Clinical Trial Results:
A pilot study towards a therapy with prednisolone encapsulated liposomes for the treatment of Graves’ Orbitopathy with reduced systemic steroid exposure
Summary
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EudraCT number |
2017-001158-33 |
Trial protocol |
NL |
Global end of trial date |
19 Dec 2019
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Results information
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Results version number |
v2(current) |
This version publication date |
28 Jan 2021
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First version publication date |
07 Mar 2020
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Other versions |
v1 |
Version creation reason |
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Summary report(s) |
Abstract (PMID 33423386) |
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 |
OZR-2016-34
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Nederlands Trial Register: NL6404 | ||
Sponsors
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Sponsor organisation name |
The Rotterdam Eye Hospital
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Sponsor organisation address |
PO Box 70030, Rotterdam, Netherlands, 3000LM
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Public contact |
Rotterdam Ophthalmic Institute, The Rotterdam Eye Hospital, 31 104023430, r.wubbels@oogziekenhuis.nl
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Scientific contact |
Rotterdam Ophthalmic Institute, The Rotterdam Eye Hospital, 31 104023430, r.wubbels@oogziekenhuis.nl
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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 |
28 Jan 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Dec 2019
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Dec 2019
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To demonstrate that Nanocort is safe and effectively reduces the inflammatory signs and symptoms of active GO.
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Protection of trial subjects |
In this study it is hypothesized that treatment of Graves' Orbitopathy with lower doses of long-circulating liposomal prednisolone (Nanocort, LCLP), instead of high doses of methylprednisolone, can be effective while the number of adverse events is reduced.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Nov 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: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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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) |
8
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From 65 to 84 years |
2
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85 years and over |
0
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Recruitment
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Recruitment details |
Rotterdam Eye Hospital, Netherlands, november 2017 until december 2018. | ||||||||||||
Pre-assignment
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Screening details |
Moderate-to-severe Graves' orbitopathy, clinical activity score (CAS) ≥ 3. | ||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
Arms
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Arm title
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Nanocort | ||||||||||||
Arm description |
All participants received treatment. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Pegylated Liposomal Prednisolone Sodium Phosphate (Nanocort)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Dispersion for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects will be treated with 150 mg/infusion of Nanocort administered as an IV infusion at week 1 and 3.
Nanocort will be infused over approximately 2.5 hours.
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Baseline characteristics reporting groups
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Reporting group title |
Nanocort
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Reporting group description |
All participants received treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
CAS
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Clinical activity score
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End points reporting groups
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Reporting group title |
Nanocort
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Reporting group description |
All participants received treatment. | ||
Subject analysis set title |
CAS
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Clinical activity score
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End point title |
Sustained response [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
Sustained response at 6 and 13 weeks.
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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: Due to the small sample size of this proof-of-concept study, no formal statistical analysis was performed. |
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Notes [2] - Patient with revised diagnosis not included. |
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No statistical analyses for this end point |
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End point title |
CAS OD at 6 weeks | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
6 weeks
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Statistical analysis title |
Paired t-test (relative to baseline) | ||||||||||||
Comparison groups |
Nanocort v CAS
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
CAS OS at 6 weeks | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
6 weeks
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Statistical analysis title |
Paired t-test (relative to baseline) | ||||||||||||
Comparison groups |
Nanocort v CAS
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
CAS OD at 13 weeks | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
13 weeks
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Statistical analysis title |
Paired t-test (relative to baseline) | ||||||||||||
Comparison groups |
Nanocort v CAS
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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End point title |
CAS OS at 13 weeks | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
13 weeks
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Statistical analysis title |
Paired t-test (relative to baseline) | ||||||||||||
Comparison groups |
Nanocort v CAS
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Number of subjects included in analysis |
20
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
t-test, 2-sided | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
At the time of infusion, and at 13 weeks.
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Adverse event reporting additional description |
Orbital allergic response.
Non-responder.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21
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Reporting groups
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Reporting group title |
Nanocort
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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? Yes | |||
Date |
Amendment |
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11 Jan 2018 |
Inclusion criteria adapted. |
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05 Nov 2018 |
Update IMPD due to expired IMP. |
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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. | |||
None reported | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/33423386 |