Clinical Trial Results:
STRIKE – Treating Patients with Early Axial Spondyloarthritis to Target – a 1 Year Randomized Controlled Study Taking an Intense Treatment Approach Versus Routine Treatment
Summary
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EudraCT number |
2015-005398-18 |
Trial protocol |
DE |
Global end of trial date |
21 Dec 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Dec 2018
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First version publication date |
28 Dec 2018
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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 |
W15-679
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02897115 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Abbvie Deutschland GmbH & Co.KG
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Sponsor organisation address |
House, Vanwall Business Park, Maidenhead, Berkshire, United Kingdom, SL6-4UB
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Public contact |
Global Medical Services, Abbvie, 011 800-633-9110,
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Scientific contact |
Henning Kleine, Abbvie, henning.kleine@abbvie.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 |
21 Dec 2017
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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 |
21 Dec 2017
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to compare an intensified treat-to-target (T2T) treatment approach with standard of care (SOC) in reducing disease activity at Week 32 in patients with early axial spondyloarthritis (axSpA).
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Protection of trial subjects |
The study was conducted in accordance with the protocol, ICH guidelines, applicable regulations and guidelines governing clinical study conduct and the ethical principles that have their origin in the Declaration of Helsinki.
All subjects entering the study had to sign an informed consent that was explained to them and questions encouraged.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
12 Sep 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 22
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Worldwide total number of subjects |
22
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EEA total number of subjects |
22
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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) |
22
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study planned to enroll approximately 240 participants at 30 sites in Germany. Due to slow enrollment the study was terminated prematurely; At the time the decision to close the study was made 22 subjects were enrolled at 9 sites in Germany. | |||||||||||||||
Pre-assignment
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Screening details |
Twenty-six subjects were screened, 22 of whom were randomized. Four of the screened subjects were not randomized; one subject due to premature study termination by the sponsor, one subject withdrew consent during the screening period, and two subjects did not meet inclusion criteria. | |||||||||||||||
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 |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Treat-to-Target (T2T) | |||||||||||||||
Arm description |
Participants initially received treatment with any non-steroidal anti-inflammatory drug (NSAID) at full anti-inflammatory dose for 4 weeks. After 4 weeks, if the Ankylosing Spondylitis Disease Activity Score (ASDAS) was ≥ 2.1 or treatment with NSAID 1 was not tolerated, treatment was changed to a second NSAID at full anti-inflammatory dose for 4 weeks. If ASDAS was ≥ 2.1 after 4 weeks of NSAID 2, participants were switched to receive a combination of NSAID and adalimumab 40 mg every other week for up to 48 weeks. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Adamimumab
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Investigational medicinal product code |
ABT-D2E7
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Other name |
Humira
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Adalimumab 40 mg administered every other week by subcutaneous injection for up to 48 weeks, depending on participants' disease activity.
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Arm title
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Standard of Care (SOC) | |||||||||||||||
Arm description |
Participants received treatment as prescribed by their physician according to the local standard of care. | |||||||||||||||
Arm type |
Standard of Care | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Treat-to-Target (T2T)
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Reporting group description |
Participants initially received treatment with any non-steroidal anti-inflammatory drug (NSAID) at full anti-inflammatory dose for 4 weeks. After 4 weeks, if the Ankylosing Spondylitis Disease Activity Score (ASDAS) was ≥ 2.1 or treatment with NSAID 1 was not tolerated, treatment was changed to a second NSAID at full anti-inflammatory dose for 4 weeks. If ASDAS was ≥ 2.1 after 4 weeks of NSAID 2, participants were switched to receive a combination of NSAID and adalimumab 40 mg every other week for up to 48 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard of Care (SOC)
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Reporting group description |
Participants received treatment as prescribed by their physician according to the local standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treat-to-Target (T2T)
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Reporting group description |
Participants initially received treatment with any non-steroidal anti-inflammatory drug (NSAID) at full anti-inflammatory dose for 4 weeks. After 4 weeks, if the Ankylosing Spondylitis Disease Activity Score (ASDAS) was ≥ 2.1 or treatment with NSAID 1 was not tolerated, treatment was changed to a second NSAID at full anti-inflammatory dose for 4 weeks. If ASDAS was ≥ 2.1 after 4 weeks of NSAID 2, participants were switched to receive a combination of NSAID and adalimumab 40 mg every other week for up to 48 weeks. | ||
Reporting group title |
Standard of Care (SOC)
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Reporting group description |
Participants received treatment as prescribed by their physician according to the local standard of care. |
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End point title |
Percentage of Participants With an Ankylosing Spondylitis Disease Activity Score (ASDAS) of Inactive Disease at Week 32 [1] | ||||||||||||
End point description |
ASDAS inactive disease is defined as ASDAS < 1.3. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (C-reactive protein [CRP] or erythrocyte sedimentation rate [ESR]) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Primary
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End point timeframe |
Week 32
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The study terminated early due to slow enrollment and no data were analyzed. |
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Notes [2] - The study terminated early due to slow enrollment and no data were analyzed. [3] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Assessment of Spondyloarthritis International Society (ASAS) Health Index (HI) | ||||||||||||
End point description |
The ASAS HI measures functioning and health across 17 aspects of health in patients with AS, including pain, emotional functions, sleep, sexual function, mobility, self care, and community life. The ASAS HI consists of 17 questions, each answered by the participant as agree (1) or disagree (0). The responses to the 17 dichotomous items are summed up to give a total score ranging from 0 to 17, with a lower score indicating a better and a higher score indicating an inferior health status.
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [4] - The study terminated early due to slow enrollment and no data were analyzed. [5] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Work Productivity and Activity Impairment – Axial Spondyloarthritis (WPAI-axSpA) | ||||||||||||
End point description |
The Work Productivity and Activity Impairment (WPAI) axSpA is an axSpA specific questionnaire consisting of 6 questions, based on patient recall of the previous 7 days. WPAI assesses work time missed due to illness (absenteeism), impairment at work due to health (presenteeism), overall work impairment due to health (an aggregate measure of both absenteeism and presenteeism), and total non-occupational activity impairment due to health. WPAI scores are expressed as impairment percentages, with higher scores indicating worse outcomes. A negative change from baseline indicates improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [6] - The study terminated early due to slow enrollment and no data were analyzed. [7] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in European Quality of Life-5 Dimensions (EQ-5D) Questionnaire | ||||||||||||
End point description |
The EQ-5D-3L is a health state utility instrument that evaluates preference for health status (utility). The 5 items in the EQ-5D-3L comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on 3 levels of severity (1: indicating no problem, 2: indicating some/moderate problems, 3: indicating extreme problems). A single preference-weighted health utility index score was calculated by applying country-specific weights, with scores ranging from approximately 0 (death) to 1 (full health).
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [8] - The study terminated early due to slow enrollment and no data were analyzed. [9] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index | ||||||||||||
End point description |
The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) assesses disease activity by asking the participant to answer 6 questions (each on a 10 point numeric rating scale [NRS]) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10 where lower scores indicate less disease activity.
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [10] - The study terminated early due to slow enrollment and no data were analyzed. [11] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With ASDAS Low Disease Activity | ||||||||||||
End point description |
ASDAS low disease activity is defined as an ASDAS < 2.1. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Secondary
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End point timeframe |
Week 32 and week 52
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Notes [12] - The study terminated early due to slow enrollment and no data were analyzed. [13] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With ASDAS Moderate Disease Activity | ||||||||||||
End point description |
ASDAS moderate disease activity is defined as an ASDAS ≥ 1.3 to < 2.1. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Secondary
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End point timeframe |
Week 32 and week 52
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Notes [14] - The study terminated early due to slow enrollment and no data were analyzed. [15] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With ASDAS High Disease Activity | ||||||||||||
End point description |
ASDAS high disease activity is defined as an ASDAS ≥ 2.1 to < 3.5. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Secondary
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End point timeframe |
Week 32 and week 52
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Notes [16] - The study terminated early due to slow enrollment and no data were analyzed. [17] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Achieving ASDAS Clinically Important Improvement | ||||||||||||
End point description |
ASDAS clinically important improvement is defined as a change from baseline ≤ -1.1.
ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [18] - The study terminated early due to slow enrollment and no data were analyzed. [19] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Achieving ASDAS Major Improvement | ||||||||||||
End point description |
ASDAS Major Improvement is defined as a change from baseline ≤ -2.0. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [20] - The study terminated early due to slow enrollment and no data were analyzed. [21] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in ASDAS | ||||||||||||
End point description |
ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [22] - The study terminated early due to slow enrollment and no data were analyzed. [23] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) | ||||||||||||
End point description |
The Bath Ankylosing Spondylitis Functional Index (BASFI) is a validated index to determine the degree of functional limitation in patients with AS. BASFI consists of 10 questions assessing participants' ability to perform activities, on a numeric rating scale (NRS) ranging from 0 (easy to perform an activity) to 10 (impossible to perform an activity). The overall score is the mean of the 10 items and ranges from 0 (best) to 10 (worst).
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [24] - The study terminated early due to slow enrollment and no data were analyzed. [25] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With ASDAS Inactive Disease at Week 52 | ||||||||||||
End point description |
ASDAS inactive disease is defined as ASDAS < 1.3. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Secondary
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End point timeframe |
Week 52
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Notes [26] - The study terminated early due to slow enrollment and no data were analyzed. [27] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Achieving a BASDAI 50 Response | ||||||||||||
End point description |
The BASDAI assesses disease activity by asking the participant to answer 6 questions (each on a 10 point numeric rating scale [NRS]) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (≥ 2 hours). The overall BASDAI score ranges from 0 to 10. Lower scores indicate less disease activity.
A BASDAI 50 response is defined as improvement of 50% or more from baseline in BASDAI score.
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [28] - The study terminated early due to slow enrollment and no data were analyzed. [29] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants With ASDAS Very High Disease Activity | ||||||||||||
End point description |
ASDAS very high disease activity is defined as an ASDAS ≥ 3.5. ASDAS is a composite disease activity outcome measure which combines patient reported back pain, duration of morning stiffness, patient global assessment of disease activity, patient assessment of peripheral joint pain and swelling and an acute phase reactant (CRP or ESR) as an objective measure of inflammation. The overall score ranges from 0 with no defined upper score; published ranges for disease activity states as defined by the ASDAS are: < 1.3 for "inactive disease"; ≥ 1.3 to < 2.1 for "moderate disease activity"; ≥ 2.1 to ≤ 3.5 for "high disease activity" and > 3.5 for "very high disease activity."
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End point type |
Secondary
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End point timeframe |
Week 32 and week 52
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Notes [30] - The study terminated early due to slow enrollment and no data were analyzed. [31] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response | ||||||||||||
End point description |
ASAS20 response was defined as improvement of ≥ 20% relative to baseline and absolute improvement of ≥ 1 unit (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 unit) in the potential remaining domain:
• Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
• Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
• Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
• Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
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Notes [32] - The study terminated early due to slow enrollment and no data were analyzed. [33] - The study terminated early due to slow enrollment and no data were analyzed. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Achieving an ASAS 40 Response | ||||||||||||
End point description |
ASAS40 response was defined as improvement of ≥ 40% relative to baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration in the potential remaining domain:
• Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
• Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
• Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
• Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
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End point type |
Secondary
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End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [34] - The study terminated early due to slow enrollment and no data were analyzed. [35] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Percentage of Participants Achieving ASAS Partial Remission | ||||||||||||
End point description |
ASAS partial remission is defined as an absolute score of ≤ 2 units on a 0 to 10 scale for each of the four following domains:
• Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
• Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
• Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
• Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 32 and week 52
|
||||||||||||
|
|||||||||||||
Notes [36] - The study terminated early due to slow enrollment and no data were analyzed. [37] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Patient's Global Assessment of Pain | ||||||||||||
End point description |
The Patient's Global Assessment of Pain was assessed on a NRS from 0 (no pain) to 10 (pain as bad as it could be).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [38] - The study terminated early due to slow enrollment and no data were analyzed. [39] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Tender Joint Count | ||||||||||||
End point description |
An assessment of 68 joints was performed by physical examination of each joint. Joint pain/tenderness was classified as present (1), absent (0), replaced (9), or no assessment (NA).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [40] - The study terminated early due to slow enrollment and no data were analyzed. [41] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Patient's Global Assessment of Disease Activity | ||||||||||||
End point description |
The Patient's Global Assessment of Disease Activity was assessed using an NRS from 0 (no disease activity) to 10 (very severe disease activity).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [42] - The study terminated early due to slow enrollment and no data were analyzed. [43] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Physician's Global Assessment of Disease Activity | ||||||||||||
End point description |
The Physician's Global Assessment of Disease Activity was assessed using an NRS from 0 (no disease activity) to 10 (severe disease activity).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [44] - The study terminated early due to slow enrollment and no data were analyzed. [45] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Active Inflammation of the Sacroiliac Joints and Spine | ||||||||||||
End point description |
Active inflammation of the sacroiliac (SI) joints as well as the cervical, thoracic and lumbar regions of the spine was assessed using magnetic resonance imaging (MRI). Images were scored by a central reader according to the Berlin MRI Score on a grading scale from 0 to 3, where Grade 0 indicates no active inflammation and Grade 3 indicates > 66% inflammation of the sacroiliac joints or > 50% active inflammation in the spine.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline and week 52
|
||||||||||||
|
|||||||||||||
Notes [46] - The study terminated early due to slow enrollment and no data were analyzed. [47] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Swollen Joint Count | ||||||||||||
End point description |
An assessment of 66 joints was performed by physical examination of each joint. Joint swelling was classified as present (1), absent (0), replaced (9), or no assessment (NA).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [48] - The study terminated early due to slow enrollment and no data were analyzed. [49] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
ange From Baseline in Dactylitis Count | ||||||||||||
End point description |
Dactylitis is characterized by swelling of the entire finger or toe. Each digit on the hands and feet was rated as 0 for no dactylitis or 1 for dactylitis present. The dactylitis severity score is the sum of the individual scores for each digit. The dactylitis severity score, ranging from 0 to 20, is the number of digits on the hands and feet with dactylitis present.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [50] - The study terminated early due to slow enrollment and no data were analyzed. [51] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in C-reactive Protein (CRP) | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [52] - The study terminated early due to slow enrollment and no data were analyzed. [53] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in the Erythrocyte Sedimentation Rate (ESR) | ||||||||||||
End point description |
|||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [54] - The study terminated early due to slow enrollment and no data were analyzed. [55] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Number of Participants With New Onset Anterior Uveitis | |||||||||
End point description |
||||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Up to Week 52
|
|||||||||
|
||||||||||
Notes [56] - The study terminated early due to slow enrollment and no data were analyzed. [57] - The study terminated early due to slow enrollment and no data were analyzed. |
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) | ||||||||||||
End point description |
The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at 13 entheses (sites where tendons or ligaments insert into the bone). All sites were scored as 0 (absent) or 1 (present). The MASES is the sum of all site scores (from 0 to 13).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [58] - The study terminated early due to slow enrollment and no data were analyzed. [59] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin) | ||||||||||||
End point description |
The linear Bath Ankylosing Spondylitis Metrology Index (BASMIlin) is a composite score based on 5 direct measurements of spinal mobility: lateral lumbar flexion, tragus‐to‐wall distance, lumbar flexion, intermalleolar distance, and cervical rotation angle. The total score ranges from 0 to 10, where higher scores indicate more limited mobility.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 32, and week 52
|
||||||||||||
|
|||||||||||||
Notes [60] - The study terminated early due to slow enrollment and no data were analyzed. [61] - The study terminated early due to slow enrollment and no data were analyzed. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
Up to 52 weeks.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.1
|
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Reporting groups
|
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Reporting group title |
Standard of Care (SOC)
|
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Reporting group description |
Participants received treatment as prescribed by their physician according to the local standard of care. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treat-to-Target (T2T)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants initially received treatment with any non-steroidal anti-inflammatory drug (NSAID) at full anti-inflammatory dose for 4 weeks. After 4 weeks, if the Ankylosing Spondylitis Disease Activity Score (ASDAS) was ≥ 2.1 or treatment with NSAID 1 was not tolerated, treatment was changed to a second NSAID at full anti-inflammatory dose for 4 weeks. If ASDAS was ≥ 2.1 after 4 weeks of NSAID 2, participants were switched to receive a combination of NSAID and adalimumab 40 mg every other week for up to 48 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
24 Jun 2016 |
Key changes include:
• Updated Section 5.2.2, Exclusion criteria.
Rationale: Amended the criteria upon Ethics Committee’s request, to reflect that vulnerable subjects are not eligible to participate in the study.
• Updated Section 5.4.1, Discontinuation of Individual Subjects.
Rationale: Upon Ethics Committee’s request, provided more detailed clarification on the reasons for premature study discontinuation of individual subjects by cross-referencing to Section 6.1.7.
• Updated Section 5.4.2, Discontinuation of Entire Study.
Rationale: Upon Ethics Committee’s request, provided more detailed clarification on the reasons for premature study termination.
• Updated Section 6.1.7, Toxicity Management.
Rationale: Amended Section text with information on management of selected laboratory abnormalities. |
||
30 Mar 2017 |
The second protocol amendment was written to increase the number of sites to 30.
Key changes included:
• Updated Section 1.2, Synopsis.
Rationale: Added change in BASMIlin to secondary objectives in Objectives and Criteria for Evaluation subsections to align with Section 5.3.1, Table 1 – Study Activities; increased the number of participating study sites to allow for faster enrollment; and aligned the Statistical Methods subsection with the respective wording concerning the safety analyses in Section 8.1.6 of the protocol.
• Updated Section 5.1, Overall Study Design and Plan: Description, and Section 5.5.1, Treatments Administered.
Rationale: Provided clarification regarding NSAIDs to be used in case of escalation to Escalation Step 2 due to intolerance to NSAID 2.
• Updated Section 6.1, Medical Complaints.
Rationale: Changed Section title from ‘Adverse Events’ to ‘Medical Complaints’ to align with new protocol template.
• Updated Section 6.1.3, Relationship to Humira.
Rationale: Updated definitions of reasonable versus no reasonable possibility to align with new protocol template. |
||
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 |