Clinical Trial Results:
Phase II, Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of GLPG1205 in Patients with Moderate to Severe Ulcerative Colitis
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Summary
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EudraCT number |
2014-001893-32 |
Trial protocol |
CZ HU BE DE PL |
Global end of trial date |
09 Nov 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Nov 2016
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First version publication date |
24 Nov 2016
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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 |
GLPG1205-CL-211
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02337608 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Galapagos NV
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Sponsor organisation address |
Generaal De Wittelaan L11 A3, Mechelen, Belgium, 2800
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Public contact |
Clinical Trial Information Desk, Galapagos NV, +32 15 342 900, rd@glpg.com
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Scientific contact |
Clinical Trial Information Desk, Galapagos NV, +32 15 342 900, rd@glpg.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 |
01 Apr 2016
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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 |
09 Nov 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 |
Primary objective:
- To explore the efficacy of GLPG1205 versus placebo in subjects with UC by use of the Mayo score comparing results at Week 8 to baseline.
Secondary objectives:
- To explore the efficacy of GLPG1205 versus placebo in subjects with UC by use of the partial Mayo score comparing results with baseline.
- To explore the efficacy of GLPG1205 versus placebo in subjects with UC by use of the histopathological Geboes Index comparing results at Week 8 with baseline.
- To evaluate the safety and tolerability of GLPG1205 given to subjects with moderate to severe UC for 12 weeks compared with placebo.
- To characterize the PK of GLPG1205 in subjects with UC.
- To explore the effects of GLPG1205 on selected biomarkers (e.g., fecal calprotectin, myeloperoxidase (MPO), C-reactive protein [CRP]).
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Protection of trial subjects |
This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on
Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, this clinical study was conducted in compliance with all international and national laws and regulations, as
well as any applicable guidelines of the countries in which the clinical study was performed.
A signed and dated informed consent was required before any screen procedures were done. The Investigators were to explain the nature, purpose, and risks of the study to each subject. Each
subject was to be informed that he/she could withdraw from the study at any time and for any reason. Each subject was to be given sufficient time to consider the implications of the study before
deciding whether to participate. Subjects who chose to participate had to sign an informed consent document. A copy of the signed and dated written informed consent form (ICF) was to be provided to the subject.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Dec 2014
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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 |
Poland: 21
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Country: Number of subjects enrolled |
Belgium: 4
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Country: Number of subjects enrolled |
Czech Republic: 9
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Country: Number of subjects enrolled |
Germany: 7
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Country: Number of subjects enrolled |
Hungary: 6
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Country: Number of subjects enrolled |
Russian Federation: 16
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Worldwide total number of subjects |
63
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EEA total number of subjects |
47
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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) |
62
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were enrolled at study sites in Europe. The first participant was randomised on 17 December 2014. The last visit occurred on 9 November 2015. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
102 subjects were screened. | |||||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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GLPG1205 | |||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
GLPG1205
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Investigational medicinal product code |
G321605
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received 100 mg GLPG1205 (2 capsules of 50 mg) qd for 12 weeks.
The GLPG1205 capsules had to be taken orally with a glass of water in the morning.
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received 100 mg placebo (2 capsules of 50 mg) qd for 12 weeks.
The placebo capsules had to be taken orally with a glass of water in the morning.
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Baseline characteristics reporting groups
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Reporting group title |
GLPG1205
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
GLPG1205 change vs Baseline
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomized subjects who had at least 1 dose of study drug and had at least 1 post-baseline assessment with efficacy data.
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Subject analysis set title |
Placebo vs Baseline
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Mayo Score
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End points reporting groups
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Reporting group title |
GLPG1205
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Reporting group description |
- | ||
Reporting group title |
Placebo
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Reporting group description |
- | ||
Subject analysis set title |
GLPG1205 change vs Baseline
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All randomized subjects who had at least 1 dose of study drug and had at least 1 post-baseline assessment with efficacy data.
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Subject analysis set title |
Placebo vs Baseline
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Mayo Score
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End point title |
Efficacy: Mayo Score Week 8 | |||||||||||||||||||||||||
End point description |
The Mayo score equals the sum of the 4 subscores (stool frequency, rectal bleeding, physician's global assessment and Mayo endoscopic subscore) and therefore ranges from 0 to 12. A score of ≤ 2 is considered remission, a score of 3 to 5 is considered mild, a score of 6 to 10 is considered moderate, and a score of 11 to 12 is considered severe.
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End point type |
Primary
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End point timeframe |
Week 8
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Statistical analysis title |
Mayo score Week 8 | |||||||||||||||||||||||||
Comparison groups |
GLPG1205 v Placebo
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Number of subjects included in analysis |
61
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | |||||||||||||||||||||||||
P-value |
= 0.5005 | |||||||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||||||
Confidence interval |
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End point title |
Efficacy: Mayo Score: Derived Responses at Week 8 | ||||||||||||||||||||||||
End point description |
A summary of the Mayo clinical response, clinical remission, mucosal healing, and endoscopic response per treatment group at Week 8
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End point type |
Primary
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End point timeframe |
Week 8
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Statistical analysis title |
Mayo Score: derived responses at week 8 | ||||||||||||||||||||||||
Comparison groups |
GLPG1205 v Placebo
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Number of subjects included in analysis |
61
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | ||||||||||||||||||||||||
P-value |
= 0.6143 [1] | ||||||||||||||||||||||||
Method |
Regression, Logistic | ||||||||||||||||||||||||
Confidence interval |
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| Notes [1] - Mayo response (p-value=0.6143) Mayo remission (p-value=0.9084) Endoscopic response (p-value=0.1865) Mucosal healing (p-value=0.5519) There was no statistically significant difference between GLPG1205 and placebo. |
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End point title |
Efficacy: Partial Mayo Score | |||||||||||||||||||||||||||||||||||
End point description |
The Partial Mayo consists of the clinical components only of the MAYO only, namely stool frequency, rectal bleeding and physician's global assessment. Partial Mayo score ranges from 0 to 9, with higher scores indicating a more severe disease.
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End point type |
Secondary
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End point timeframe |
Week 4, 8, 12
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Efficacy: Geboes Index | |||||||||
End point description |
The Geboes Index is the highest grade with a sub-grade above 0 and ranges from 0.0 to 5.4, with higher scores indicating a more severe disease.
Scores: 0 = Structural (architectural change), 1 = Chronic inflammatory infiltrate, 2A = Lamina propria eosinophils, 2B = Lamina propria neutrophils, 3 = Neutrophils in epithelium, 4 = Cruypt destruction, 5 = Erosion or ulceration.
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End point type |
Secondary
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End point timeframe |
Week 8
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Attachments |
Untitled (Filename: Table 20 Week 8 Geboes Index Shift Table.pdf) |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Pharmacokinetics | |||||||||
End point description |
On average, the plasma concentration of GLPG1205 in subjects with UC were within the range of the GLPG1205 plasma concentrations seen in healthy subjects who were administered GLPG1205 100 mg qd. However, some subjects showed GLPG1205 plasma concentrations that were out of the range that was observed in healthy subjects who were administered GLPG1205 at the same dose of 100 mg qd.
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End point type |
Secondary
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End point timeframe |
A blood sample for analysis of GLPG1205 in blood plasma was collected at Week 4, 8 and 12
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| Notes [2] - Not applicable |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Pharmacodynamics: Fecal Calprotectin | |||||||||||||||||||||||||||||||||||
End point description |
A stool sample for the assessment of fecal calprotectin levels will be assessed as a marker for intestinal inflammatory activity.
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End point type |
Secondary
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End point timeframe |
Fecal calprotectin analysis on stool samples: Week 4, 8 and 12
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Pharmacodynamics: Myeloperoxidase Week 8 | ||||||||||||||||||||||||||||||
End point description |
Lamina Propria MPO Positive vs. Stromal (%)
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End point type |
Secondary
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End point timeframe |
Week 8
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Pharmacodynamics: serum C-reactive Protein (CRP) Week 4, 8, 12 | |||||||||||||||||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Week 4, 8, 12
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Safety: TEAE | |||||||||||||||
End point description |
(S)AE / TEAE: reference is made to the adverse events section.
The total number of subjects with at least one treatment-emergent adverse event (TEAE) was 9 (42.9%) subjects in the placebo group and 26 (61.9%) subjects in the GLPG1205 group.
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End point type |
Secondary
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End point timeframe |
From screening untill follow-up visit
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Safety: physical examination, vital signs, ECG, clinical laboratory | |||||||||
End point description |
There were no clinically meaningful trends in changes from baseline for any vital signs, ECG, or physical examination variables. There were no clinically relevant abnormalities reported on laboratory assessments. However, in the GLPG1205 group, there was a larger increase in creatinine compared to the placebo group.
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End point type |
Secondary
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End point timeframe |
Week 4, 8 , 12 and follow-up
for physical exam, no week 8
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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 screening until follow-up visit
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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 |
19.0
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Reporting groups
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Reporting group title |
GLPG1205
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Reporting group description |
The total number of subjects with at least one treatment-emergent adverse event (TEAE) was 26 (61.9%) subjects in the GLPG1205 group . In the GLPG1205 group, the highest number of subjects with TEAEs were observed the Gastrointestinal disorders SOC (11 [26.2%]), mainly with the preferred term (PT) of UC (4 [9.5%]) and nausea (3 [7.1%]). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
The total number of subjects with at least one treatment-emergent adverse event (TEAE) was 9 (42,9%) subjects in the placebo group. In the placebo group, the highest number of subjects with TEAEs came from the Gastrointestinal disorders SOC (3 [14.3%]) and Nervous system disorders SOC (3 [14.3%]). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 Nov 2014 |
The reasons for clinical study protocol amendment (CSPA) 1 were as follows:
- Updated the emergency contact email address.
- In the Risk Benefit section, the interaction with several CYPs was clarified and information about drug transporters was added.
- In the Removal from Subjects from Therapy Assessment section, the definition of disease worsening was added.
- In the Prior and Concomitant Therapy section, guidance on possible drug-drug interactions was added. |
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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 | |||
