Clinical Trial Results:
Phase II Trial of low-dose Sandimmun Optoral ® (Cyclosporine A) for the treatment of primary Sjögren's syndrome (pSS)
Summary
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EudraCT number |
2009-013976-38 |
Trial protocol |
DE |
Global end of trial date |
11 Feb 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
28 May 2022
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First version publication date |
28 May 2022
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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 |
COLO400BDE02T
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01693393 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Charité - University Hospital of Berlin
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Sponsor organisation address |
Charitéplatz 1, Berlin, Germany, 10117
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Public contact |
Dr. Jan Zernicke, Medizinische Klinik m.S. Rheumatologie und Klinische Immunologie - Forschung, +49 030450 513025, jan.zernicke@charite.de
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Scientific contact |
Dr. Jan Zernicke, Medizinische Klinik m.S. Rheumatologie und Klinische Immunologie - Forschung, +49 030450 513025, jan.zernicke@charite.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 |
11 Feb 2015
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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 |
11 Feb 2015
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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 |
Evaluation of efficacy of low-dose Cyclosporine A in patients with primary Sjögren’s Syndrome and joint involvement after 16 week treatment period.
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Protection of trial subjects |
The study was reviewed and approved by the Independent
Ethics Committee of Berlin (Landesamt für Gesundheit und
Soziales (LaGeSo)) and conducted according to the ethical
principles of the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Dec 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: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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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) |
30
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
patients were recruited during a period of symptoms, the observed improvement could also be influenced by the variation of intensity of symptoms | ||||||||||||
Pre-assignment
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Screening details |
Key inclusion criteria: a minimum of three tender joints and/or three swollen joints at screening and baseline, normal hematological, renal and liver lab results, stable treatment of Sjögren’s syndrome meaning stable doses of nonsteroidal anti-inflammatory drug and glucocorticoid. 36 Patients screened 6 screening failures 30 Patients randomized | ||||||||||||
Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Arms
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Arm title
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Cyclosporine A | ||||||||||||
Arm description |
- | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Sandimmun Optoral
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Treatment consisted of the intake of low-dose CyA (approximately 2 mg kg−1 body weight day−1 divided in two intakes) over a period of 16 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Cyclosporine A
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Cyclosporine A
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Reporting group description |
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Subject analysis set title |
Baseline
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All statistical analyses were performed in the intention to treat (ITT) collective. Twenty-eight (including six patients who dropped out during the study) had an EOT visit. For the two patients who were lost to follow-up (LTFU) after the baseline visit, the last observation carried forward (LOCF) method was used to impute the missing data.
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End point title |
Change of the joints (tender/swollen) | ||||||||||||||||||||||||
End point description |
Comparison between Baselin (BL) and end of treatment (EOT);
TJC tender joint count, SJC swollen joint count,
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End point type |
Primary
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End point timeframe |
16 Weeks
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Attachments |
Joint count |
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Statistical analysis title |
improvement of number of swollen and tender joint | ||||||||||||||||||||||||
Statistical analysis description |
All statistical analyses were performed in the intention to treat (ITT) collective. Twenty-eight (including six patients who dropped out during the study) had an EOT visit. For the two patients who were lost to follow-up (LTFU) after the baseline visit, the last observation carried forward (LOCF) method was used to impute the missing data. Figure 1 summarizes the flow of patients.
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Comparison groups |
Cyclosporine A v Baseline
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Number of subjects included in analysis |
60
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||||||||||
P-value |
≤ 0.05 | ||||||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||||||
Confidence interval |
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End point title |
Changes of the safety profile in patients | ||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
DAS28 disease activity score using the 28 joint count, CRP C-reactive Protein, ESR erythrocyte sedimentation rate, ESSDAI EULAR Sjögren’s Syndrome Disease Activity Index, SF36 Short Form with 36 questions, MHD mental health domain, PHD physical health domain, HAQ-DI health assessment questionnaire disability index.
For more detailed Secondary Endpoints see attachment
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End point type |
Secondary
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End point timeframe |
16 weeks
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Attachments |
Changes from BL to EOT DAS28 |
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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 |
16 weeks
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Adverse event reporting additional description |
No new or unexpected safety observations were made. Among the 30 patients, all had experienced at least one adverse event (AE). Gastrointestinal disorders were the most common AEs. All AEs were mild or moderate with exception of one serious AE (hypertension).
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.1
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Reporting groups
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Reporting group title |
Cyclosporine A
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Reporting group description |
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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 | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/27470087 |