Clinical Trial Results:
Intestinal Inflammation in Ankylosing Spondylitis assessed by Fecal Calprotectin, Capsular Endoscopy and Colonoscopy and the effects of Adalimumab on mucosal healing
Summary
|
|
EudraCT number |
2009-018085-35 |
Trial protocol |
DK |
Global end of trial date |
11 Mar 2014
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
26 Mar 2016
|
First version publication date |
26 Mar 2016
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
4682724
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01174186 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
|
|||
Sponsor organisation name |
Regionshospitalet Silkeborg
|
||
Sponsor organisation address |
Falkevej 1, Silkeborg, Denmark, 8220
|
||
Public contact |
Studieledelse, Regionshospitalet Silkeborg, +45 87222360, henngler@rm.dk
|
||
Scientific contact |
Studieledelse, Regionshospitalet Silkeborg, +45 87222360, henngler@rm.dk
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
09 Mar 2016
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
11 Mar 2014
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
11 Mar 2014
|
||
Was the trial ended prematurely? |
No
|
||
General information about the trial
|
|||
Main objective of the trial |
To establish the proportion of otherwise intestinally low-symptomatic patients with intestinal ulcers in patients diagnosed with active spondyloarthritis and to illustrate the healing rate following treatment with the TNF-alpha inhibitor adalimumab
|
||
Protection of trial subjects |
The patients were informed orally and in writing. During the trial the patients could call a phone number day and night with questions.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Oct 2010
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Denmark: 30
|
||
Worldwide total number of subjects |
30
|
||
EEA total number of subjects |
30
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
30
|
||
From 65 to 84 years |
0
|
||
85 years and over |
0
|
|
||||||||||||||||||||||
Recruitment
|
||||||||||||||||||||||
Recruitment details |
Patients were recruited from the rheumatologic outpatient clinics in the Central and North Denmark Regions on the basis of SpA activity. Patients ≥18 years with active SpA defined by expert opinion and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 (and thus candidates for anti-TNF treatment) were eligible for inclusion and were a | |||||||||||||||||||||
Pre-assignment
|
||||||||||||||||||||||
Screening details |
Because NSAID can elevate fecal calprotectin, patients were subjected to a 4-week NSAID washout period, after which fecal calprotectin was measured. Depending on the fecal calprotectin level the patients were grouped into either a “calprotectin normal” (<50 mg/kg) or “calprotectin high” (≥100 mg/kg) category. | |||||||||||||||||||||
Pre-assignment period milestones
|
||||||||||||||||||||||
Number of subjects started |
31 [1] | |||||||||||||||||||||
Number of subjects completed |
30 | |||||||||||||||||||||
Pre-assignment subject non-completion reasons
|
||||||||||||||||||||||
Reason: Number of subjects |
Consent withdrawn by subject: 1 | |||||||||||||||||||||
Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: One patient gave consent to join the study but withdrew his consent before completing NSAID wash-out period |
||||||||||||||||||||||
Period 1
|
||||||||||||||||||||||
Period 1 title |
overall trial (overall period)
|
|||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
|||||||||||||||||||||
Blinding used |
Not blinded | |||||||||||||||||||||
Arms
|
||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||
Arm title
|
Calprotectin high | |||||||||||||||||||||
Arm description |
calprotectin high: Fecal calprotectin ≥100 mg/kg after NSAID wash-out period | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Adalimumab
|
|||||||||||||||||||||
Investigational medicinal product code |
PR1
|
|||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled injector, Solution for injection in pre-filled syringe
|
|||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||
Dosage and administration details |
Loading dose of 80 mg. Hereafter 40 mg every other week
|
|||||||||||||||||||||
Arm title
|
Calprotectin normal | |||||||||||||||||||||
Arm description |
Faecal calprotectin <50 mg/kg after wash-out period | |||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||
Investigational medicinal product name |
Adalimumab
|
|||||||||||||||||||||
Investigational medicinal product code |
PR1
|
|||||||||||||||||||||
Other name |
||||||||||||||||||||||
Pharmaceutical forms |
Solution for injection in pre-filled injector, Solution for injection in pre-filled syringe
|
|||||||||||||||||||||
Routes of administration |
Subcutaneous use
|
|||||||||||||||||||||
Dosage and administration details |
40 mg every other week
|
|||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Calprotectin high
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
calprotectin high: Fecal calprotectin ≥100 mg/kg after NSAID wash-out period | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Calprotectin normal
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Faecal calprotectin <50 mg/kg after wash-out period | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Follow-up baseline
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Follow-up endoscopy in patients with intestinal inflammation or elevated calprotectin at baseline
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Follow-up 20 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients with either elevated calprotectin at baseline or intestinal inflammation after 20 weeks of treatment
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Follow-up 12 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Patients with elevated calprotectin at baseline or intestinal inflammation at endoscopy
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
Calprotectin high
|
||
Reporting group description |
calprotectin high: Fecal calprotectin ≥100 mg/kg after NSAID wash-out period | ||
Reporting group title |
Calprotectin normal
|
||
Reporting group description |
Faecal calprotectin <50 mg/kg after wash-out period | ||
Subject analysis set title |
Follow-up baseline
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Follow-up endoscopy in patients with intestinal inflammation or elevated calprotectin at baseline
|
||
Subject analysis set title |
Follow-up 20 weeks
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients with either elevated calprotectin at baseline or intestinal inflammation after 20 weeks of treatment
|
||
Subject analysis set title |
Follow-up 12 weeks
|
||
Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients with elevated calprotectin at baseline or intestinal inflammation at endoscopy
|
|
||||||||||||||||
End point title |
Intestinal inflammation | |||||||||||||||
End point description |
Number of subjects at baseline with any intestinal ulceration
|
|||||||||||||||
End point type |
Primary
|
|||||||||||||||
End point timeframe |
Baseline
|
|||||||||||||||
|
||||||||||||||||
Statistical analysis title |
Intestinal inflammation between groups | |||||||||||||||
Comparison groups |
Calprotectin high v Calprotectin normal
|
|||||||||||||||
Number of subjects included in analysis |
30
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
equivalence | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | |||||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Lewis score at follow-up | ||||||||||||
End point description |
Follow-up endoscopy in patients with intestinal inflammation or elevated faecal calprotectin at baseline
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
After 20 weeks of treatment
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Follow-up endoscopy | ||||||||||||
Statistical analysis description |
Comparison of Lewis score from baseline to 20 weeks after treatment onset
|
||||||||||||
Comparison groups |
Follow-up baseline v Follow-up 20 weeks
|
||||||||||||
Number of subjects included in analysis |
32
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
< 0.01 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|
|||||||||||||||||
End point title |
Fecal calprotectin changes | ||||||||||||||||
End point description |
Changes in koncentration of calprotectin in faces
|
||||||||||||||||
End point type |
Primary
|
||||||||||||||||
End point timeframe |
Baseline, 12 weeks and 20 weeks of treatment
|
||||||||||||||||
|
|||||||||||||||||
Attachments |
Untitled (Filename: F-calpro.png) |
||||||||||||||||
Statistical analysis title |
Faecal calprotectin | ||||||||||||||||
Statistical analysis description |
Change in calprotectin koncentration over time
|
||||||||||||||||
Comparison groups |
Follow-up baseline v Follow-up 20 weeks v Follow-up 12 weeks
|
||||||||||||||||
Number of subjects included in analysis |
48
|
||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||
Analysis type |
equivalence | ||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||
Method |
ANOVA | ||||||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
MRI inflammation | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to 52 weeks of follow-up
|
||||||||||||
|
|||||||||||||
Attachments |
Untitled (Filename: MRI intasah.png) |
||||||||||||
Statistical analysis title |
MRI score between groups | ||||||||||||
Statistical analysis description |
Analysis of MRI scores between groups
|
||||||||||||
Comparison groups |
Calprotectin normal v Calprotectin high
|
||||||||||||
Number of subjects included in analysis |
27
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Confidence interval |
|||||||||||||
Statistical analysis title |
MRI score over time | ||||||||||||
Statistical analysis description |
Comparison of MRI scores before and after treatment
|
||||||||||||
Comparison groups |
Calprotectin high v Calprotectin normal
|
||||||||||||
Number of subjects included in analysis |
27
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
equivalence | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Report for serious adverse events made annually. Here reported for entire study period
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
ICD | |||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Calprotectin high
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
calprotectin high: Fecal calprotectin ≥100 mg/kg after NSAID wash-out period | |||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Calprotectin normal
|
|||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Faeacal calprotectin <50 mg/kg after wash-out period | |||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
||
19 May 2011 |
A comparator group (calprotectin normal) was added to the study. Based on included subjects inclusion number was changed to n=15 in each group |
||
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 |