Clinical Trial Results:
A single-centre, open single-arm study where the safety, tolerability and efficacy of subcutaneously administered ILB will be evaluated in patients with Amyotrophic Lateral Sclerosis
Summary
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EudraCT number |
2017-005065-47 |
Trial protocol |
SE |
Global end of trial date |
20 Aug 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Sep 2020
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First version publication date |
05 Sep 2020
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Other versions |
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 |
TM-105
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03613571 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
TikoMed AB
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Sponsor organisation address |
Box 81, Viken, Sweden, 26303
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Public contact |
Lars Bruce, TikoMed AB, +46 707238414, florence.lange@tikomed.com
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Scientific contact |
Lars Bruce, TikoMed AB, +46 707238414, florence.lange@tikomed.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 |
16 Oct 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
20 Aug 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Aug 2019
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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 |
To study safety and tolerability of subcutaneously administered ILB in patients diagnosed with ALS.
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Protection of trial subjects |
The study was performed in accordance with the ethical principles that have their origin in the Declaration of Helsinki that are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)/Good Clinical Practice (GCP) and applicable regulatory requirements. Informed consent was obtained from all patients prior to initiation of the study. Protocol deviations related to GCP that were reported during the study are discussed further in the section "More information".
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Background therapy |
No background therapy was used in the trial. | ||
Evidence for comparator |
There was no comparator used in this study. There was 1 treatment group that received the test product. | ||
Actual start date of recruitment |
17 Sep 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 |
Sweden: 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) |
9
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
Screening was performed 30 days prior to treatment. The first patient screened was on 2018-09-17. It was planned to include 15 patients in the study, however due to delays in recruitment and the fact that no safety concerns were reported, it was decided by the Sponsor to terminate patient recruitment and conclude the study with 13 patients | ||||||||
Pre-assignment
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Screening details |
Twenty patients were screened 13 were included and treated. The reasons for screening failure were: not fulfilment of inclusion/exclusion criteria and death before study start. All 13 patients were included in the analysis. One patient did not attend the last follow-up visit due to ALS progression. A total of 12 patients completed the study. | ||||||||
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 | ||||||||
Blinding implementation details |
Not applicable (open-label study)
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Arms
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Arm title
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ILB treatment group | ||||||||
Arm description |
- | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
ILB
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Investigational medicinal product code |
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Other name |
The active pharmaceutical ingredient is a low molecular weight dextran sulfate (LMW-DS, approx. 20 % sulfate, mean MW 5 kDa)
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
There was only 1 treatment group in the study (ILB treatment group). The dose administered (1 mg/kg) depended on the patient’s body weight at Visit 2, prior to the first ILB administration.
The ILB was administered in single short term subcutaneous injections on alternative sides of the abdomen, thigh or buttock, in that order of priority. The maximum volume injected at each injection site was approximately 2 mL and the number of injections per patient could range between 1 and 3 sites depending on the volume to be injected. Each administration occurred within ±3 days from the pre-defined dosing days (Days 1, 8, 15, 22 and 29) with at least 4 days between 2 IMP administrations. ILB administration was performed by the study personnel and patients were observed for at least 3 hours after the injection.
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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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Subject analysis sets
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Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The safety analysis set was defined as patients who received any dose of the test product (ILB)
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Defined as all patients who received at least 1 dose of the test product (ILB) and with at least 1 efficacy measurement
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Subject analysis set title |
Per protocol analysis set
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Defined as all patients who received at least 1 dose of the test product (ILB) and with at least 1 efficacy measurement. This analysis set was the same as the full analysis set.
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Subject analysis set title |
Results at baseline
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This sub-group consists of the same subjects as the safety analysis set and the full analysis set. The sub-group was created to present the statistical analysis of changes from baseline in this single-arm study. The total number of subjects in the analysis is 13.
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Subject analysis set title |
Results at post-treatment visits
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This sub-group consists of the same subjects as the safety analysis set and the full analysis set. The sub-group was created to present the statistical analysis of changes from baseline in this single-arm study. The total number of subjects in the analysis is 13.
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Subject analysis set title |
TEAEs during the treatment period
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
TEAEs that occurred during the treatment period are reported using this group. This group consisted of the same subjects as in the Safety analysis set (N=13).
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Subject analysis set title |
TEAEs during the follow-up period
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
TEAEs that occurred during the follow-up period are reported using this group. This group consisted of the same subjects as in the Safety analysis set (N=13).
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Subject analysis set title |
Safety analysis set - copy
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This is not a separate subgroup of subjects but contains data for the same 13 subjects as in the safety analysis set.
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End points reporting groups
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Reporting group title |
ILB treatment group
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Reporting group description |
- | ||
Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety analysis set was defined as patients who received any dose of the test product (ILB)
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Subject analysis set title |
Full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Defined as all patients who received at least 1 dose of the test product (ILB) and with at least 1 efficacy measurement
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Subject analysis set title |
Per protocol analysis set
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Defined as all patients who received at least 1 dose of the test product (ILB) and with at least 1 efficacy measurement. This analysis set was the same as the full analysis set.
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Subject analysis set title |
Results at baseline
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
This sub-group consists of the same subjects as the safety analysis set and the full analysis set. The sub-group was created to present the statistical analysis of changes from baseline in this single-arm study. The total number of subjects in the analysis is 13.
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Subject analysis set title |
Results at post-treatment visits
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
This sub-group consists of the same subjects as the safety analysis set and the full analysis set. The sub-group was created to present the statistical analysis of changes from baseline in this single-arm study. The total number of subjects in the analysis is 13.
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Subject analysis set title |
TEAEs during the treatment period
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
TEAEs that occurred during the treatment period are reported using this group. This group consisted of the same subjects as in the Safety analysis set (N=13).
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Subject analysis set title |
TEAEs during the follow-up period
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
TEAEs that occurred during the follow-up period are reported using this group. This group consisted of the same subjects as in the Safety analysis set (N=13).
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Subject analysis set title |
Safety analysis set - copy
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
This is not a separate subgroup of subjects but contains data for the same 13 subjects as in the safety analysis set.
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End point title |
Frequency, seriousness and intensity of Treatment-emergent Adverse Events [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
A Treatment-emergent Adverse Event (TEAE) was defined as any AE not present prior to the initiation of IMP administration or any event already present that worsened in either intensity or frequency following exposure to the IMP. A serious AE (SAE) was defined as any untoward medical occurrence that at any dose:
• Resulted in death
• Was life-threatening
• Required inpatient hospitalization or prolongation of existing hospitalization
• Resulted in persistent or significant disability/incapacity, or
• Was a congenital anomaly/birth defect
All AEs and SAEs were recorded from start of IMP administration until the end of follow-up (Visit 9). Adverse events that occurred before first IMP treatment were reported separately as baseline events.
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End point type |
Primary
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End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
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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 "Frequency, seriousness and intensity of Treatment-emergent Adverse Events" was only analyzed descriptively in this study. No statistical analyses were performed. |
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Notes [2] - This is not a separate analysis set but reports data for the same 13 subjects as during treatment. |
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No statistical analyses for this end point |
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End point title |
Physical examination [3] | ||||||||||||||||
End point description |
A complete physical examination included assessments of the head, eyes, ears, nose, throat, cardiac, peripheral vascular, pulmonary, musculoskeletal, neurologic, abdominal, lymphatic and dermatologic functions. Abnormal findings were specified and presented by patient and summarised in frequency tables. No statistical analysis was performed.
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End point type |
Primary
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End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
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Notes [3] - 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 "Physical examination" was only analyzed descriptively in this study. No statistical analyses were performed. |
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Notes [4] - This is not a separate analysis set but contains the same 13 subjects as the safety analysis set. |
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No statistical analyses for this end point |
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End point title |
Vital signs-blood pressure | ||||||||||||||||||||||||||||||||
End point description |
Diastolic and systolic blood pressure was measured in supine position after 5 minutes of rest using the same method each time. Data were presented by visit for each parameter and patient and summarised using summary statistics, including absolute and percent change from baseline. The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 2).
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End point type |
Primary
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End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
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Notes [5] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
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Statistical analysis title |
No change in blood pressure | ||||||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the safety analysis set to assess the statistical significance of changes from baseline.
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Comparison groups |
Results at baseline v Results at post-treatment visits
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Number of subjects included in analysis |
26
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Analysis specification |
Pre-specified
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Analysis type |
other [6] | ||||||||||||||||||||||||||||||||
P-value |
> 0.05 [7] | ||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||
Notes [6] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [7] - There was no statistically significant change in blood pressure during the study. |
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End point title |
Vital signs- heart rate | ||||||||||||||||||||||||||||
End point description |
Heart rate was measured in supine position after 5 minutes of rest using the same method each time. Data were presented by visit for each parameter and patient and summarised using summary statistics, including absolute and percent change from baseline. The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 2).
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End point type |
Primary
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End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
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Notes [8] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
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Statistical analysis title |
No change in heart rate | ||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the safety analysis set to assess the statistical significance of changes from baseline.
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Comparison groups |
Results at post-treatment visits v Results at baseline
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Number of subjects included in analysis |
26
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Analysis specification |
Pre-specified
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Analysis type |
other [9] | ||||||||||||||||||||||||||||
P-value |
> 0.05 [10] | ||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
Notes [9] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [10] - There was no statistically significant change in heart rate during the study. |
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End point title |
Electrocardiogram recordings | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Single 12-lead electrocardiogram (ECG)was recorded after 10 minutes of supine rest using an ECG machine. PQ/PR, QRS, QT and QTcH intervals were recorded. All ECG data were listed for each patient and summarised as vital signs parameters. The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 1a).
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End point type |
Primary
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End point timeframe |
Visit 1a (screening) and Visit 7( day 36, follow-up)
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Notes [11] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
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Statistical analysis title |
No change in ECG parameters | ||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the safety analysis set to assess the statistical significance of changes from baseline.
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Comparison groups |
Results at baseline v Results at post-treatment visits
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Number of subjects included in analysis |
26
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Analysis specification |
Pre-specified
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Analysis type |
other [12] | ||||||||||||||||||||||||||||||||||||||||||||||||
P-value |
> 0.05 [13] | ||||||||||||||||||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||
Notes [12] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [13] - There was no statistically significant change in any of the ECG parameters from baseline to Visit 7 ( first follow-up) |
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End point title |
Vital signs-body temperature | ||||||||||||||||||||||||
End point description |
Body temperature was measured in supine position after 5 minutes of rest using the same method each time. The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 2). Data were presented by visit for each parameter and patient and summarised using summary statistics, including absolute and percent change from baseline (Visit 2).
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End point type |
Primary
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End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
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Notes [14] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
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Statistical analysis title |
No change in body temperature | ||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the safety analysis set to assess the statistical significance of changes from baseline.
|
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Comparison groups |
Results at baseline v Results at post-treatment visits
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Number of subjects included in analysis |
26
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Analysis specification |
Pre-specified
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Analysis type |
other [15] | ||||||||||||||||||||||||
P-value |
> 0.05 [16] | ||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Notes [15] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [16] - There was no statistically significant change in body temperature during the study |
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End point title |
Clinical chemistry parameters | ||||||||||||||||||||||||||||||||
End point description |
Clinical chemistry parameters assessed:
Sodium
Potassium
Chloride
Calcium
Albumin
Aspartate aminotransferase (AST)
Alkaline Phosphatase
Alanine aminotransferase (ALT)
Creatinine
Creatinine kinase
Myoglobin
C-reactive protein (CRP)
Total bilirubin
Glucose (non-fasting)
Data were presented by visit for each parameter and patient and summarised using summary statistics, including absolute and percent change from baseline (Visit 2). The overall significance level was 5%.
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End point type |
Primary
|
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End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
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Notes [17] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
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Statistical analysis title |
Changes in clinical chemistry parameters | ||||||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the safety analysis set to assess the statistical significance of changes from baseline.
|
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Comparison groups |
Results at baseline v Results at post-treatment visits
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Number of subjects included in analysis |
26
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Analysis specification |
Pre-specified
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Analysis type |
other [18] | ||||||||||||||||||||||||||||||||
P-value |
< 0.05 [19] | ||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||
Notes [18] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [19] - Statistically significant mean changes from baseline: bilirubin (Visit 5), creatinine (Visit 6), myoglobin (Visit 7) and glucose (Visit 8). |
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End point title |
Haematology | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Haematological parameters assessed:
Haemoglobin (Hb)
Haemoglobin S (only at screening)
Haemoglobin A1c (only at screening)
Red blood cells (RBC)
White blood cells (WBC)
Differential cell count
Platelets (thrombocytes)
Data were presented by visit for each parameter and patient and summarised using summary statistics, including absolute and percent change from baseline (Visit 2). The overall significance level was 5%.
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End point type |
Primary
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End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
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Notes [20] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
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Statistical analysis title |
Changes in haematological parameters | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the safety analysis set to assess the statistical significance of changes from baseline.
|
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Comparison groups |
Results at baseline v Results at post-treatment visits
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Number of subjects included in analysis |
26
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Analysis specification |
Pre-specified
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Analysis type |
other [21] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 [22] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Notes [21] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [22] - There were statistically significant relative changes in Hb (Visits 6 and 7), erythrocytes (Visits 6, 7 and 9), leukocytes (Visit 8), platelets (Visit 5), lymphocytes (Visits 5 and 7) and neutrophils (Visit 8). |
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End point title |
Haemostatic parameters | ||||||||||||||||||||||||||||
End point description |
Haemostatic parameters assessed:
Effect activated partial thromboplastin time (APTT): Visit 1a, Visit 2 and Visit 6 (15 min pre-dose, 30 min post-dose, 1 hour post-dose, 2 hours post-dose, 2.5 hours post-dose, 3 hours post-dose, 4 hours post-dose and 6 hours post-dose)
Fibrinogen: Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
Von Willebrand factor (vW antigen, vW activity + factor VIII): Visit 1a (screening)
Prothrombin intl. normalized ratio (PK-INR): Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
Data were presented by patient and assessment time as changes from baseline, using summary statistics. The overall significance level was 5%. Statistics were presented for all factors except APTT.
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End point type |
Primary
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End point timeframe |
APTT: Visit 1a (screening), Visit 2 (day 1 of treatment) and Visit 6 (day 29 of treatment)
Fibrinogen and PK-INR: total study
Von Willebrand factor :Visit 1a (screening)
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Attachments |
Untitled (Filename: APTT.docx) |
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Notes [23] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
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Statistical analysis title |
Changes in haemostatic parameters | ||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the safety analysis set to assess the statistical significance of changes from baseline.
|
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Comparison groups |
Results at baseline v Results at post-treatment visits
|
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Number of subjects included in analysis |
26
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
other [24] | ||||||||||||||||||||||||||||
P-value |
> 0.05 [25] | ||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
Notes [24] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [25] - There was no statistically significant change in any of the haemostatic parameters assessed during the study. |
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End point title |
Functional rating with ALS Functional Rating Scale – Revised (ALSFRS-R) | ||||||||||||||||||||||||||||||||||||
End point description |
Disease severity was evaluated by the Investigator using the ALSFRS-R rating scale in an interview with the patient at Visit 1a (Screening), pre-dose at Visits 2-5 (treatment) and Visits 7-9 (follow-up). ALSFR-S measured 12 different functions (speech, salivation, swallowing, handwriting, cut food and use utensils, dressing and hygiene, turning in bed and adjusting the bedding, walking, climbing stairs, dyspnea, orthopnea and respiratory insufficiency). For each function, 0 to 4 points were assigned, where 0= worst and 4= best. The total ALSFR-S score was the sum of all points collected. The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 2). The parameters were presented as changes from baseline using summary statistics. The overall significance level was 5%. The statistical test used was non-parametric Wilcoxon signed rank sum test, for within patient changes over time.
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End point type |
Secondary
|
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End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
|
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Notes [26] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
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Statistical analysis title |
Increase in total mean ALSFRS-R score | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the full analysis set to assess the statistical significance of changes from baseline.
|
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Comparison groups |
Results at baseline v Results at post-treatment visits
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
26
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
other [27] | ||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 [28] | ||||||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
Notes [27] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [28] - There was a statistically significant increase of total mean ALSFRS-R score during the treatment phase and at the follow-up Visits 7 and 8 (p< 0.05) |
|
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End point title |
Functional rating with Norris scale | ||||||||||||||||||||||||||||||||||||
End point description |
Disease severity was evaluated by the Investigator using the Norris rating scale in an interview with the patient at Visit 1a (Screening), pre-dose at Visits 2-5 (treatment) and Visits 7-9 (follow-up). Norris measured 34 different functions. For each function, 0 to 3 points were assigned, where 0= missing, 1= weak, 2= reduced and 3= normal. The total Norris score was the sum of all points collected. The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 2). The parameters were presented as changes from baseline using summary statistics. The overall significance level was 5%. The statistical test used was non-parametric Wilcoxon signed rank sum test, for within patient changes over time.
|
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End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||
End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
Notes [29] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
|||||||||||||||||||||||||||||||||||||
Statistical analysis title |
Increase in total mean Norris score | ||||||||||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the full analysis set to assess the statistical significance of changes from baseline.
|
||||||||||||||||||||||||||||||||||||
Comparison groups |
Results at baseline v Results at post-treatment visits
|
||||||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
26
|
||||||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||||||
Analysis type |
other [30] | ||||||||||||||||||||||||||||||||||||
P-value |
< 0.05 [31] | ||||||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||||||
Notes [30] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [31] - There was a gradual increase of total mean score during the treatment phase, which was statistically significant at Visits 4, 5 and 6 and during follow-up at Visits 7 and 8 (p< 0.05) . |
|
|||||||||||||||||||||||||||||||||
End point title |
Biomarkers for neurological diseases | ||||||||||||||||||||||||||||||||
End point description |
Extent of presence of biomarkers for neurological diseases was evaluated in serum, plasma and CSF sampled at Visit 1b and Visit 7.
Biomarkers assessed:
In CSF: Albumin, Immunoglobulin G and M (IgG and IgM), IgG index, IgM index, Tau, Phosphorylated Tau, NFL, Beta-amyloid, glial fibrillary acidic protein (GFAP) and Compleasome
In serum: Albumin, IgG and IgM
In plasma: NFL and Compleasome
All biomarkers were presented, using summary statistics, as changes from baseline(Visit 1b) to Visit 7. The overall significance level was 5%. The statistical test used was non-parametric Wilcoxon signed rank sum test, for within patient changes over time.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Visit 1b (screening) and Visit 7 (Day 36, follow-up)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Attachments |
Untitled (Filename: Biomarkers.pdf) |
||||||||||||||||||||||||||||||||
Notes [32] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
|||||||||||||||||||||||||||||||||
Statistical analysis title |
Changes in biomarkers | ||||||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the full analysis set to assess the statistical significance of changes from baseline.
|
||||||||||||||||||||||||||||||||
Comparison groups |
Results at baseline v Results at post-treatment visits
|
||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
26
|
||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||
Analysis type |
other [33] | ||||||||||||||||||||||||||||||||
P-value |
< 0.05 [34] | ||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||
Notes [33] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [34] - There was a decrease in serum IgM (p= 0.006) and an increase in CSF IgM index (p=0.023) from baseline to Follow-up Visit 7. No other statistically significant changes were found in any of the other biomarkers. |
|
|||||||||||||||||||||||||||||
End point title |
Pulmonary function | ||||||||||||||||||||||||||||
End point description |
Pulmonary function was measured as percentage of Forced Vital Capacity (FVC) at Visit 1a (Screening), pre-dose at Visits 2-5 (treatment) and Visits 7-9 (follow-up). The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 2). The overall significance level was 5%. The statistical test used was non-parametric Wilcoxon signed rank sum test, for within patient changes over time.
The mean FVC at baseline (Visit 2) was 84.60% (SD 13.74). Statistically significant changes from this baseline are presented below.
|
||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Attachments |
Untitled (Filename: FVC.docx) |
||||||||||||||||||||||||||||
Notes [35] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
|||||||||||||||||||||||||||||
Statistical analysis title |
Decrease in FVC | ||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the full analysis set to assess the statistical significance of changes from baseline.
|
||||||||||||||||||||||||||||
Comparison groups |
Results at baseline v Results at post-treatment visits
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
26
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
other [36] | ||||||||||||||||||||||||||||
P-value |
< 0.05 [37] | ||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
Notes [36] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [37] - There was a statistically significant decrease in mean FVC at the last dosing day (Visit 6), and at the follow-up Visit 8 and Visit 9. |
|
|||||||||||||||||||||||||||||||||
End point title |
Quality of life | ||||||||||||||||||||||||||||||||
End point description |
The patient’s quality of life (QoL) was evaluated using a visual analogue scale (VAS)-based questionnaire on a scale of 0 to 100, where 0= very bad and 100= very good) which was filled out by the patient and, if applicable, a next of kin. The same next of kin was used throughout the study. The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 2). QoL was reported as changes from baseline using summary statistics.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2, 4 and 6 (days 1, 15 and 29, treatment period) and Visit 8 (days 50, follow-up)
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
Notes [38] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
|||||||||||||||||||||||||||||||||
Statistical analysis title |
No changes in QoL | ||||||||||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the full analysis set to assess the statistical significance of changes from baseline.
|
||||||||||||||||||||||||||||||||
Comparison groups |
Results at baseline v Results at post-treatment visits
|
||||||||||||||||||||||||||||||||
Number of subjects included in analysis |
26
|
||||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||||
Analysis type |
other [39] | ||||||||||||||||||||||||||||||||
P-value |
> 0.05 [40] | ||||||||||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||||
Notes [39] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [40] - No changes in mean QoL score from baseline to the rest of the study. |
|
|||||||||||||||||||||||||
End point title |
Autonomous symptoms | ||||||||||||||||||||||||
End point description |
Prevalence and extent of 16 sensory and autonomous symptoms were recorded by the Investigator in an interview with the patient . The measuring scale was the following: 0= no symptoms, 1= some symptoms, 2= moderate number of symptoms and 3= many symptoms. These parameters were presented as changes from baseline using summary statistics. The overall significance level was 5%. The statistical test used was non-parametric Wilcoxon signed rank sum test, for within patient changes over time.
The total score mean value was 6.2 (SD= 3.5) at baseline (Visit 2) and it was significantly decreased throughout the study (p<0.05). Changes from baseline to Visit 6 (last treatment day) and to Visit 9 (last follow-up) are presented below.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (days 1, 8, 15, 22 and 29, treatment) and Visits 7-9 (days 36, 50 and 99, follow-up)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Notes [41] - This is not a separate analysis set but reports data for the same 13 subjects as at baseline. |
|||||||||||||||||||||||||
Statistical analysis title |
Decrease in total score | ||||||||||||||||||||||||
Statistical analysis description |
The subgroups "Results at baseline" and "Results at post-treatment visits" were only defined in this report in order to describe the statistical analysis. No such analysis sets were used in the study. The statistical analysis was performed within the full analysis set to assess the statistical significance of changes from baseline.
|
||||||||||||||||||||||||
Comparison groups |
Results at baseline v Results at post-treatment visits
|
||||||||||||||||||||||||
Number of subjects included in analysis |
26
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other [42] | ||||||||||||||||||||||||
P-value |
< 0.05 [43] | ||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
Notes [42] - non-parametric Wilcoxon signed rank sum test. This was a within-group comparison in this single-arm study. The number of subjects analyzed shown above as N=26 is incorrect and is due to an innate error of the EudraCT system. The correct number of subjects analyzed for this evaluation is N=13. [43] - The mean score was reduced (relative change) to nearly half at the last dosing day (Visit 6, p= 0.024) and at the end of the study (Visit 9, p= 0.008). |
|
|||||||||||||||||
End point title |
Hepatocyte Growth factor | ||||||||||||||||
End point description |
Blood samples for Hepatocyte Growth Factor (HGF) measurement were collected through venepuncture or through an indwelling venous catheter into a vacutainer tube with citrate. The HGF levels were presented by patient and assessment time as changes from baseline, using summary statistics. The baseline was defined as the last measurement prior to first dose of the test product (i.e. measurement at Visit 2 ,15 min pre-dose).
|
||||||||||||||||
End point type |
Secondary
|
||||||||||||||||
End point timeframe |
Visit 2 (Day 1, treatment) and Visit 6 (day 29, treatment): 15 min pre-dose, 30 min post-dose, 1 hour post-dose, 2 hours post-dose, 2.5 hours post-dose, 3 hours post-dose, 4 hours post-dose and 6 hours post-dose
|
||||||||||||||||
|
|||||||||||||||||
Attachments |
Untitled (Filename: HGF.docx) |
||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Pharmacokinetics of ILB- time to maximum concentration | ||||||||||||
End point description |
Descriptive statistics for time to maximum concentration (tmax) were presented after first and last ILB administration (Visit 2 and Visit 6), as well as pooled data over the dosing days (if appropriate).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Visit 2 (treatment day 1) to Visit 6 (treatment day 29)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Pharmacokinetics of ILB- maximum concentration | ||||||||||||
End point description |
Descriptive statistics for maximum concentration (Cmax) were presented after first and last ILB administration (Visit 2 and Visit 6), as well as pooled data over the dosing days (if appropriate).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Visit 2 (treatment day 1) to Visit 6 (treatment day 29)
|
||||||||||||
|
|||||||||||||
Attachments |
Untitled (Filename: PK graph.docx) |
||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Pharmacokinetics of ILB-terminal elimination | ||||||||||||
End point description |
Descriptive statistics for the terminal elimination (t½ )were presented after first and last ILB administration (Visit 2 and Visit 6), as well as pooled data over the dosing days (if appropriate).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Visit 2 (treatment day 1) to Visit 6 (treatment day 29)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Total study: Visit 1a (Screening), pre-dose at Visits 2-5 (treatment) and Visits 7-9 (follow-up)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
All adverse events (AEs) and SAEs were recorded from start of IMP administration until the end of follow-up (Visit 9). Adverse events that occurred before first IMP treatment were reported separately as baseline events. All AEs presented are treatment-emergent AEs (TEAEs).
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
|
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Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall trial
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||
Substantial protocol amendments (globally) |
|||||||
Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
||||||
18 Dec 2018 |
CSP Section 9.1
Added that a patient can be re-screened, because it was not clearly described in the previous CSP version.
CSP Sections 9.3 and 9.4
Replaced inclusion criterion #6 with exclusion criterion #12, to clarify that only patients with clinically significant abnormal PK-INR, fibrinogen, von Willebrand factor and APTT at screening should be excluded. This change was made because this information was more clearly expressed as an inclusion criterion.
CSP Section 16.7.4
Addition of interim analysis, as an extra review of effects and security.
|
||||||
11 Jul 2019 |
CSP Section 12.3.7
Addition of pregnancy reporting, because it was not included in the previous CSP version, but it is mandatory according to the IHC-GCP.
|
||||||
Interruptions (globally) |
|||||||
Were there any global interruptions to the trial? Yes | |||||||
|
|||||||
Limitations and caveats |
|||||||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
There were 44 protocol deviations reported and they were mainly related to GCP compliance, missing laboratory data and violations of inclusion/exclusion criteria. Other protocol deviations were related to schedule/timing of assessments. |