Clinical Trial Results:
PROSPECTIVE, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED PHASE III STUDY EVALUATING EFFICACY AND SAFETY OF OCTAGAM 10% IN PATIENTS WITH DERMATOMYOSITIS
Summary
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EudraCT number |
2016-002902-37 |
Trial protocol |
CZ DE HU NL RO |
Global end of trial date |
05 Nov 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Nov 2020
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First version publication date |
20 Nov 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 |
GAM10-08
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02728752 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND: 16925 | ||
Sponsors
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Sponsor organisation name |
Octapharma Pharmazeutika Produktionsges.m.b.H.
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Sponsor organisation address |
Oberlaaer Strasse 235, Vienna, Austria, 1100
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Public contact |
Global Clinical Project Manager, Octapharma Pharmazeutika Produktionsges.m.b.H., 0043 1 61032 1168, clinical.department@octapharma.com
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Scientific contact |
Global Clinical Project Manager, Octapharma Pharmazeutika Produktionsges.m.b.H., 0043 1 61032 1168, clinical.department@octapharma.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 |
03 Jul 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Nov 2019
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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 |
To provide confirmatory data on the beneficial effect of 2.0 g/kg of Octagam 10% given every 4 weeks compared with placebo in subjects with active DM based on the percentage of responders at Week 16.
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Protection of trial subjects |
This trial was conducted in accordance to the principles of ICH- GCP, ensuring that the rights, safety and well-being of patients are protected and in consistency with the Declaration of Helsinki and national regulatory requirements. Inclusion and exclusion criteria were carefully defined in order to protect subjects from contraindications, interactions with other medication and risk factors associated with the investigational medicinal product. Study safety was assessed such as monitoring of AEs and SAEs, monitoring of safety lab results, concomitant medication and vital signs.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
27 Feb 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 1
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Country: Number of subjects enrolled |
Poland: 4
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Country: Number of subjects enrolled |
Czech Republic: 12
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Country: Number of subjects enrolled |
Germany: 4
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Country: Number of subjects enrolled |
Hungary: 15
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Romania: 2
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Country: Number of subjects enrolled |
Russian Federation: 21
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Country: Number of subjects enrolled |
Ukraine: 8
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Country: Number of subjects enrolled |
United States: 27
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Worldwide total number of subjects |
95
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EEA total number of subjects |
38
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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) |
75
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From 65 to 84 years |
20
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
Patients with a diagnosis of definite or probable Dermatomyositis according to the Bohan and Peter criteria were were screened according to predefined in- and exclusion criteria. | ||||||||||||||||||||||||
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 |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||
Arm description |
Subjects received 4 infusions of placebo every 4 weeks during the blinded First Period (up to week 16). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects switched to Octagam 10%. After response assessment at Week 16, all subjects with no confirmed deterioration and subjects switched to Octagam 10% due to confirmed deterioration but without further confirmed deterioration during the First Period continued to receive 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who were stable on 2.0 g/kg Octagam 10% could be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to placebo and switched to Octagam 10% due to confirmed deterioration, who deteriorated also during Octagam 10% treatment at 2 consecutive visits were droped-out after response assessment at Week 16 and did not enter the Extension Period. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received 4 infusions of placebo every 4 weeks during the blinded First Period (up to week 16). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects switched to Octagam 10%.
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Arm title
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Octagam 10% | ||||||||||||||||||||||||
Arm description |
Subjects received 4 infusions of 2.0 g/kg Octagam 10% every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects switched to the alternate treatment. After response assessment at Week 16, all subjects with no confirmed deterioration during the First Period continued receiving 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who were stable on 2.0 g/kg Octagam 10% could be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to Octagam and switched to the alternate treatment due to confirmed deterioration were droped-out after response assessment at Week 16 and did not enter the Extension Period. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Octagam 10%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received 4 infusions of 2.0 g/kg Octagam 10% every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects switched to the alternate treatment. After response assessment at Week 16, all subjects with no confirmed deterioration during the First Period continued receiving 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who were stable on 2.0 g/kg Octagam 10% could be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to Octagam and switched to the alternate treatment due to confirmed deterioration were droped-out after response assessment at Week 16 and did not enter the Extension Period.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received 4 infusions of placebo every 4 weeks during the blinded First Period (up to week 16). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects switched to Octagam 10%. After response assessment at Week 16, all subjects with no confirmed deterioration and subjects switched to Octagam 10% due to confirmed deterioration but without further confirmed deterioration during the First Period continued to receive 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who were stable on 2.0 g/kg Octagam 10% could be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to placebo and switched to Octagam 10% due to confirmed deterioration, who deteriorated also during Octagam 10% treatment at 2 consecutive visits were droped-out after response assessment at Week 16 and did not enter the Extension Period. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Octagam 10%
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Reporting group description |
Subjects received 4 infusions of 2.0 g/kg Octagam 10% every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects switched to the alternate treatment. After response assessment at Week 16, all subjects with no confirmed deterioration during the First Period continued receiving 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who were stable on 2.0 g/kg Octagam 10% could be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to Octagam and switched to the alternate treatment due to confirmed deterioration were droped-out after response assessment at Week 16 and did not enter the Extension Period. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received 4 infusions of placebo every 4 weeks during the blinded First Period (up to week 16). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects switched to Octagam 10%. After response assessment at Week 16, all subjects with no confirmed deterioration and subjects switched to Octagam 10% due to confirmed deterioration but without further confirmed deterioration during the First Period continued to receive 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who were stable on 2.0 g/kg Octagam 10% could be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to placebo and switched to Octagam 10% due to confirmed deterioration, who deteriorated also during Octagam 10% treatment at 2 consecutive visits were droped-out after response assessment at Week 16 and did not enter the Extension Period. | ||
Reporting group title |
Octagam 10%
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Reporting group description |
Subjects received 4 infusions of 2.0 g/kg Octagam 10% every 4 weeks during the blinded First Period (16 weeks). If confirmed deterioration (deterioration at 2 consecutive visits) during the First Period, subjects switched to the alternate treatment. After response assessment at Week 16, all subjects with no confirmed deterioration during the First Period continued receiving 2.0 g/kg of Octagam 10% every 4 weeks during the subsequent 6-months open-label Extension Period. At Week 28, subjects who were stable on 2.0 g/kg Octagam 10% could be switched to 1.0 g/kg Octagam 10%, at the discretion of the investigator. Subjects randomized to Octagam and switched to the alternate treatment due to confirmed deterioration were droped-out after response assessment at Week 16 and did not enter the Extension Period. | ||
Subject analysis set title |
Full Analysis Set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
The full analysis set (FAS) is defined according to the intention-to-treat principle and consists of all
randomized subjects. It is expected that the FAS will coincide with the safety set.
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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 (SAF) consists of all subjects who received at least part of one infusion of Octagam or placebo.
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Subject analysis set title |
Time to Minimal Improvement Placebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Time to Minimal Improvement - From Start of First Treatment in Overall Period
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Subject analysis set title |
Time to Minimal Improvement Octagam 10%
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Time to Minimal Improvement - From Start of First Treatment in Overall Period
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Subject analysis set title |
Time to Moderate Improvement Placebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Time to Moderate Improvement - From Start of First Treatment in Overall Period
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Subject analysis set title |
Time to Moderate Improvement Octagam 10%
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Time to Moderate Improvement - From Start of First Treatment in Overall Period
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Subject analysis set title |
Time to Major Improvement Placebo
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Time to Major Improvement - From Start of First Treatment in Overall Period
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Subject analysis set title |
Time to Major Improvement Octagam 10%
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Time to Major Improvement - From Start of First Treatment in Overall Period
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End point title |
Number of Patients Who Had an Increase of ≥20 Points on the Total Improvement Score (TIS) | ||||||||||||||||||
End point description |
Proportion of responders in the 2.0 g/kg Octagam 10% and placebo arms at Week 16 relative to baseline (Week 0). A responder being defined as a patient with an increase of ≥20 points on the Total Improvement Score (TIS, a scale from 0 to 100; 20-39 points being minimal improvement, 40-59 points being moderate improvement, and ≥60 points being major improvement
Full Analysis Set : Octagam (N=47) Placebo (N=48)
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End point type |
Primary
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End point timeframe |
At week 16
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Statistical analysis title |
Proportion of Responders | ||||||||||||||||||
Statistical analysis description |
The primary endpoint measure ‘response’ was assessed at Week 16 based on the TIS score. The proportion of responders within both treatment groups was compared by the Cochran-Mantel-Haenszel test, stratified by GDA at baseline (randomization stratum), using a two-sided alpha level of 0.05. The primary analysis was to be considered a
success if the proportion of responders was significantly higher in the octagam 10% group compared to the placebo group.
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Comparison groups |
Placebo v Octagam 10%
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Number of subjects included in analysis |
95
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0008 | ||||||||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||||||||
Parameter type |
Difference in Response Rate | ||||||||||||||||||
Point estimate |
34.97
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
16.7 | ||||||||||||||||||
upper limit |
53.24 |
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End point title |
Proportion of TIS Responders by Improvement Category at Week 16 | ||||||||||||||||||||||||||||||
End point description |
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
Full Analysis Set : Octagam (N=47) Placebo (N=48)
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End point type |
Secondary
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End point timeframe |
16 weeks
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No statistical analyses for this end point |
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End point title |
Proportion of TIS Responders by Improvement Category at Week 40 | ||||||||||||||||||||||||||||||
End point description |
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
Forty-five patients in the octagam 10% group and 46 patients in the placebo group completed the First Period and entered the 24-week Extension Period during which all patients received open-label octagam 10% treatment.
Full Analysis Set : Octagam (N=47) Placebo (N=48)
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End point type |
Secondary
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End point timeframe |
40 weeks
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) | ||||||||||||||||||
End point description |
The modified CDASI has 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron’s papules on the hands are evaluated both for activity and damage. Lastly, the activity of periungual changes and alopecia is assessed.
Full Analysis Set : Octagam (N=47) Placebo (N=48)
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End point type |
Secondary
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End point timeframe |
First 16 weeks
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No statistical analyses for this end point |
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End point title |
Mean Change From End of First Period (Week 16) to End of Extension Period (Week 40) in the Modified Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) | ||||||||||||||||||
End point description |
The modified CDASI has 3 activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures (poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron’s papules on the hands are evaluated both for activity and damage. Lastly, the activity of periungual changes and alopecia is assessed.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
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End point type |
Secondary
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End point timeframe |
From week 16 to Week 40
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in: SF-36v2 Health Survey | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.
Different numbers of patients analyzed in each group due to patient discontinuation.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
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End point type |
Secondary
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End point timeframe |
From start of the trial till Week 16
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in: SF-36v2 Health Survey | ||||||||||||||||||||||||||||||||||||||||||
End point description |
The SF-36 is a multi-purpose, short-form health survey with only 36 questions. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
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End point type |
Secondary
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End point timeframe |
From start of the trial till Week 40
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in Physician’s Global Disease Activity | ||||||||||||
End point description |
10 cm VAS assessing global disease activity from “No evidence of disease activity” to “Extremely active or severe disease activity”; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). Assessment completed by physician. 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
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End point type |
Secondary
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End point timeframe |
From start of the trial till Week 16
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in Physician’s Global Disease Activity | ||||||||||||
End point description |
10 cm VAS assessing global disease activity from “No evidence of disease activity” to “Extremely active or severe disease activity”; Disease Activity being defined as potentially reversible pathology or physiology resulting from the myositis). Assessment completed by physician. 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
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End point type |
Secondary
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End point timeframe |
From start of the trial till Week 40
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in: Patient Global Disease Activity | ||||||||||||
End point description |
Patient’s Global Disease Activity (10cm VAS assessing the overall activity of the patient’s disease today from “No evidence of disease activity” to “Extremely active or severe disease activity”, Disease Activity being active inflammation in the patient’s muscles, skin, joints, intestines, heart, lungs or other parts of the body, which can improve when treated with medicines). 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
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End point type |
Secondary
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End point timeframe |
From start of the trial till Week 16
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in: Patient Global Disease Activity | ||||||||||||
End point description |
Patient’s Global Disease Activity (10cm VAS assessing the overall activity of the patient’s disease today from “No evidence of disease activity” to “Extremely active or severe disease activity”, Disease Activity being active inflammation in the patient’s muscles, skin, joints, intestines, heart, lungs or other parts of the body, which can improve when treated with medicines). 0 is lowest score and 10 is highest score. Higher score associated with worse outcome.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
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End point type |
Secondary
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End point timeframe |
From start of the trial till Week 40.
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No statistical analyses for this end point |
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End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in: MMT-8 | ||||||||||||
End point description |
Manual Muscle Testing - MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 – 150]. Higher score associated with better outcome.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
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End point type |
Secondary
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End point timeframe |
From start of the trial till Week 16
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|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Measure Title Mean Change From Baseline (Week 0) to Extension Period (Week 40) in: MMT-8 | ||||||||||||
End point description |
Manual Muscle Testing - MMT-8; a set of 8 designated muscles tested bilaterally [potential score 0 – 150]. Higher score associated with better outcome.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Time Frame From start of the trial till Week 40
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in: Health Assessment Questionnaire | ||||||||||||
End point description |
Health Assessment Questionnaire (HAQ); a generic rather than a disease-specific instrument; comprised of 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 [without any difficulty] to 3 [unable to do]. For each section the score given to that section is the worst score within the section. The 8 scores of the 8 sections are summed and divided by 8). Assessment completed by patients. Lowest score 0 highest score 24. Higher score associated with worse outcome.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 16
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in: Health Assessment Questionnaire | ||||||||||||
End point description |
Health Assessment Questionnaire (HAQ); a generic rather than a disease-specific instrument; comprised of 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 [without any difficulty] to 3 [unable to do]. For each section the score given to that section is the worst score within the section. The 8 scores of the 8 sections are summed and divided by 8). Assessment completed by patients. Lowest score 0 highest score 24. Higher score associated with worse outcome.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 40
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in Enzymes (Alanine Aminotransferase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 16
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in Enzymes (Alanine Aminotransferase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 40
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in Enzymes (Aspartate Aminotransferase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 40
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in Enzymes (Aspartate Aminotransferase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 40
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in Enzymes (Lactate Dehydrogenase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 16
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in Enzymes (Lactate Dehydrogenase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 40.
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in Enzymes (Aldolase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 16
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in Enzymes (Aldolase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 40
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in Enzymes (Creatine Kinase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 16
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in Enzymes (Creatine Kinase) | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial till Week 40
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to End of First Period (Week 16) in: Extra-muscular Activity | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial until Week 16
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean Change From Baseline (Week 0) to Extension Period (Week 40) in: Extra-muscular Activity | ||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From start of the trial until Week 40
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean TIS From Baseline (Week 0) to End of First Period (Week 16) | ||||||||||||
End point description |
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 16 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Mean TIS From Baseline (Week 0) to End of Extension Period (Week 40) | ||||||||||||
End point description |
The TIS (Total Improvement Score) is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM: ≥20 to 39 points being minimal improvement, ≥40 to 59 points being moderate improvement, and ≥60 points being major improvement.
Full Analysis Set : Octagam (N=47) Placebo (N=48) Different numbers of patients analyzed in each group due to patient discontinuation.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 40 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to Minimal Improvement in TIS | ||||||||||||
End point description |
When interpreting these time to event evaluations, one has to keep in mind that eventually all patients were treated with octagam 10%, so that differences in time to response for the Overall Period reflect this delayed start of treatment rather than the true difference between treatment with octagam 10% and placebo.
Full Analysis Set: Octagam (N=47) Placebo (N=48)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 40 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to Moderate Improvement in TIS | ||||||||||||
End point description |
When interpreting these time to event evaluations, one has to keep in mind that eventually all patients were treated with octagam 10%, so that differences in time to response for the Overall Period reflect this delayed start of treatment rather than the true difference between treatment with octagam 10% and placebo.
Full Analysis Set: Octagam (N=47) Placebo (N=48)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
up to 40 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Time to Confirmed Deterioration in the First Period | ||||||||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48)
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to week 16
|
||||||||||||||||||
|
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
Time to Confirmed Deterioration Overall | ||||||||||||||||||
End point description |
Full Analysis Set : Octagam (N=47) Placebo (N=48)
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Up to 40 weeks
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [1] - No result due to limited sample size [2] - No result due to limited sample size |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Time to Major Improvement in TIS | ||||||||||||
End point description |
When interpreting these time to event evaluations, one has to keep in mind that eventually all patients were treated with octagam 10%, so that differences in time to response for the Overall Period reflect this delayed start of treatment rather than the true difference between treatment with octagam 10% and placebo.
Full Analysis Set: Octagam (N=47) Placebo (N=48)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Up to 40 weeks
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
40 weeks
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.0
|
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Reporting groups
|
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Reporting group title |
First Period Placebo
|
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Period Octagam
|
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
07 Jul 2017 |
Amendment 3:
-Following a recommendation of the Steering Committee inclusion of patients with Dermatomyositis who are under no current treatment due to intolerance and/or non-responsiveness to DM-related medication has been added
-upon recommendation by the Steering Committee exclusion criterion was amended to shorten the waiting period for patients after excision of basal or squamous cell skin cancer
-Following a recommendation by the Steering Committee Subjects diagnosed with Juvenile Dermatomyositis were excluded from the study.
- further specification of some exclusion criteria
-Maximally allowed stable dose as concomitant therapy for Hydroxychloroquine was re-defined
-in accoedance with the Steering Committee the definition of “Confirmed deterioration” was updated
-As requested by the study’s Independent Adjudication Committee Thyroid-stimulating hormone (TSH) was added to the clinical chemistry test panel
- Details on breaking the blind have been udated upon request of the Czech Regulatory Authority |
||
18 Jul 2018 |
Amendment 4:
-The maximum infusion rate has been reduced to 0.04 mL/kg/min upon request of FDA
-Duration of infusion cycles for extension period changed from 2 days to 2-5 days
-Upon FDA request a new stopping rule was implemented for TEEs observed on or after the cut-off date of 04-Jul-2018 (since introduction of reduced maximum infusion rate of 0.04 mL/kg/min)
-Thromboembolic events will be reported as SAE (medical occurrence that at any dose is another important medical event)
- Exclusion criterion with reference to forbidden medication has been added for clarification
-Time window defined for Direct Coombs’ test taken prior infusion cycle has been extended for administrative reason |
||
05 Nov 2018 |
Amendment 6:
-Exclusion criterion was extended so that patients with any prior TEE event, regardless of the onset of the event, are not be eligible for participation in the study
-References were added to explicitly state the higher risk for thromboembolic events in “newly” diagnosed patients with DM.
-For the safety of patients with risk factors for thromboembolic events or patients who are in the initial disease stage after diagnosis the Permitted Concomitant Therapy Section has been amended wit the information that TEE prophylaxis, if deemed necessary by the investigator, is allowed as a precautionary measure and should follow standard of care. Its use must be documented. |
||
12 Mar 2019 |
Amendment 7:
Early Termination section has been updated based on the opinion of the IDMC. TEEs with a likely temporal and cause-effect relationship which occur in a single subject within a short clinical time period should be counted as a single adverse events of special interest (AESI) including for the calculations performed for stopping rules. |
||
03 Jul 2019 |
Amendment 8:
-As requested by FDA the definition of responders in study protocol was reworded and the primary endpoint was reworded subsequently in order to be unambiguous
|
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |