Clinical Trial Results:
Mycophenolate sodium in Graves’ orbitopathy
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Summary
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EudraCT number |
2008-002123-93 |
Trial protocol |
DE |
Global end of trial date |
10 May 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jan 2020
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First version publication date |
26 Jan 2020
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Other versions |
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Summary report(s) |
Lancet Diabetes Endocrinol 2018 |
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 |
MINGO
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University Medical Center Mainz
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Sponsor organisation address |
Langenbeckstreet 1, Mainz, Germany,
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Public contact |
Professor George J. Kahaly, University Medical Center Mainz, george.kahaly@unimedizin-mainz.de
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Scientific contact |
Professor George J. Kahaly, University Medical Center Mainz, george.kahaly@unimedizin-mainz.de
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Sponsor organisation name |
University Medical Center Mainz
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Sponsor organisation address |
Langenbeckstreet 1, Mainz, Germany,
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Public contact |
George J. Kahaly
University Medical Center Mainz
Langenbeckstreet 1
55131 Mainz, George J. Kahaly
University Medical Center Mainz
Langenbeckstreet 1
55131 Mainz, george.kahaly@unimedizin-mainz.de
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Scientific contact |
George J. Kahaly
University Medical Center Mainz
Langenbeckstreet 1
55131 Mainz, George J. Kahaly
University Medical Center Mainz
Langenbeckstreet 1
55131 Mainz, george.kahaly@unimedizin-mainz.de
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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 |
07 Jun 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
10 May 2017
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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 |
- Response rate at week 12: comparison of the combination treatment vs. steroid monotherapy
- Relapse rate at weeks 24 and 36 in both groups
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Protection of trial subjects |
All patients underwent complete ophthalmic and endocrine assessment at baseline and 6, 12, 24, and 36 weeks after starting treatment. Secondary Endpoint was safety of the combination treatment Mycophenolate Sodium + Methylprednisolone i.v. Adverse events were documented and coded in accordance with the standardised medical dictionary for regulatory affairs (MedDRA),17–19 as recommended by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Nov 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 137
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Country: Number of subjects enrolled |
Italy: 27
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Worldwide total number of subjects |
164
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EEA total number of subjects |
164
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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) |
153
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||
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Pre-assignment
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Screening details |
Baseline assessments (general medical history, laboratory tests, endocrine and ophthalmic investigations, physical examination, vital signs, subjective assessments) may also be performed up to 2 weeks before baseline (Screening period). Results must be available and negative prior to administration of medication. | |||||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind [1] | |||||||||
Roles blinded |
Data analyst, Investigator [2] | |||||||||
Blinding implementation details |
All ophthalmologists and the Johannes Gutenberg University expert statistician were masked to group assignment.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Methylprednisolone Monotherapy | |||||||||
Arm description |
During the first 12 weeks, intravenous methylprednisolone was administered to all patients at 500 mg once per week for 6 weeks, then 250 mg once per week for 6 weeks with a cumulative dose of 4·5 g. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Methylprednisolone
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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 |
During the first 12 weeks, intravenous methylprednisolone was administered to all patients at 500 mg once per week for 6 weeks, then 250 mg once per week for 6 weeks with a cumulative dose of 4·5 g.
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Arm title
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Methylprednisolone and Mycophenolate Sodium | |||||||||
Arm description |
During the first 12 weeks, intravenous methylprednisolone was administered to all patients at 500 mg once per week for 6 weeks, then 250 mg once per week for 6 weeks with a cumulative dose of 4·5 g. In addition to the methylprednisolone, patients in the combination methylprednisolone and mycophenolate group also received 360 mg of mycophenolate orally twice per day for 24 weeks with a cumulative mycophenolate dose of 120 g. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Mycophenolate Sodium
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
During the first 12 weeks, intravenous methylprednisolone was administered to all patients at 500 mg once per week for 6 weeks, then 250 mg once per week
for 6 weeks with a cumulative dose of 4·5 g. In addition to the methylprednisolone, patients in the combination methylprednisolone and mycophenolate group also received 360 mg of mycophenolate orally twice per day for 24 weeks with a cumulative mycophenolate dose of 120 g.
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| Notes [1] - The number of roles blinded appears inconsistent with a single blinded trial. It is expected that there will be one role blinded in a single blind trial. Justification: The trial was observer-masked. Only Opththalmologists and the statistician were blinded to treatment allocation. [2] - The roles blinded appear inconsistent with a simple blinded trial. Justification: The trial was observer-masked. Only Opththalmologists and the statistician were blinded to treatment allocation. |
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End points reporting groups
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Reporting group title |
Methylprednisolone Monotherapy
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Reporting group description |
During the first 12 weeks, intravenous methylprednisolone was administered to all patients at 500 mg once per week for 6 weeks, then 250 mg once per week for 6 weeks with a cumulative dose of 4·5 g. | ||
Reporting group title |
Methylprednisolone and Mycophenolate Sodium
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Reporting group description |
During the first 12 weeks, intravenous methylprednisolone was administered to all patients at 500 mg once per week for 6 weeks, then 250 mg once per week for 6 weeks with a cumulative dose of 4·5 g. In addition to the methylprednisolone, patients in the combination methylprednisolone and mycophenolate group also received 360 mg of mycophenolate orally twice per day for 24 weeks with a cumulative mycophenolate dose of 120 g. | ||
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End point title |
Response rate at week 12: comparison of the combination treatment vs. steroid | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Baseline to week 12
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Statistical analysis title |
Primary outcome | |||||||||
Comparison groups |
Methylprednisolone Monotherapy v Methylprednisolone and Mycophenolate Sodium
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Number of subjects included in analysis |
149
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Fisher exact | |||||||||
Confidence interval |
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| Notes [1] - Comparison |
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Adverse events information [1]
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Timeframe for reporting adverse events |
From Baseline to visit 36 weeks
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
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Reporting groups
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Reporting group title |
Safety Analysis
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Reporting group description |
from baseline to visit 36 weeks | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Frequency threshold for reporting non-serious adverse Events was set at 5%. No AE occurred in more than 3 patients; a detailed safety analysis is given in the attached manuscript. |
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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? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
