Clinical Trial Results:
A prospective, multicentre, open label, exploratory study to investigate the ability of the Heidelberg Assay Panel and the B-Cell /Antibody response panel to predict the clinical effect of Octagam 5% in subjects with relapsing/remitting (RR) multiple sclerosis (MS).
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Summary
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EudraCT number |
2008-004579-22 |
Trial protocol |
AT DE |
Global end of trial date |
21 Dec 2010
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Dec 2016
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First version publication date |
31 Dec 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 |
GAM-25
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Additional study identifiers
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ISRCTN number |
ISRCTN57377482 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Octapharma AG
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Sponsor organisation address |
Seidenstrasse 2, Lachen, Switzerland, CH-8853
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Public contact |
Clinical Research Department, Octapharma Pharmazeutika Prod.Ges.m.b.H, 0043 161032-0,
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Scientific contact |
Clinical Research Department, Octapharma Pharmazeutika Prod.Ges.m.b.H, 0043 161032-0,
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Aug 2012
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Dec 2010
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
No primary objective has been chosen, as the study was an exploratory study to identify biomarkers that could be predictive for the clinical response to IVIG treatment in patients with RR-MS.
Objective was to investigate :
-whether any parameters of the HAP correlate with the clinical effect observed following Octagam 5% treatment in subjects with relapsing-remitting MS and whether any B-cell/antibody responses correlate with the clinical effect observed following Octagam 5% treatment in subjects with RR MS.
- the proportion of subjects responding to Octagam 5% treatment vs. subjects not responding and the relapse activity during the observation period.
- efficacy as assessed by neurological examinations using the Expanded Disability Status Scale (EDSS) and Functional System (FS) and the Multiple Sclerosis Functional Composite measure (MSFC).
- the change of T2/T1 lesion load and active lesions as demonstrated by contrast enhancement on (MRI)
-tolerability of Octagam 5%
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Protection of trial subjects |
This trial was conducted in accordance to the principles of GCP, ensuring that the rights, safety and well-being of patients are protected and in consistency with the Declaration of Helsinki. Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and risk factors associated with the investigational medicinal product. Throughout the study safety was assessed, such as occurrence of AEs, safety labs, vital signs and physical/neurological examinations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Mar 2009
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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 |
Austria: 13
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Country: Number of subjects enrolled |
Germany: 20
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Worldwide total number of subjects |
33
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EEA total number of subjects |
33
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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) |
0
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Adults (18-64 years) |
33
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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 |
- | ||||||||||
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Pre-assignment
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Screening details |
Patients with RR-MS with an EDSS between 0 and 3.5 (0 to 3.5) for whom first-line disease-modifying treatments were either contraindicated or not tolerated and who did not have any contraindications for IVIG therapy were eligible to take part in the study. | ||||||||||
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Period 1
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Period 1 title |
Overall Trial (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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Octagam 5% | ||||||||||
Arm description |
Open-label arm of RR-MS patients who had to be treated with 0.4 g/kg Octagam 5% for 20 infusions in 4-week (+/- 1 week) intervals. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Octagam 5%, Human normal immunoglobulin 5%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
A total of 20 intravenous infusions of 0.4 g/kg in 4-week (±1 week) intervals per patient
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Baseline characteristics reporting groups
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Reporting group title |
Overall Trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Octagam 5%
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Reporting group description |
Open-label arm of RR-MS patients who had to be treated with 0.4 g/kg Octagam 5% for 20 infusions in 4-week (+/- 1 week) intervals. | ||
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End point title |
No primary objective as the study was an exploratory study [1] | ||||||
End point description |
No primary objective has been chosen, as the study was an exploratory study to identify biomarkers that could be predictive for the clinical response to IVIG treatment in patients with RR-MS.
All data collected were summarised by means of descriptive statistics to be understood in the exploratory sense; no confirmatory hypothesis testing was planned. Due to the exploratory nature of the study no sample size calculation was done.
Because of the early termination of the study due to safety concerns that arose from post-marketing data, none of the patients, except one completed the study with all Octagam 5% infusions as planned.
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End point type |
Primary
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End point timeframe |
total study
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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: All data collected were summarised by means of descriptive statistics to be understood in the exploratory sense; no confirmatory hypothesis testing was planned. Due to the exploratory nature of the study no sample size calculation was done. |
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| Notes [2] - study exloratory only, analyses not applicable |
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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 |
Throughout the study, patients were monitored for AEs.
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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 |
12.0
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Reporting groups
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Reporting group title |
Octagam 5%
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Reporting group description |
AEs in more that 1 patient | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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07 Mar 2009 |
Amendment 1 (main changes):
According to results of further pre-study investigations, it was decided to delete some of the originally described HAP parameters.
It was not clearly differentiated between stimulation and ex vivo incubation of blood samples. It mentioned “IVIG” for incubation of blood samples. The wording was specified. “IVIG” was replaced by “Octagam 5%”.
Laboratory methods to determine the parameters were amended.
Serum parameters were defined as BARP endpoint and EDTA blood samples were to be tested only from patients of the Innsbruck study site.
An increase of the EDSS of at least 1 step was defined as non-response within this study. It was agreed that a continuous increase of EDSS of at least 2 steps without an underlying relapse had to be considered as a switch of the disease to the secondary progressive form and that those patients had to be withdrawn from the study.
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26 Aug 2009 |
Amendment 2 (main changes):
The time frame for baseline investigations was extended from 1 week to 2 weeks.
Bicarbonate was deleted from the clinical chemistry parameters to be assessed.
The duration of the study was prolonged from 18 to 24 months.
In accordance with new Octapharma drug safety Standard Operating Procedures (SOPs), a few updates were made to the protocol safety section.
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23 Nov 2009 |
Amendment 3 (main changes):
The study was prolonged from 48 weeks to 80 weeks to increase the diagnostic value of the study markedly and to enhance the chances to differentiate clinical responders from non-responders.
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27 Sep 2010 |
Amendment 4 (main changes):
The study duration was prolonged to 1st quarter of 2012.
Exclusion criterion No. 16 was clarified: Participation in another clinical study involving an IMP was not allowed. However, studies comprising data or blood sampling collections on a regular or long-term basis are exempt from this exclusion.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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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 | |||||||
