Clinical Trial Results:
A Multicenter, Prospective, Open-Label, Non-Controlled Clinical Trial to Assess the Efficacy and Safety of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) in Patients With Myasthenia Gravis Exacerbations
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Summary
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EudraCT number |
2013-005098-28 |
Trial protocol |
CZ HU BE RO PL EE LV |
Global end of trial date |
17 Apr 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Apr 2019
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First version publication date |
03 Apr 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
GTI1305
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02413580 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Grifols Therapeutics LLC
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Sponsor organisation address |
79 TW Alexander Drive, Research Triangle Park, North Carolina, United States, NC 27709
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Public contact |
Rhonda Griffin, Grifols Therapeutics LLC, rhonda.griffin@grifols.com
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Scientific contact |
Rhonda Griffin, Grifols Therapeutics LLC, rhonda.griffin@grifols.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Apr 2018
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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 |
17 Apr 2018
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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 evaluate the efficacy of an intravenous (IV) infusion of Immune Globulin (Human), 10% Caprylate/Chromatography Purified (IGIV-C) (total dose of 2 grams per kilogram [g/kg] administered over 2 consecutive days at a dose of 1 g/kg per day) in subjects with myasthenia gravis (MG) exacerbations (not attributable to an infection or change in medication) by assessing the change in score of MG symptoms as measured by the Quantitative Myasthenia Gravis (QMG) scale from Baseline to Day 14.
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Protection of trial subjects |
Standards for Good Clinical Practice were adhered to for all procedures in this clinical study. The investigators ensured that the clinical study was conducted in full conformance with appropriate local laws and regulations and the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jun 2015
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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 |
Argentina: 3
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Country: Number of subjects enrolled |
Canada: 3
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Country: Number of subjects enrolled |
Russian Federation: 10
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Country: Number of subjects enrolled |
South Africa: 2
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Country: Number of subjects enrolled |
Poland: 4
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Country: Number of subjects enrolled |
Romania: 5
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Country: Number of subjects enrolled |
Belgium: 6
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Country: Number of subjects enrolled |
Czech Republic: 4
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Latvia: 10
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Worldwide total number of subjects |
49
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EEA total number of subjects |
31
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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) |
42
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Forty-nine subjects with MG exacerbations falling in the class IVb-V of the disease severity staging proposed by the Myasthenia Gravis Foundation of America (MGFA) were enrolled. MG exacerbations were characterized by worsening muscle weakness causing swallowing difficulty, acute respiratory failure or major functional disability. | ||||||||||||||
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Pre-assignment
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Screening details |
There was no separate screening visit; screening evaluations were performed at the Baseline Visit (Day 0). | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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All subjects | ||||||||||||||
Arm description |
Subjects with MG exacerbations not attributable to an infection or change in medication were planned to receive 2 g/kg of IGIV-C on Day 0 (Baseline) and on Day 1 (dosed as 1 g/kg per day), followed by 28 days of post-infusion assessments. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Gamunex-C
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Investigational medicinal product code |
IGIV-C
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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 |
1 g/kg of IGIV-C was administered as IV infusions over 2 consecutive days so that subjects received a total dose of 2 g/kg.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
Subjects with MG exacerbations not attributable to an infection or change in medication were planned to receive 2 g/kg of IGIV-C on Day 0 (Baseline) and on Day 1 (dosed as 1 g/kg per day), followed by 28 days of post-infusion assessments. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
All subjects
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Reporting group description |
Subjects with MG exacerbations not attributable to an infection or change in medication were planned to receive 2 g/kg of IGIV-C on Day 0 (Baseline) and on Day 1 (dosed as 1 g/kg per day), followed by 28 days of post-infusion assessments. | ||
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End point title |
Mean Change in QMG Scale Score from Baseline (Day 0) to Day 14 [1] | ||||||||
End point description |
The mean change in the QMG score from Baseline to Day 14 in the Evaluable population is presented. The QMG scale consists of 13 test items, each of which was given a score of either 0 (no symptoms), 1 (mild symptoms), 2 (moderate symptoms) or 3 (severe symptoms). The Evaluable population was defined as all subjects who received the entire dose of investigational product (IP) (2 g/kg over 2 consecutive days) and had valid Baseline and Day 14 QMG score measurements. The change in QMG score from Baseline to Day 14 was analyzed using the paired t-test (p<0.001, 95% confidence interval [CI]: -7.957 to -4.787).
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End point type |
Primary
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End point timeframe |
From Baseline (Day 0) to Day 14.
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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: As data is presented for a single reporting arm, the analysis of the change from Baseline to Day 14 is reported within the end point description. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Clinical Improvement as Assessed by at Least a 3-Point Decrease in the QMG Scale from Baseline (Day 0) to Day 14 | ||||||||
End point description |
The percentage of subjects with clinical improvement at Day 14 as assessed by the QMG scale in the Evaluable population is presented. The QMG scale consists of 13 test items, each of which was given a score of either 0 (no symptoms), 1 (mild symptoms), 2 (moderate symptoms) or 3 (severe symptoms). Subjects with clinical improvement had at least a 3-point decrease from Baseline in QMG score. The Evaluable population was defined as all subjects who received the entire dose of IP (2 g/kg over 2 consecutive days) and had valid Baseline and Day 14 QMG score measurements.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) to Day 14.
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Clinical Improvement as Assessed by at Least a 2-Point Decrease in the MG-Activities of Daily Living (MG-ADL) from Baseline (Day 0) to Day 14 | ||||||||
End point description |
The percentage of subjects with clinical improvement at Day 14 as assessed by the MG-ADL in the Evaluable population is presented. The MG-ADL is an 8-item, patient-reported questionnaire that is completed to assess the symptoms and activities of MG. Each item is scored from 0 (normal/no symptoms) to 3 (severe symptoms). Clinical improvement was defined as at least a 2-point decrease in the MG-ADL score. The Evaluable population was defined as all subjects who received the entire dose of IP (2 g/kg over 2 consecutive days) and had valid Baseline and Day 14 QMG score measurements.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 0) to Day 14.
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Clinical Improvement as Assessed by at Least a 3-Point Decrease in the MG Composite Scale from Baseline (Day 0) to Day 14 | ||||||||
End point description |
The percentage of subjects with clinical improvement at Day 14 as assessed by the MG Composite scale in the Evaluable population is presented. The MG Composite scale is a quantitative measure for determining improvement and worsening for subjects with generalized MG. It consists of 3 ocular, 3 bulbar, 1 respiratory, 1 neck and 2 limb items. The total score ranges from 0 to 50, with a higher score indicating more severe symptoms. Clinical improvement was defined as at least a 3-point decrease in the MG-ADL score. The Evaluable population was defined as all subjects who received the entire dose of IP (2 g/kg over 2 consecutive days) and had valid Baseline and Day 14 QMG score measurements.
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End point type |
Secondary
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End point timeframe |
From Baseline (Day 0) to Day 14.
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From Baseline (Day 0) up to Day 28.
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Adverse event reporting additional description |
Adverse events are reported for the Safety population which consisted of all subjects who received any amount of IP.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
All subjects
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Reporting group description |
Subjects with MG exacerbations not attributable to an infection or change in medication were planned to receive 2 g/kg of IGIV-C on Day 0 (Baseline) and on Day 1 (dosed as 1 g/kg per day), followed by 28 days of post-infusion assessments. | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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19 Jun 2014 |
-The percentage of subjects with clinical improvement was included and was defined by 3-point decreases in QMG and MG Composite scores and by 2-point decreases in MG-ADL scores.
-MGFA post-intervention status was removed from Days 7, 21 and 28.
-The time frame for long-term corticosteroid (CS) treatment for MG was 8 weeks.
-Inclusion and exclusion criteria were updated with respect to use of contraception to prevent pregnancy during the course of the clinical study.
-CS treatment newly initiated within 8 weeks and any IPs received within 3 months prior to study participation were prohibited.
-Instructions for restricted concomitant medications during the clinical study were updated to prohibit cholinesterase inhibitors within 12 hours prior to assessment, and within 24 hours prior to assessment for subjects receiving slow-release cholinesterase inhibitors.
-Thromboembolic events and hemolysis were added as AEs of special interest, and assessments were added on Days 1, 7 and 21 for additional safety monitoring. |
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03 Sep 2015 |
- Biomarker testing for peripheral blood mononucleated cells was removed from the clinical study.
- The central laboratory could have been used if the local laboratory was unable to perform hemolysis laboratory testing.
- Blood testing included serum or plasma free hemoglobin.
- Instructions were provided that MG assessments should be performed by the same clinical staff member, if possible.
- The definition of ‘infection’ was updated to be defined as ‘evident infection’ which included, but was not limited to, the presence of at least one of the following diagnostic features: axillary temperature ≥38°C, positive blood culture of infective microorganism, white blood cell (WBC) count >12×10^9/L and differential WBC count of >10% band neutrophils (>1.2×10^9/L), and pulmonary infiltrate with consolidation on chest X-ray. Alternatively, other signs and symptoms could have been considered for the diagnosis of evident infection according to the investigator’s judgement.
- Use of prophylactic anti-coagulant therapy would not be considered ‘exceptional’ when administered during hospitalization as prophylactic treatment as part of standard of care for deep vein thrombosis prevention.
- Prohibited medications were updated to include systemic antibiotic therapy.
- Physical examinations did not include breast and genitourinary areas.
- The Baseline Visit was to occur after the subject was stabilized according to the investigator’s judgement. |
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30 Mar 2016 |
- There was no screening visit in this clinical study.
- Subjects with hemoglobin levels <9 grams/deciliter were not eligible for clinical study participation. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| As subjects may have been intubated or otherwise compromised, and the assessments may have been performed in extenuating circumstances, it was necessary to standardize methodology to obtain consistent scoring across study centers. | |||
