Clinical Trial Results:
Pilot study to evaluate the effect of plasma exchange in motor and cognitive function in patients with amyotrophic lateral sclerosis
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Summary
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EudraCT number |
2013-004842-40 |
Trial protocol |
ES |
Global end of trial date |
03 Jun 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
15 Jul 2018
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First version publication date |
15 Jul 2018
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Other versions |
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Summary report(s) |
IG1309 CSR Synopsis |
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 |
IG1309
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02479802 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Instituto Grifols S.A.
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Sponsor organisation address |
Can Guasch 2, Parets del Vallés, Spain, 08150
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Public contact |
Miquel Barceló, Instituto Grifols S.A., 34 935712368, miquel.barcelo@grifols.com
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Scientific contact |
Miquel Barceló, Instituto Grifols S.A., 34 935712368, miquel.barcelo@grifols.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Feb 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
03 Jun 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jun 2016
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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 the study was to evaluate the disease progression using the Amyotrofic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R) score and the Forced Vital Capacity (FVC) of subjects affected by Amyotrophic Lateral Sclerosis (ALS) and treated with Plasma Exchange (PE) with Albutein 5%.
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Protection of trial subjects |
The Investigator obtained a freely given written informed consent from each subject (or his/her legal representative if he/she was disabled) participating in this study, after an appropriate explanation of the aims, methods, anticipated benefits, potential hazards and any other aspect of the study relevant to the subject's decision to participate prior to initiating any study-related procedure to the subject. Subjects were informed of the advantages, risks and constrains of the study and of their right to withdraw at any time. The informed consent form was signed, with name and date noted by the subject, before the subject (or his/her representative) was exposed to any study-related procedure, including screening tests for eligibility.
The Investigator ensured that the subject's anonymity was preserved. On CRFs or any other documents submitted to the Sponsor, the subjects were not identified by their names, but by an identification code. Documents not for submission to the Sponsor, i.e. the confidential subject identification code, original consent forms and source records were maintained by the Investigator in strict confidence.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Nov 2014
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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 |
Spain: 13
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Worldwide total number of subjects |
13
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EEA total number of subjects |
13
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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) |
12
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
The enrolled population, that is, all recruited subjects who provided written informed consent to participate, was composed of 13 (100%) subjects. Originally, the planned enrollment was 10 subjects, but 3 additional subjects were recruited to achieve 10 fully eligible subjects. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects of both gender, older than 18 and younger than 70 years of age, who had an ALS diagnosis and FVC >70% and who gave their signed written consent to participate were included in the study. 13 subjects were screened and enrolled in the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Overall study | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Plasma exchange with Albumin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Albutein 5%
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Investigational medicinal product code |
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Other name |
Human Albumin 5%
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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 |
27 plasma exchange procedures using Albumin 5% (estimated 3000 mL per plasma exchange) as replacement solution:
- three weeks of intensive treatment with two plasma exchanges per week
- twenty-one weeks of maintenance treatment with one weekly plasma exchange
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Arm title
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Visit 0 (Week 0) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Baseline visit | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Albutein 5%
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Investigational medicinal product code |
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Other name |
Human Albumin 5%
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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 |
27 plasma exchange procedures using Albumin 5% (estimated 3000 mL per plasma exchange) as replacement solution:
- three weeks of intensive treatment with two plasma exchanges per week
- twenty-one weeks of maintenance treatment with one weekly plasma exchange
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Arm title
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Visit 1 (Week 4) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Evaluation visit at end of Intensive treatment period | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Albutein 5%
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Investigational medicinal product code |
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Other name |
Human Albumin 5%
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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 |
27 plasma exchange procedures using Albumin 5% (estimated 3000 mL per plasma exchange) as replacement solution:
- three weeks of intensive treatment with two plasma exchanges per week
- twenty-one weeks of maintenance treatment with one weekly plasma exchange
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Arm title
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Visit 2 (Week 12) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Evaluation vist in the middle of treatment phase | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Albutein 5%
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Investigational medicinal product code |
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Other name |
Human Albumin 5%
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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 |
27 plasma exchange procedures using Albumin 5% (estimated 3000 mL per plasma exchange) as replacement solution:
- three weeks of intensive treatment with two plasma exchanges per week
- twenty-one weeks of maintenance treatment with one weekly plasma exchange
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Arm title
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Visit 4 (Week 25) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Evaluation visit one week after the end of treatment phase, start of follow-up phase | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Albutein 5%
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Investigational medicinal product code |
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Other name |
Human Albumin 5%
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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 |
27 plasma exchange procedures using Albumin 5% (estimated 3000 mL per plasma exchange) as replacement solution:
- three weeks of intensive treatment with two plasma exchanges per week
- twenty-one weeks of maintenance treatment with one weekly plasma exchange
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Arm title
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Visit 5 (Week 36) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Evaluation visit in the middle of Follow-up phase | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Albutein 5%
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Investigational medicinal product code |
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Other name |
Human Albumin 5%
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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 |
27 plasma exchange procedures using Albumin 5% (estimated 3000 mL per plasma exchange) as replacement solution:
- three weeks of intensive treatment with two plasma exchanges per week
- twenty-one weeks of maintenance treatment with one weekly plasma exchange
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Arm title
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Visit 6 (Week 48) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm description |
Final visit - end of follow-up phase or early withdrawal visit | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Albutein 5%
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Investigational medicinal product code |
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Other name |
Human Albumin 5%
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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 |
27 plasma exchange procedures using Albumin 5% (estimated 3000 mL per plasma exchange) as replacement solution:
- three weeks of intensive treatment with two plasma exchanges per week
- twenty-one weeks of maintenance treatment with one weekly plasma exchange
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Overall study
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Reporting group description |
Plasma exchange with Albumin | ||
Reporting group title |
Visit 0 (Week 0)
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Reporting group description |
Baseline visit | ||
Reporting group title |
Visit 1 (Week 4)
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Reporting group description |
Evaluation visit at end of Intensive treatment period | ||
Reporting group title |
Visit 2 (Week 12)
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Reporting group description |
Evaluation vist in the middle of treatment phase | ||
Reporting group title |
Visit 4 (Week 25)
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Reporting group description |
Evaluation visit one week after the end of treatment phase, start of follow-up phase | ||
Reporting group title |
Visit 5 (Week 36)
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Reporting group description |
Evaluation visit in the middle of Follow-up phase | ||
Reporting group title |
Visit 6 (Week 48)
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Reporting group description |
Final visit - end of follow-up phase or early withdrawal visit | ||
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End point title |
Changes From Baseline in the ALS Functional Rating Scale Revised (ALSFRS-R) [1] | ||||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Weeks 4, 12, 25, 36, and 48
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| Notes [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This is a single arm study, arm reported in the Overall study period are different time points where assessments were made. For this particular endpoint, a statistical analysis is only present from baseline and final visit. |
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Statistical analysis title |
Change from Baseline at Week 48 | ||||||||||||||||||||||||||||
Comparison groups |
Visit 6 (Week 48) v Visit 0 (Week 0)
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Number of subjects included in analysis |
24
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Analysis specification |
Pre-specified
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Analysis type |
[2] | ||||||||||||||||||||||||||||
P-value |
< 0.0001 | ||||||||||||||||||||||||||||
Method |
t-test, 1-sided | ||||||||||||||||||||||||||||
Confidence interval |
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| Notes [2] - Statistical comparison of primary endpoint changes from baseline vs. final visit (week 48) data. Both arms are not mutually exclusive, so the total subjects in this analysis is just 13 subjects. The system does not allow single-arm comparison, this is the only way to include statistical analysis regarding changes in time. |
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End point title |
Change From Baseline in Forced Vital Capacity (FVC) [3] | ||||||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Weeks 4, 12, 25, 36, and 48
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| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This is a single arm study, arm reported in the Overall study period are different time points where assessments were made. For this particular endpoint, a statistical analysis is only present from baseline and final visit. |
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Statistical analysis title |
Change from Baseline at Week 48 | ||||||||||||||||||||||||||||
Comparison groups |
Visit 6 (Week 48) v Visit 0 (Week 0)
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Number of subjects included in analysis |
24
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Analysis specification |
Pre-specified
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Analysis type |
[4] | ||||||||||||||||||||||||||||
P-value |
= 0.0006 | ||||||||||||||||||||||||||||
Method |
t-test, 1-sided | ||||||||||||||||||||||||||||
Confidence interval |
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| Notes [4] - Statistical comparison of primary endpoint changes from baseline vs. final visit (week 48) data. Both arms are not mutually exclusive, so the total subjects in this analysis is just 13 subjects. The system does not allow single-arm comparison, this is the only way to include statistical analysis regarding changes in time. |
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End point title |
Changes From Baseline in ALS Cognitive Function Determined by the ALS-Cognitive Behavioral Screen (ALS-CBS) Test [5] | |||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Weeks 25 and 48
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| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This is a single arm study, arm reported in the Overall study period are different time points where assessments were made. For this particular endpoint, a general assessment was performed only at Visit 4 (Week 25) and Visit 6 (Week 48), so not all the arms (time points) have results data. |
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| No statistical analyses for this end point | ||||||||||||||||||||||
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End point title |
Motor Evoked Potential in Thenar and Hypothenar Eminence, and Anterior Tibialis Muscle [6] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Weeks 0, 4, 12, 25, 36, and 48
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| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This is a single arm study, arm reported in the Overall study period are different time points where assessments were made. For this particular endpoint, overall study arm had not result data. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Changes From Baseline in ALS Assessment Questionnaire 40 (ALSA-Q40). [7] | ||||||||||||||||||||||||
End point description |
The transformed scores are presented that use an index from 0 to 100 for each dimension to allow for straightforward interpretation of the results.
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End point type |
Secondary
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End point timeframe |
Weeks 25 and 48
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| Notes [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This is a single arm study, arm reported in the Overall study period are different time points where assessments were made. For this particular endpoint, a general assessment was performed only at Visit 4 (Week 25) and Visit 6 (Week 48), so not all the arms (time points) have results data. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percentage of Plasma Exchange Sessions Associated With One Adverse Event or Adverse Reaction, Including Clinically Significant Changes in Vital Signs or Lab Parameters [8] | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
During the Treatment Phase (24 weeks)
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| Notes [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: This is a single arm study, arm reported in the Overall study period are different time points where assessments were made. For this particular endpoint, a general assessment was performed at the end of treatment phase, so not all the arms (time points) have results data. |
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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 |
Adverse events were collected throughout the study (48 weeks).
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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 |
17.0
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Reporting groups
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Reporting group title |
Overall study
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Reporting group description |
Plasma exchange with Albumin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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29 May 2014 |
This amendment included the following changes relevant to the conduct of the study:
˗ Modification of Secondary efficacy variables:
- Neuropsychological tests and clinical criteria such as the Neary criteria for frontotemporal dementia were removed from the protocol. Therefore, each subject’s cognitive function would be evaluated solely with the ALS-CBS (Amyotrophic Lateral Sclerosis - Cognitive Behavioral Screen) test to better align with standard clinical practice procedures of the site.
- The motor evoked potential variable determined by electromyography was redefined to follow the standard clinical practice procedures of the site.
- The study visit dates for biomarker measurements (oxidative stress, inflammation and functional capacity of plasma albumin) were changed from Visit 4 (Week 25) to Visit 3 (Week 24 coinciding with PE#27). This way, biomarker samples could be obtained prior and after PE#27.
˗ The numbers of laboratory tests were reduced following the medical criteria of the site’s apheresis experts. Therefore, safety blood count and coagulation tests were no longer included in each PE and only scheduled at Baseline visit (before the first PE), at Visit 1 (Week 4 coinciding with PE#7, which is the evaluation visit after the end of the intensive phase of treatment [PE#1 to PE#6]), at Visit 5 (Week 36 during Follow-up) and at Final visit 6 (Week 48).
˗ Additionally, a lipid profile test was added, as it is routine clinical practice in the Multidisciplinary Unit ELA Bellvitge University Hospital |
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17 Oct 2014 |
This amendment included the following changes relevant to the conduct of the study:
- Some discrepancies between protocol section 6.2.1 Study Chronogram and Appendix 1 Study Procedure Flow-Chart were detected. Therefore, coagulation tests and blood count from V5 visit were eliminated. In addition, metabolomics biomarkers assessments were removed from Visit 5 and Visit 6 and metabolomics biomarkers tests were limited to visits V0, V2 and V3.
- The minimum blood volume extracted for biomarker analysis was added. Total blood volume to be extracted was increased in order to be able to analyze all planned biomarkers (oxidative stress, inflammation and non-directed metabolomic profile). |
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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 | |||
