Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II Study to Assess the Efficacy and Safety of Filgotinib Administered for 12 Weeks to Subjects With Active Ankylosing Spondylitis
Summary
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EudraCT number |
2016-003636-21 |
Trial protocol |
EE CZ ES BG BE |
Global end of trial date |
02 Jul 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Apr 2019
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First version publication date |
24 Apr 2019
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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 |
GLPG0634-CL-223
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03117270 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Study Acronym: TORTUGA | ||
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 15342 900, rd@glpg.com
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Scientific contact |
Clinical Trial Information Desk, Galapagos NV, +32 15342 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 |
31 Jan 2019
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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 |
02 Jul 2018
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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:
- Evaluate the effect of filgotinib 200 mg once daily compared with placebo once daily on the signs and symptoms of ankylosing spondylitis (AS), as assessed by the ankylosing spondylitis disease activity score (ASDAS) at Week 12
Secondary Objectives:
- Evaluate the effect of filgotinib 200 mg compared with placebo on:
- The signs and symptoms of AS
- Physical function
- Spinal mobility
- Spinal and sacroiliac joint inflammation
- Enthesitis
- Quality of life
- Evaluate the safety and tolerability of filgotinib 200 mg
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Protection of trial subjects |
This study was conducted in accordance with recognized international scientific and ethical standards including, but not limited to, the International Council for Harmonisation (ICH) guideline for Good Clinical Practice (GCP) (Sections 7.6 and 8.2), and the original principles embodied in the Declaration of Helsinki. These standards are consistent with the requirements of the European Community Directive 2001/20/EC. For Ukraine, standards were in accordance with Ukraine Guidance “Medicinal Products. Good clinical practice ССТ-Н МОЗУ 42-7.0:2008” approved by Ministry of Health Order of 16 February 2009 No. 95 and with consideration of requirements of Directive 2001/20/EC.
Investigators (or designee[s]) were responsible for obtaining written informed consent from each individual who participated in this study after adequate explanation of the aims, methods, objectives, and potential hazards of the study and before undertaking any study-related procedures. Participants were informed that they were completely free to refuse to enter the study or to withdraw from it at any time for any reason.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Mar 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 |
Ukraine: 64
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Country: Number of subjects enrolled |
Poland: 12
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Country: Number of subjects enrolled |
Spain: 6
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Country: Number of subjects enrolled |
Belgium: 2
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Country: Number of subjects enrolled |
Bulgaria: 24
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Country: Number of subjects enrolled |
Czech Republic: 6
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Country: Number of subjects enrolled |
Estonia: 2
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Worldwide total number of subjects |
116
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EEA total number of subjects |
52
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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) |
115
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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 |
Participants were enrolled at study sites in Europe. The first participant was screened on 07 March 2017. The last study visit occurred on 02 July 2018. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
263 subjects were screened, of whom 116 were randomized and received at least 1 dose of study drug. | |||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall study (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, Carer, Assessor | |||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Filgotinib 200 mg | |||||||||||||||||||||||||||
Arm description |
Participants received filgotinib 200 mg tablet orally once daily for 12 weeks. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Filgotinib
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Investigational medicinal product code |
GLPG0634
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received filgotinib 200 mg tablet orally once daily for 12 weeks.
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Participants received placebo to match filgotinib tablet orally once daily for 12 weeks. | |||||||||||||||||||||||||||
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 |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received placebo to match filgotinib tablet orally once daily for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Filgotinib 200 mg
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Reporting group description |
Participants received filgotinib 200 mg tablet orally once daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo to match filgotinib tablet orally once daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Filgotinib 200 mg
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Reporting group description |
Participants received filgotinib 200 mg tablet orally once daily for 12 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo to match filgotinib tablet orally once daily for 12 weeks. |
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End point title |
Change From Baseline in the Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12 | ||||||||||||||||||
End point description |
The ASDAS is a composite score of 5 domains: total back pain rated on a 0 to 10 numeric rating scale (NRS) (0 = not severe and 10 = very severe); patient’s global assessment of disease activity (PGADA) rated on a 0 to 10 NRS (0 = not active and 10 = very active); peripheral joint pain and/or swelling rated on a 0 to 10 NRS (0 = not severe and 10 = very severe); duration of morning stiffness rated on a 0 to 10 NRS (0 = 0 hours and 10 = 2 or more hours); high-sensitivity C-reactive protein (hsCRP) in mg/L (if hsCRP was nonmissing and < 2 mg/L, 2 mg/L was used in calculation).
ASDAS = 0.121 × (total back pain) + 0.110 × (PGADA) + 0.073 × (peripheral joint pain and/or swelling) + 0.058 × (duration of morning stiffness) + 0.579 × Ln(max[hsCRP, 2] + 1).
The ASDAS has a continuous scale starting from 0 with no defined upper end. A higher score indicated higher disease activity.
The Full Analysis Set included all randomized participants who received at least 1 dose of study drug.
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End point type |
Primary
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End point timeframe |
Baseline, Week 12
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Notes [1] - Missing values were imputed using the Last Observation Carried Forward (LOCF) method. [2] - Missing values were imputed using the Last Observation Carried Forward (LOCF) method. |
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Statistical analysis title |
Change in ASDAS at Week 12 | ||||||||||||||||||
Statistical analysis description |
Analysis of covariance (ANCOVA) model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
< 0.0001 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
Least-Squares (LS) Mean Difference | ||||||||||||||||||
Point estimate |
-0.85
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-1.17 | ||||||||||||||||||
upper limit |
-0.53 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.16
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End point title |
Percentage of Participants Achieving Assessment of Spondylo Arthritis international Society (ASAS)20 Response at Week 12 | ||||||||||||
End point description |
The ASAS20 response was defined as at least 20% improvement and at least 1-unit improvement in at least 3 out of 4 domains, and no worsening by at least 20% and at least 1 unit in the remaining domain. The 4 domains used were: PGADA rated on a 0 to 10 NRS (0 = not active and 10 = very active); patient’s assessment of spinal pain (PASP) rated on a 0 to 10 NRS (0 = no pain and 10 = most severe pain); bath ankylosing spondylitis functional index (BASFI) that rated physical functioning on a 0 to 10 NRS (0 = easy and 10 = impossible); and morning stiffness intensity and duration rated on a 0 to 10 NRS (0 = not severe or 0 hours and 10 = very severe or ≥ 2 hours). The 95% confidence interval (CI) for response rate was computed using the Wilson method.
The participants in Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 12
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Statistical analysis title |
ASAS20 Response Rate at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
36.2
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
18.35 | ||||||||||||
upper limit |
50.97 |
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End point title |
Percentage of Participants Achieving ASAS40 Response at Week 12 | ||||||||||||
End point description |
The ASAS40 response was defined as at least 40% improvement and at least 2-unit improvement in at least 3 out of 4 domains, and no worsening at all in the remaining domain. The 4 domains used were: PGADA rated on a 0 to 10 NRS (0 = not active and 10 = very active); PASP rated on a 0 to 10 NRS (0 = no pain and 10 = most severe pain); BASFI that rated physical functioning on a 0 to 10 NRS (0 = easy and 10 = impossible); and morning stiffness intensity and duration rated on a 0 to 10 NRS (0 = not severe or 0 hours and 10 = very severe or ≥ 2 hours). The 95% CI for response rate was computed using the Wilson method.
The participants in Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 12
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Statistical analysis title |
ASAS40 Response Rate at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.0189 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
18.9
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
2.52 | ||||||||||||
upper limit |
34.13 |
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End point title |
Percentage of Participants Achieving ASAS5/6 Response at Week 12 | ||||||||||||
End point description |
The ASAS5/6 response was defined as at least 20% improvement in at least 5 out of 6 domains. The 6 domains used were: PGADA rated on a 0 to 10 NRS (0 = not active and 10 = very active); PASP rated on a 0 to 10 NRS (0 = no pain and 10 = most severe pain); BASFI that rated physical functioning on a 0 to 10 NRS (0 = easy and 10 = impossible); morning stiffness intensity and duration rated on a 0 to 10 NRS (0 = not severe or 0 hours and 10 = very severe or ≥ 2 hours); lateral spinal flexion (measured in cm with higher value = improvement); and hsCRP (higher value = worsening). The 95% CI for response rate was computed using the Wilson method.
The participants in Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 12
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Statistical analysis title |
ASAS5/6 Response Rate at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
37.9
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
20.31 | ||||||||||||
upper limit |
52.4 |
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End point title |
Percentage of Participants Achieving ASAS Partial Remission (ASASPR) Response at Week 12 | ||||||||||||
End point description |
The ASASPR response was defined as achieving a value of not above 2 in each of 4 domains. The 4 domains used were: PGADA rated on a 0 to 10 NRS (0 = not active and 10 = very active); PASP rated on a 0 to 10 NRS (0 = no pain and 10 = most severe pain); BASFI that rated physical functioning on a 0 to 10 NRS (0 = easy and 10 = impossible); and morning stiffness intensity and duration rated on a 0 to 10 NRS (0 = not severe or 0 hours and 10 = very severe or ≥ 2 hours). The 95% CI for response rate was computed using the Wilson method.
The participants in Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 12
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Statistical analysis title |
ASASPR Response Rate at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
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Comparison groups |
Placebo v Filgotinib 200 mg
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.1028 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
8.7
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.66 | ||||||||||||
upper limit |
19.72 |
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End point title |
Change From Baseline in the Tender Joint Count of 44 Joints (TJC44) at Week 12 | ||||||||||||||||||
End point description |
Each of the following 44 joints were evaluated for tenderness: 2 sternoclavicular joints (left and right); 2 acromioclavicular joints (left and right); 2 shoulder joints (left and right); 2 elbows (left and right); 2 wrists (left and right); 10 metacarpophalangeal joints (left and right); 10 proximal interphalangeal joints (hands) (left and right); 2 knees (left and right); 2 ankles (left and right); 10 metatarsophalangeal joints (left and right). The tender joint count was done by scoring the presence or absence of tenderness as assessed by pressure and joint manipulation on physical examination. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set with ≥ 1 tender joint at baseline were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Change in TJC44 at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
88
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0849 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-0.79
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-1.68 | ||||||||||||||||||
upper limit |
0.11 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.45
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End point title |
Change From Baseline in the Swollen Joint Count of 44 Joints (SJC44) at Week 12 | ||||||||||||||||||
End point description |
Each of the following 44 joints were evaluated for swelling: 2 sternoclavicular joints (left and right); 2 acromioclavicular joints (left and right); 2 shoulder joints (left and right); 2 elbows (left and right); 2 wrists (left and right); 10 metacarpophalangeal joints (left and right); 10 proximal interphalangeal joints (hands) (left and right); 2 knees (left and right); 2 ankles (left and right); 10 metatarsophalangeal joints (left and right). Synovial fluid and/or soft tissue swelling, but not bony overgrowth, represented a positive result for swollen joint count. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set with ≥ 1 swollen joint at baseline were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Change in SJC44 at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.1779 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-0.31
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-0.76 | ||||||||||||||||||
upper limit |
0.15 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.22
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End point title |
Percentage of Participants Achieving Clinically Meaningful Improvement (CMI) (Decrease of ASDAS From Baseline ≥ 1.1) at Week 12 | ||||||||||||
End point description |
The CMI was defined as a decrease in ASDAS from baseline of ≥ 1.1 points. The ASDAS is a composite score of 5 domains: total back pain (0 to 10 NRS, 0 = not severe and 10 = very severe); PGADA (0 to 10 NRS, 0 = not active and 10 = very active); peripheral joint pain and/or swelling (0 to 10 NRS, 0 = not severe and 10 = very severe); duration of morning stiffness (0 to 10 NRS, 0 = 0 hours and 10 = 2 or more hours); hsCRP in mg/L.
ASDAS = 0.121 × (total back pain) + 0.110 × (PGADA) + 0.073 × (peripheral joint pain and/or swelling) + 0.058 × (duration of morning stiffness) + 0.579 × Ln(max[hsCRP, 2] + 1).
The ASDAS has a continuous scale starting from 0 with no defined upper end. A higher score indicated higher disease activity. The 95% CI for response rate was computed using the Wilson method.
The participants in Full Analysis Set with baseline ASDAS value ≥ 1.1 were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
CMI at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
|
||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
39.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
21.72 | ||||||||||||
upper limit |
54.14 |
|
|||||||||||||
End point title |
Percentage of Participants Achieving Major Improvement (MI) (Decrease of ASDAS From Baseline ≥ 2.0) at Week 12 | ||||||||||||
End point description |
The MI was defined as a decrease in ASDAS from baseline of ≥ 2.0 points. The ASDAS is a composite score of 5 domains: total back pain (0 to 10 NRS, 0 = not severe and 10 = very severe); PGADA (0 to 10 NRS, 0 = not active and 10 = very active); peripheral joint pain and/or swelling (0 to 10 NRS, 0 = not severe and 10 = very severe); duration of morning stiffness (0 to 10 NRS, 0 = 0 hours and 10 = 2 or more hours); hsCRP in mg/L.
ASDAS = 0.121 × (total back pain) + 0.110 × (PGADA) + 0.073 × (peripheral joint pain and/or swelling) + 0.058 × (duration of morning stiffness) + 0.579 × Ln(max[hsCRP, 2] + 1).
The ASDAS has a continuous scale starting from 0 with no defined upper end. A higher score indicated higher disease activity. The 95% CI for response rate was computed using the Wilson method.
The participants in Full Analysis Set with baseline ASDAS value ≥ 2.0 were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
MI at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
|
||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
31.1
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
18.04 | ||||||||||||
upper limit |
43.93 |
|
|||||||||||||
End point title |
Percentage of Participants Achieving Inactive Disease (ID) (ASDAS <1.3) at Week 12 | ||||||||||||
End point description |
The ID was defined as an ASDAS value < 1.3. The ASDAS is a composite score of 5 domains: total back pain (0 to 10 NRS, 0 = not severe and 10 = very severe); PGADA (0 to 10 NRS, 0 = not active and 10 = very active); peripheral joint pain and/or swelling (0 to 10 NRS, 0 = not severe and 10 = very severe); duration of morning stiffness (0 to 10 NRS, 0 = 0 hours and 10 = 2 or more hours); hsCRP in mg/L.
ASDAS = 0.121 × (total back pain) + 0.110 × (PGADA) + 0.073 × (peripheral joint pain and/or swelling) + 0.058 × (duration of morning stiffness) + 0.579 × Ln(max[hsCRP, 2] + 1).
The ASDAS has a continuous scale starting from 0 with no defined upper end. A higher score indicated higher disease activity. The 95% CI for response rate was computed using the Wilson method.
The participants in Full Analysis Set with baseline ASDAS value ≥ 1.3 were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
ID at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
|
||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0921 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
5.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-1.91 | ||||||||||||
upper limit |
14.14 |
|
|||||||||||||
End point title |
Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50% Response (BASDAI50) at Week 12 | ||||||||||||
End point description |
The BASDAI is a 6-item index (fatigue, spinal pain, peripheral arthritis, enthesitis, intensity and duration of morning stiffness) in which the items were rated on a 0 to 10 NRS (0 = none or 0 hour and 10 = very severe or ≥ 2 hours). The BASDAI total score = (Q1 + Q2 + Q3 + Q4 + [(Q5 + Q6)/2])/5. The BASDAI total score ranged from 0 to 10, with a higher score indicating more severe disease activity. The BASDAI50 response was defined as a decrease in BASDAI total score from baseline of ≥ 50%. The 95% CI for response rate was computed using the Wilson method.
The participants in Full Analysis Set were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
BASDAI50 Response Rate at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
|
||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.1134 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
10.3
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.08 | ||||||||||||
upper limit |
24.4 |
|
|||||||||||||
End point title |
Percentage of Participants Achieving ≥ 2 Units Improvement in BASDAI Total Score From Baseline at Week 12 | ||||||||||||
End point description |
The BASDAI is a 6-item index (fatigue, spinal pain, peripheral arthritis, enthesitis, intensity and duration of morning stiffness) in which the items were rated on a 0 to 10 NRS (0 = none or 0 hour and 10 = very severe or ≥ 2 hours). The BASDAI total score = (Q1 + Q2 + Q3 + Q4 + [(Q5 + Q6)/2])/5. The BASDAI total score ranged from 0 to 10, with a higher score indicating more severe disease activity. Percentage of participants achieving ≥ 2 units improvement in BASDAI from baseline at different time points was reported. The 95% CI for response rate was computed using the Wilson method.
The participants in Full Analysis Set with baseline BASDAI value ≥ 2 were analyzed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
BASDAI ≥ 2 units improvement at Week 12 | ||||||||||||
Statistical analysis description |
Cochran-Mantel-Haenszel test for general association, controlling for randomization stratification factors was used for the calculation of between-group p-value. 95% CI for the difference in response rate was computed using the Newcombe method.
|
||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.0025 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Response Rate Difference | ||||||||||||
Point estimate |
27.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
9.49 | ||||||||||||
upper limit |
43.29 |
|
|||||||||||||||||||
End point title |
Change From Baseline in BASDAI Total Score at Week 12 | ||||||||||||||||||
End point description |
The BASDAI is a 6-item index (fatigue, spinal pain, peripheral arthritis, enthesitis, intensity and duration of morning stiffness) in which the items were rated on a 0 to 10 NRS (0 = none or 0 hour and 10 = very severe or ≥ 2 hours). The BASDAI total score = (Q1 + Q2 + Q3 + Q4 + [(Q5 + Q6)/2])/5. The BASDAI total score ranged from 0 to 10, with a higher score indicating more severe disease activity. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set were analyzed.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Change in BASDAI Total Score at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
|
||||||||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0052 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-1
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-1.69 | ||||||||||||||||||
upper limit |
-0.3 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.35
|
|
|||||||||||||||||||
End point title |
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 12 | ||||||||||||||||||
End point description |
The BASFI total score was calculated as the average of 10 items (putting on socks, bending, reaching up, 2 items on getting up, standing, climbing steps, looking over shoulder, physical demanding activities, and full day’s activities) that were rated on a 0 to 10 NRS (0 = easy and 10 = impossible). The BASFI total score ranged from 0 to 10, with a higher BASFI indicating a higher level of functional impairment. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set were analyzed.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Change in BASFI Total Score at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
|
||||||||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
116
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0015 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-1.11
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-1.78 | ||||||||||||||||||
upper limit |
-0.43 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.34
|
|
|||||||||||||||||||
End point title |
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) Total Score at Week 12 | ||||||||||||||||||
End point description |
The BASMI total score was calculated as the average of 5 items (lateral spinal flexion, tragus-to-wall distance, lumber flexion [modified Schober], maximal intermalleolar distance, and cervical rotation). The unit for the first 4 items was ‘cm’, the unit for cervical rotation was ‘degree’. Each item outcome was converted to score ranging from 0 to 10. The BASMI total score ranged from 0 to 10, with a higher score indicating a more severe limitation of movement due to ankylosing spondylitis. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set with available data were analyzed.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Change in BASMI Total Score at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
|
||||||||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
114
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0093 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-0.39
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-0.68 | ||||||||||||||||||
upper limit |
-0.1 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.15
|
|
|||||||||||||||||||
End point title |
Change From Baseline in Chest Expansion at Week 12 | ||||||||||||||||||
End point description |
Chest expansion was measured as the difference between maximal inspiration and maximal forced expiration at the fourth intercostal space (in cm). The better of 2 assessments was reported. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set with available data were analyzed.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Change in Chest Expansion at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
|
||||||||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
114
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0254 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
0.53
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
0.07 | ||||||||||||||||||
upper limit |
0.99 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.23
|
|
|||||||||||||||||||
End point title |
Change From Baseline in Occiput-To-Wall Distance at Week 12 | ||||||||||||||||||
End point description |
Occiput-to-wall distance was measured as the distance (in cm) between the occiput and the wall with the participant’s heels and back rested against the wall. The better of 2 assessments was reported. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set with available data were analyzed.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||||
|
|||||||||||||||||||
Statistical analysis title |
Change in Occiput-To-Wall Distance at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
|
||||||||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||||||||
Number of subjects included in analysis |
114
|
||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.6141 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-0.38
|
||||||||||||||||||
Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||
lower limit |
-1.85 | ||||||||||||||||||
upper limit |
1.1 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||
Dispersion value |
0.74
|
|
|||||||||||||||||||||||||
End point title |
Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score at Week 12 | ||||||||||||||||||||||||
End point description |
The MRI images of the spine and sacroiliac joints were scored by a central reader using the SPARCC scoring system. Spine lesions were scored in all 23 spinal discovertebral units and total scores were provided. The maximal score for each discovertebral unit was 18, so the maximum SPARCC spine total score was 18 × 23 = 414. Sacroiliac joints were scored using 6 consecutive coronal slices from posterior to anterior. The maximal score for a single coronal slice was 12, so the maximum SPARCC sacroiliac joint total score was 12 × 6 = 72.
The participants in Full Analysis Set with available data were analyzed.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Statistical analysis title |
Change in Spine Lesions SPARCC MRI at Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value. Actual number of subjects included in this analysis = 89.
|
||||||||||||||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
109
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0066 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||||||||
Point estimate |
-5.69
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-9.75 | ||||||||||||||||||||||||
upper limit |
-1.62 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
2.04
|
||||||||||||||||||||||||
Statistical analysis title |
Change in Sacroiliac Joints SPARCC MRI at Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value. Actual number of subjects included in this analysis = 90.
|
||||||||||||||||||||||||
Comparison groups |
Filgotinib 200 mg v Placebo
|
||||||||||||||||||||||||
Number of subjects included in analysis |
109
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.015 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||||||||
Point estimate |
-2.33
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-4.2 | ||||||||||||||||||||||||
upper limit |
-0.46 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.94
|
|
|||||||||||||||||||
End point title |
Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Week 12 | ||||||||||||||||||
End point description |
The MASES assessed the enthesitis disease status in 13 sites: costochondral 1 right/left, costochondral 7 right/left, spina iliaca anterior superior right/left, crista iliaca right/left, spina iliaca posterior right/left, processus spinosus L5, Achilles tendon, proximal insertion right/left. Each site was categorized as: permanently not assessable, temporarily not assessable, asymptomatic, and tender only. Both “permanently not assessable” and “temporarily not assessable” were considered as missing assessments. For each non-missing site, a score of 1 was assigned for “tender only” and a score of 0 otherwise. The MASES was calculated as the sum of the scores of the 13 sites and ranged from 0 to 13. A higher score indicated a higher level of enthesitis.
Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set with enthesitis at baseline were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Change in MASES at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
95
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.6012 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
0.25
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-0.7 | ||||||||||||||||||
upper limit |
1.2 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.48
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End point title |
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Total Score at Week 12 | ||||||||||||||||||
End point description |
The FACIT-Fatigue scale consisted of 13 items, each scored on a 5-point scale (0 = not at all to 4 = very much). The larger the participant's response to the questions (with the exception of 2 negatively stated that are scored reversely), the greater the fatigue. The sum of all responses resulted in the FACIT-Fatigue total score that ranged from 0 (worse score) to 52 (better score), with a higher score indicating a better quality of life. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Change in FACIT-Fatigue Total Score at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0422 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
3.44
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
0.12 | ||||||||||||||||||
upper limit |
6.75 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.67
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End point title |
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Summary Scores at Week 12 | ||||||||||||||||||||||||
End point description |
The SF-36 questionnaire consisted of 36 questions divided over 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health), with each domain score ranging from 0 (worst) to 100 (best), and higher scores reflecting better health-related functional status. Two summary scores (Mental Component Summary [MCS] and Physical Component Summary [PCS]) were computed based on weighted combinations of the 8 domain scores. The summary scores were standardized to score ranging from 0 to 100 using the SF-36’s recalibration software, with higher scores indicated a better quality of life. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Change in SF36-MCS at Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
116
|
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0703 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||||||||
Point estimate |
2.54
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-0.21 | ||||||||||||||||||||||||
upper limit |
5.29 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.39
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Statistical analysis title |
Change in SF36-PCS at Week 12 | ||||||||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.0008 | ||||||||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||||||||
Point estimate |
4.41
|
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Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
1.88 | ||||||||||||||||||||||||
upper limit |
6.93 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
1.27
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End point title |
Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) Total Score at Week 12 | ||||||||||||||||||
End point description |
The ASQoL consisted of 18 yes/no questions, with 1 point assigned for each ‘yes’ response. The ASQoL total score was the sum of the 18 items and ranged from 0 to 18. A lower score indicated a better quality of life. Baseline value was the last non-missing value on or prior to first dose date of study drug. Missing values were imputed using the LOCF method.
The participants in Full Analysis Set were analyzed.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Change in ASQoL Total Score at Week 12 | ||||||||||||||||||
Statistical analysis description |
ANCOVA model with factors for treatment, baseline value, and randomization stratification was used for the calculation of between-group p-value.
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Comparison groups |
Filgotinib 200 mg v Placebo
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Number of subjects included in analysis |
116
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||
P-value |
= 0.0038 | ||||||||||||||||||
Method |
ANCOVA | ||||||||||||||||||
Parameter type |
LS Mean Difference | ||||||||||||||||||
Point estimate |
-2.35
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Confidence interval |
|||||||||||||||||||
level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-3.92 | ||||||||||||||||||
upper limit |
-0.77 | ||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.79
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 12 plus 30 days
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Adverse event reporting additional description |
The Safety Analysis Set included all participants who received at least 1 dose of study drug. The threshold of 3.4% applied for reporting non-serious adverse events corresponds to 2 subjects in a group.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
Filgotinib 200 mg
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Reporting group description |
Participants received filgotinib 200 mg tablet orally once daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received placebo to match filgotinib tablet orally once daily for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 3.4% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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30 Jun 2017 |
The benefit-risk assessment was updated based on clinical information regarding serious infections, lymphoma, and other malignancies, in accordance with the current version of the Investigator’s Brochure (Edition 12, dated 22 May 2017). Also, an optional substudy was added, requiring a separate consent, in which urine and stool samples were to be collected for biomarker analysis. In addition, minor corrections, clarifications, and wording changes were made. |
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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 |