A Study of Golimumab in Participants With Active Ankylosing Spondylitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of intravenously (administration of a fluid into the vein) administered golimumab 2 milligram per kilogram (mg/kg) in participants with active ankylosing spondylitis (chronic inflammatory disease of unknown etiology that involves the sacroiliac joints, and often the axial skeleton, entheses, and peripheral joints).

Detailed Description
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This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study drug assigned by chance), double-blind (neither the researchers nor the participants know what treatment the participant is receiving), placebo-controlled (an inactive substance; a pretend treatment [with no drug in it] that is compared in a clinical trial with a drug to test if the drug has a real effect) study of golimumab compared with placebo in participants with active ankylosing spondylitis. The study comprises of 4 phases: Screening phase (up to 6 weeks), Double-blind placebo-controlled phase (Week 0 to Week 16), Active treatment phase (Week 16 to Week 52), and Safety follow-up phase (8 weeks from last study drug administration). Total duration of the study will be 60 weeks per participant. Eligible Participants will be randomly assigned to either Treatment group 1: Placebo or Treatment group 2: Golimumab. Participants randomized to Placebo group, will receive intravenous infusions of placebo at Weeks 0, 4 and 12. At Week 16, all participants receiving placebo will begin receiving intravenous infusions of golimumab (2 mg/kg) at Weeks 16, 20 and thereafter every 8 weeks up to Week 52. Participants randomized to Golimumab group, will receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 16, participants randomized to golimumab group will receive a placebo infusion to maintain the blind. The efficacy will be assessed primarily by measuring percentage of participants who achieve a 20 percent improvement from baseline in the assessment in ankylosing spondylitis (ASAS) at Week 16. Participant's safety will be monitored throughout the study.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFα Monoclonal Antibody, Administered Intravenously, in Subjects With Active Ankylosing Spondylitis

Conditions
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Ankylosing Spondylitis

Intervention / Treatment
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* Drug: Placebo
* Drug: Golimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with diagnosis of definite ankylosing spondylitis for at least 3 months based on modified New York radiographic and clinical criteria Participants with symptoms of active disease at screening and at baseline Participant has either an inadequate response to at least 2 non-steroidal anti-inflammatory drugs (NSAID) over a 4 week period in total with maximal recommended doses of NSAIDs, or is unable to receive a full 4 weeks of maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs Participants with C- reactive protein (CRP) level of greater than or equal to (>=) 0.3 milligram per deciliter (mg/dL) at screening Additional protocol-defined inclusion criteria apply Exclusion Criteria: Participant with other inflammatory diseases that might confound the evaluations of benefit from the golimumab therapy Pregnant or lactating females Participants with chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including tuberculosis Participants who had a serious infection (including but not limited to, hepatitis, pneumonia, sepsis, or pyelonephritis), or have been hospitalized for an infection, or have been treated with intravenous (IV) antibiotics for an infection within 2 months prior to first administration of study agent Additional protocol-defined exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1: Placebo then Golimumab<br>Participants will receive intravenous infusions of placebo at Weeks 0, 4 and 12. At Week 16, all participants receiving placebo will begin receiving intravenous infusions of golimumab 2 milligram per kilogram (mg/kg) at Weeks 16, 20 and thereafter every 8 weeks up to Week 52. | Drug: Placebo<br>* Participants will receive matching placebo.<br>Drug: Golimumab<br>* Participants will receive 2mg/kg of intravenous infusions of golimumab .<br>|
| Experimental: Treatment Group 2: Golimumab<br>Participants will receive intravenous infusions of golimumab 2 mg/kg at Weeks 0, 4 and thereafter every 8 weeks up to Week 52. At Week 16, participants will receive a placebo infusion to maintain the blind. | Drug: Placebo<br>* Participants will receive matching placebo.<br>Drug: Golimumab<br>* Participants will receive 2mg/kg of intravenous infusions of golimumab .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved at Least 20 Percent Improvement From Baseline in the Assessment of SpondyloArthritis International Society (ASAS 20) at Week 16 | ASAS 20 defined as 20 percent (%) improvement compared to baseline in the ASAS Working Group criteria: that is, greater than or equal to (>=)20% improvement from baseline in at least 3 of the 4 domains: patient's global assessment of disease activity (0=very well,10 =very poor), total back pain (0=no pain,10=most severe pain), function (self-assessment using BASFI [0=no functional impairment to 10= maximal impairment]), inflammation (0=none,10=very severe) with an absolute improvement of at least 1 (0-10 centimeter (cm) visual analogue scale [VAS]), and an absence of deterioration (defined as >=20% worsening and absolute worsening of at least 1 on a 0-10 cm scale) in the potential remaining domain. | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved at Least 40 Percent Improvement From Baseline in the Assessment of SpondyloArthritis International Society (ASAS 40) at Week 16 | An ASAS 40 response is defined as >=40% improvement from baseline in 3 of 4 domains: patient's global assessment of disease activity (0=very well, 10=very poor), total back pain (0=no pain, 10=most severe pain), function (self-assessment using BASFI (0=no functional impairment to 10=maximal impairment), inflammation (0=none, 10=very severe) with an absolute improvement of at least 2 (0-10 cm VAS), and no deterioration in the remaining domain. | Week 16 | 
| Percentage of Participants Who Achieved at Least 50 Percent Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 16 | The BASDAI is a self-assessment tool to determine disease activity using a VAS of 0-10 cm (0=none and 10=very severe) participant's answered 6 questions measuring fatigue, spinal pain, joint pain, enthesitis, and morning stiffness. The final BASDAI is calculated as a mean of individual questions with a final score range of 0 to 10 cm; 0=best and 10=worst. | Week 16 | 
| Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Score at Week 16 | The BASFI is a participant's self-assessment of physical function represented as a mean of 10 questions, each question rated on VAS 0 to 10 cm (VAS 0 to 10 cm; 0=easy to 10=impossible), 8 of which relate to the participant's functional anatomy and 2 of which relate to a participant's ability to cope with everyday life. | Baseline and Week 16 | 
| Change From Baseline in Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 16 | The Medical Outcome Study health measure SF-36 questionnaire is a well-validated and widely used quality-of-life instrument. It is a self-administered survey that consists of 8 multi-item scales: The 4 subscales of the SF-36 comprises the PCS score (physical functioning, role-physical, bodily pain, and general health) and the 4 subscales of the SF-36 comprises the MCS score (vitality, social functioning, role-emotional, and mental health). PCS and MCS are scored from 0 to 100 with higher scores indicating better health (worst value is 0 and best value is 100), which are scored using a norm-based system where linear transformations are performed to transform scores to a mean of 50 and standard deviation of 10. | Baseline and Week 16 | 
| Change From Baseline in Short Form-36 Health Survey (SF-36) Mental Component Summary (MCS) Score at Week 16 | The Medical Outcome Study health measure SF-36 questionnaire is a well-validated and widely used quality-of-life instrument. It is a self-administered survey that consists of 8 multi-item scales: The 4 subscales of the SF-36 comprises the PCS score (physical functioning, role-physical, bodily pain, and general health) and the 4 subscales of the SF-36 comprises the MCS score(vitality, social functioning, role-emotional, and mental health). PCS and MCS are scored from 0 to 100 with higher scores indicating better health (worst value is 0 and best value is 100), which are scored using a norm-based system where linear transformations are performed to transform scores to a mean of 50 and standard deviation of 10. | Baseline and Week 16 | 
| Percentage of Participants With Low Level of Disease Activity (ASAS Partial Remission) at Week 16 | Low level of disease activity was measured by criteria for ASAS partial remission, defined as a value below 2 on a scale of 0 to 10 cm in each of the 4 ASAS domains: patient's global assessment of disease activity, total back pain, function (BASFI), inflammation. | Week 16 | 
| Change From Baseline in Ankylosing Spondylitis Quality of Life (ASQoL) at Week 16 | The ASQoL is a self-administered health-related quality of life (HRQOL) instrument. It consists of 18 items requesting a Yes or No response to questions related to the impact of the disease/condition (including pain) on sleep, mood, motivation, ability to cope, activities of daily living, independence, relationships, and social life. A score of 1 is given to a response of yes on each item and all item scores are summed to a total score with a range of 0 to 18. Higher scores indicate worse HRQOL. | Baseline and Week 16 | 
| Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Week 16 | BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: tragus to wall distance, lumbar flexion, cervical rotation, lumbar side flexion, and intermalleolar distance. Each measure was scored 0-2 (0=normal mobility/mild disease involvement, 1=moderate disease involvement, 2=severe disease involvement) to give a final total BASMI score ranging from 0 to 10. The higher the BASMI score, the more severe was the participant's limitation of movement due to their AS. | Baseline and Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ankylosing Spondylitis, Golimumab, SIMPONI