD evaluation [1] | ||||||||||||
End point description |
PD response was measured by the capacity of patient serum to lyse chicken erythrocytes in a human serum-complement hemolytic assay; complete complement blockade was defined as <20% hemolysis in vitro. All baseline trough plasma levels of eculizumab were undetectable. Peak and trough eculizumab concentrations increased gradually and reached a plateau by week 4. At week 12, median trough eculizumab levels were 192.5 mcg/ml (range 124.2-321.1) and median peak levels were 425.4 mcg/ml (range 220.5-556.1). The max and min conc. of eculizumab, and AUC were significantly associated with the change from baseline in LDH at the follow-up visits (P=0.0273, P=0.0250 and P=0.0263 respectively). Prior start of eculizumab, in vitro hemolysis of <20%, that is, inducing complete complement blockade, after steady-state levels were reached at week 4.
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End point type |
Primary
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End point timeframe |
PK ad PD samples were collected before and after completing the administration of eculizumab at each visit.
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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: This study is a single arm trial and the system did not support statistical analyses for this single arm trial. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Safety | ||||||||||||||||||||||||||||
End point description |
Examination of treatment-emergent adverse events
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End point type |
Secondary
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End point timeframe |
12 weeks
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Efficacy - Mean change of LDH from baseline at week 12 | ||||||||||
End point description |
The area under the curve (AUC) for the change of LDH from baseline (week 0 to week 12) was also calculated.
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End point type |
Secondary
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End point timeframe |
12 weeks
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| No statistical analyses for this end point | |||||||||||
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End point title |
Efficacy - Mean Plasma-free Haemoglobin | ||||||||||||
End point description |
Plasma-free haemoglobin levels were analyzed at 12 weeks.
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End point type |
Secondary
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End point timeframe |
12 weeks
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Efficacy - LDH values and change of LDH from baseline | ||||||||||||||||||||
End point description |
Efficacy summary of LDH values and change of LDH from baseline.
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End point type |
Secondary
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End point timeframe |
12 weeks
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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 |
From the time patient signs the informed consent form up to 8 weeks after last dose of eculizumab
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Adverse event reporting additional description |
Treatment-emergent adverse events (TEAEs) that occurred in at least 2 subjects during the study are reported here. TEAEs are defined as an event not present prior to exposure to eculizumab or any event already present that worsens in either intensity or frequency following exposure to eculizumab.
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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 |
13.0
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Reporting groups
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Reporting group title |
All participating patients in the trial
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Reporting group description |
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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? Yes | |||
Date |
Amendment |
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03 Nov 2010 |
Amendment 2 (protocol v3.0): Modify the protocol to restrict inclusion criteria as agreed in the Paediatric Investigation Plan for eculizumab.
Further to the evaluation of the Paediatric Investigation Plan for eculizumab by the European Paediatric Committee, the protocol inclusion criteria was modified as follows:
1. To update dosing for patients 2 - 17 years old and weight ≥5kg.
2. To include vaccination requirements previously described in the methodology section of the protocol as an inclusion requirement. In addition, to add vaccination requirements for Pneumococci and Haemophilus.
3. To only include paediatric patients in whom haemolysis contributes to the anaemia.
4. To not include patients with history of meningococcal/pneumococcal/gonococcal disease.
5. To add an external data monitoring committee (DMC) to monitor safety.
6. To add an exploratory endpoint to assess correlation between LDH and PNH clone size. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/24777716 |
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