Back to resultsA Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory Participants With Active Radiographic Axial Spondyloarthritis
Primary Purpose
Axial Spondyloarthritis
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Placebo
Ustekinumab 45 mg
Ustekinumab 90 mg
Golimumab 50 mg
Sponsored by
About this trial
This is an interventional treatment trial for Axial Spondyloarthritis focused on measuring Ankylosing Spondylitis, Ustekinumab, Golimumab, STELARA
Eligibility Criteria
Inclusion Criteria:
- Participants must have a diagnosis of definite ankylosing spondylitis (AS), as defined by the modified 1984 New York criteria. The radiographic criterion must be confirmed by a central xray reader and at least 1 clinical criterion must be met
- Participants must have symptoms of active disease at screening and at baseline, as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of greater than or equal to (>=4) and a visual analog scale (VAS) score for total back pain of >=4, each on a scale of 0 to 10
- Participants with elevated high sensitivity C-reactive protein (hsCRP) level of >=0.300 milligram per deciliter (mg/dL) at screening
- Refractory by either lack of benefit or documented intolerance to 1 and no more than 1 anti-TNF(alpha) agent
- Inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over a 4-week period in total with maximal doses of NSAID(s), or is unable to receive a full 4 weeks of maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs.
- Participants with complete ankylosis of the spine are permitted to be included in the study, but will be limited to approximately 10 percent (%) of the study population
Exclusion Criteria:
- Participants who have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy, including but not limited to, rheumatoid arthritis, systemic lupus erythematosus, or Lyme disease
- Participants who have received infliximab or infliximab biosimilar, within 12 weeks of the first study agent administration; have received adalimumab, adalimumab biosimilar, or certolizumab pegol within 6 weeks of the first study agent administration; have received etanercept or etanercept biosimilar within 6 weeks of the first study agent administration
- Participants who have ever received golimumab
- Participants who are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 5 months after receiving the last administration of study agent
- Participants who have received any systemic immunosuppressives or disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent. Medications in these categories include, but are not limited to leflunomide, chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Group 1 (placebo)
Group 2 (ustekinumab 45 mg)
Group 3 (ustekinumab 90 mg)
Arm Description
Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 24 all participants (with the exception of participants who qualified for early escape [EE]) will be re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 52. Participants who meet EE criteria (less than [<] 10 percent [%] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52.
Ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.
Ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.
Outcomes
Primary Outcome Measures
Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 24
ASAS 40 defined as improvement from baseline of greater than or equal to (>=) 40% and with an absolute improvement from baseline of at least 2 on 0 to10cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI(self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI(non responder imputation)] (missing responses at post baseline visit imputed as non-responder).
Secondary Outcome Measures
Percentage of Participants Who Achieved an ASAS 20 Response at Week 24
ASAS 20 defined as improvement from baseline of >= 20% from baseline and with an absolute improvement from baseline of 1 on a 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); absence of deterioration (>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in the potential remaining domain. ASAS20 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Percentage of Participants Who Achieved at Least a 50 Percent (%) Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24
BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), morning stiffness(MS) (2 questions: duration and severity). Each question is an easy to answer 10 cm visual analog scale (VAS), with 0 being none, and 10 being very severe and for the last question related to MS duration: 0(0 hours), 10(2 or more hours). In order to give each of 5 symptoms equal weight, mean of 2 questions about MS will be added to total of remaining 4 scores, final BASDAI score (ranging 0-10) is average of overall total score. Higher BASDAI score indicates more severe AS symptom. 50% improvement in response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 24
The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Missing data were imputed using early escape rule (consider non-responder at Week 20 and 24).
Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score-C Reactive Protein (ASDAS-CRP) Inactive Disease (<1.3) at Week 24
ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale [NRS]) included are total back pain (TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment (PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121*total back pain) + (0.110*participant global) + (0.073*peripheral pain/swelling) + (0.058* duration of morning stiffness) + (0.579*Ln(CRP+1). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =>2 hours). Inactive disease is defined as an ASDAS score <1.3. ASDAS (CRP) Inactive Disease is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responder).
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24
Change from baseline in hsCRP was reported. hsCRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing).
Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20
ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale [NRS]) included are total back pain (TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment (PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121*total back pain) + (0.110*participant global) + (0.073*peripheral pain/swelling) + (0.058* duration of morning stiffness) + (0.579*Ln(CRP+1)). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =>2 hours). Inactive disease is defined as an ASDAS score <1.3. ASDAS (CRP) Inactive Disease is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non- responders).
Percentage of Participants Who Achieved ASAS 40 Responses at Week 4, 8, 12, 16 and 20
ASAS 40 defined as improvement from baseline >= 40% and with an absolute improvement from baseline of at least 2 on 0 to10cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Percentage of Participants Who Achieved ASAS 20 Responses at Week 4, 8, 12, 16 and 20
ASAS 20 defined as improvement from baseline of >= 20% and with an absolute improvement from baseline of 1 on a 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); absence of deterioration (>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in the potential remaining domain. ASAS20 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20
BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), morning stiffness(MS) (2 questions: duration and severity). Each question is an easy to answer 10 cm visual analog scale (VAS), with 0 being none, and 10 being very severe and for the last question related to MS duration: 0(0 hours), 10(2 or more hours). In order to give each of 5 symptoms equal weight, mean of 2 questions about MS will be added to total of remaining 4 scores, final BASDAI score (ranging 0-10) is average of overall total score. Higher BASDAI score indicates more severe AS symptom. 50% improvement in response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Change From Baseline in BASFI Total Score at Week 4, 8, 12, 16 and 20
The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Missing data were imputed using early escape rule (consider non-responder at Week 20 and 24).
Full Information
NCT ID
NCT02438787
First Posted
May 6, 2015
Last Updated
August 26, 2019
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT02438787
Brief Title
A Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory Participants With Active Radiographic Axial Spondyloarthritis
Official Title
A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory Subjects With Active Radiographic Axial Spondyloarthritis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
This study was stopped because ustekinumab did not achieve key endpoints in a related study. The safety profile was consistent with past ustekinumab studies.
Study Start Date
July 31, 2015 (Actual)
Primary Completion Date
August 31, 2017 (Actual)
Study Completion Date
August 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to assess the efficacy of ustekinumab, in adult anti-TNF(alpha) refractory participants with active radiographic axial spondyloarthritis (AxSpA), as measured by the reduction in signs and symptoms of radiographic AxSpA.
Detailed Description
This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study medication assigned to participants 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. The study consists of 3 phases; Screening (up to 8 weeks), Treatment phase: placebo-controlled (Week 0 to 24) and active treatment (Week 24 to Week 52), and Safety Follow-up (up to 12 weeks). Participants will be randomly assigned to 1 of 3 treatment groups: placebo, ustekinumab 45 mg and ustekinumab 90 mg. The total duration of study will be up to 64 weeks. Participants will be primarily assessed for Assessment of SpondyloArthritis International Society (ASAS) 40 response at Week 24. Participants' safety will be monitored throughout the trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Axial Spondyloarthritis
Keywords
Ankylosing Spondylitis, Ustekinumab, Golimumab, STELARA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
315 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1 (placebo)
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16. At Week 24 all participants (with the exception of participants who qualified for early escape [EE]) will be re-randomized to receive either ustekinumab 45 or 90 milligram (mg) SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 52. Participants who meet EE criteria (less than [<] 10 percent [%] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52.
Arm Title
Group 2 (ustekinumab 45 mg)
Arm Type
Experimental
Arm Description
Ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.
Arm Title
Group 3 (ustekinumab 90 mg)
Arm Type
Experimental
Arm Description
Ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52. At Week 24, participants will receive placebo SC injection to maintain the blind. Participants who meet EE criteria (<10% improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and q4w thereafter through Week 52.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo subcutaneous (SC) injection at Weeks 0, 4, and 16 in Group 1.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab 45 mg
Intervention Description
Ustekinumab 45 mg SC injection at Weeks 24 and 28 followed by every 12 weeks (q12w) dosing, with the last administration of study agent at Week 52 in Group 1. Participants will start with ustekinumab 45 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52 in Group 2.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab 90 mg
Intervention Description
Ustekinumab 90 mg SC injection at Weeks 24 and 28 followed by q12w dosing, with the last administration of study agent at Week 52 in Group 1. Participants will start with ustekinumab 90 mg SC injection at Weeks 0 and 4, followed by q12w dosing, with the last administration of study agent at Week 52 in Group 3.
Intervention Type
Drug
Intervention Name(s)
Golimumab 50 mg
Intervention Description
Participants who meet EE criteria (less than [<] 10 percent [%] improvement from baseline in both total back pain and morning stiffness measures at both Week 12 and Week 16) will be administered open-label golimumab 50 mg SC administrations at Week 16 and every 4 weeks (q4w) thereafter through Week 52 in Group 1, 2 and 3.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved an Assessment of SpondyloArthritis International Society (ASAS) 40 Response at Week 24
Description
ASAS 40 defined as improvement from baseline of greater than or equal to (>=) 40% and with an absolute improvement from baseline of at least 2 on 0 to10cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI(self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI(non responder imputation)] (missing responses at post baseline visit imputed as non-responder).
Time Frame
Week(W) 24
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieved an ASAS 20 Response at Week 24
Description
ASAS 20 defined as improvement from baseline of >= 20% from baseline and with an absolute improvement from baseline of 1 on a 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); absence of deterioration (>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in the potential remaining domain. ASAS20 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Time Frame
Week 24
Title
Percentage of Participants Who Achieved at Least a 50 Percent (%) Improvement From Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24
Description
BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), morning stiffness(MS) (2 questions: duration and severity). Each question is an easy to answer 10 cm visual analog scale (VAS), with 0 being none, and 10 being very severe and for the last question related to MS duration: 0(0 hours), 10(2 or more hours). In order to give each of 5 symptoms equal weight, mean of 2 questions about MS will be added to total of remaining 4 scores, final BASDAI score (ranging 0-10) is average of overall total score. Higher BASDAI score indicates more severe AS symptom. 50% improvement in response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Time Frame
Week 24
Title
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) Total Score at Week 24
Description
The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Missing data were imputed using early escape rule (consider non-responder at Week 20 and 24).
Time Frame
Baseline and Week 24
Title
Percentage of Participants Who Achieved Ankylosing Spondylitis Disease Activity Score-C Reactive Protein (ASDAS-CRP) Inactive Disease (<1.3) at Week 24
Description
ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale [NRS]) included are total back pain (TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment (PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121*total back pain) + (0.110*participant global) + (0.073*peripheral pain/swelling) + (0.058* duration of morning stiffness) + (0.579*Ln(CRP+1). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =>2 hours). Inactive disease is defined as an ASDAS score <1.3. ASDAS (CRP) Inactive Disease is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non-responder).
Time Frame
Week 24
Title
Change From Baseline in High Sensitivity C-Reactive Protein (hsCRP) Levels Through Week 24
Description
Change from baseline in hsCRP was reported. hsCRP is a sensitive laboratory assay for serum levels of C-Reactive Protein, which is a biomarker of inflammation. Early escape rule was applied (measurement value at Week 20 and Week 24 was set as missing).
Time Frame
Baseline, Week 4, 8, 12, 16, 20 and 24
Title
Percentage of Participants With ASDAS (CRP) Inactive Disease (<1.3) at Week 4, 8, 12, 16 and 20
Description
ASDAS includes CRP mg/L; four additional self-reported items (rated on 0-10cm VAS or 0-10 numerical rating scale [NRS]) included are total back pain (TBP), duration of morning stiffness (DMS), peripheral pain/swelling and patient global assessment (PGA). ASDAS scores calculated as: ASDAS(CRP) = (0.121*total back pain) + (0.110*participant global) + (0.073*peripheral pain/swelling) + (0.058* duration of morning stiffness) + (0.579*Ln(CRP+1)). The disease activity, TBP, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe) and DMS on a numeric rating scale (0 to 10, with 0 being none and 10 representing a duration of =>2 hours). Inactive disease is defined as an ASDAS score <1.3. ASDAS (CRP) Inactive Disease is based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24), NRI(missing responses at post baseline visit imputed as non- responders).
Time Frame
Week 4, 8, 12, 16 and 20
Title
Percentage of Participants Who Achieved ASAS 40 Responses at Week 4, 8, 12, 16 and 20
Description
ASAS 40 defined as improvement from baseline >= 40% and with an absolute improvement from baseline of at least 2 on 0 to10cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); no worsening at all from baseline in remaining domain. ASAS40 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Time Frame
Week 4, 8, 12, 16 and 20
Title
Percentage of Participants Who Achieved ASAS 20 Responses at Week 4, 8, 12, 16 and 20
Description
ASAS 20 defined as improvement from baseline of >= 20% and with an absolute improvement from baseline of 1 on a 0 to 10 cm scale in at least 3 of following 4 domains: Patient's global assessment (0 to 10cm; 0=very well,10=very poor),total back pain (0 to 10cm; 0=no pain,10=most severe pain), BASFI (self-assessment represented as mean (0 to 10 cm; 0=easy to 10=impossible) of 10 questions, 8 of which relate to participant's functional anatomy and 2 relate to participant's ability to cope with everyday life), Inflammation (0 to 10cm;0=none,10=very severe); absence of deterioration (>= 20% and worsening of at least 1 on a 0 to 10 cm scale) from baseline in the potential remaining domain. ASAS20 response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Time Frame
Week 4, 8, 12, 16 and 20
Title
Percentage of Participants Who Achieved at Least a 50% Improvement From Baseline in BASDAI at Week 4, 8, 12, 16 and 20
Description
BASDAI is used to measure the ankylosing spondylitis (AS) disease severity. It consists of 6 questions: fatigue, spinal pain, arthralgia (joint pain) or swelling, enthesitis (inflammation of tendons and ligaments), morning stiffness(MS) (2 questions: duration and severity). Each question is an easy to answer 10 cm visual analog scale (VAS), with 0 being none, and 10 being very severe and for the last question related to MS duration: 0(0 hours), 10(2 or more hours). In order to give each of 5 symptoms equal weight, mean of 2 questions about MS will be added to total of remaining 4 scores, final BASDAI score (ranging 0-10) is average of overall total score. Higher BASDAI score indicates more severe AS symptom. 50% improvement in response based on imputed data using treatment failure(consider non-responders at and after treatment failure),early escape rules(consider non-responder at Week 20 and 24),non-responder[NRI] (missing responses at post baseline visit imputed as non-responder).
Time Frame
Week 4, 8, 12, 16 and 20
Title
Change From Baseline in BASFI Total Score at Week 4, 8, 12, 16 and 20
Description
The BASFI is composed with 10 questions (each question is answered with a visual analogue scale 0-10 cm) to assess the disease severity, including the first 8 questions regarding to functional anatomy related activities and the remaining 2 questions related to daily activities of AS participants. Each question is a 10cm VAS with a value between 0 (easy) and 10 (impossible). The final BASFI score is the mean of the 10 scores. The BASFI score is the average of the 10 responses and has a possible minimum value of 0 and a possible maximum value of 10. Higher BASFI score indicates more severe functional limitations of the participant due to AS. Missing data were imputed using early escape rule (consider non-responder at Week 20 and 24).
Time Frame
Baseline, Week 4, 8, 12, 16 and 20
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants must have a diagnosis of definite ankylosing spondylitis (AS), as defined by the modified 1984 New York criteria. The radiographic criterion must be confirmed by a central xray reader and at least 1 clinical criterion must be met
Participants must have symptoms of active disease at screening and at baseline, as evidenced by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of greater than or equal to (>=4) and a visual analog scale (VAS) score for total back pain of >=4, each on a scale of 0 to 10
Participants with elevated high sensitivity C-reactive protein (hsCRP) level of >=0.300 milligram per deciliter (mg/dL) at screening
Refractory by either lack of benefit or documented intolerance to 1 and no more than 1 anti-TNF(alpha) agent
Inadequate response to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs) over a 4-week period in total with maximal doses of NSAID(s), or is unable to receive a full 4 weeks of maximal NSAID therapy because of intolerance, toxicity, or contraindications to NSAIDs.
Participants with complete ankylosis of the spine are permitted to be included in the study, but will be limited to approximately 10 percent (%) of the study population
Exclusion Criteria:
Participants who have other inflammatory diseases that might confound the evaluations of benefit from the ustekinumab therapy, including but not limited to, rheumatoid arthritis, systemic lupus erythematosus, or Lyme disease
Participants who have received infliximab or infliximab biosimilar, within 12 weeks of the first study agent administration; have received adalimumab, adalimumab biosimilar, or certolizumab pegol within 6 weeks of the first study agent administration; have received etanercept or etanercept biosimilar within 6 weeks of the first study agent administration
Participants who have ever received golimumab
Participants who are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 5 months after receiving the last administration of study agent
Participants who have received any systemic immunosuppressives or disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX), sulfasalazine (SSZ), or hydroxychloroquine (HCQ) within 4 weeks prior to first administration of study agent. Medications in these categories include, but are not limited to leflunomide, chloroquine, azathioprine, cyclosporine, mycophenolate mofetil, gold, and penicillamine
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Glendale
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Arizona
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United States
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Peoria
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Arizona
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United States
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Phoenix
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Arizona
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United States
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Fremont
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California
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United States
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Saint Petersburg
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United States
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Tampa
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Meridian
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United States
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Chicago
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Monroe
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Eagan
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Orchard Park
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Portland
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Duncansville
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United States
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Wyomissing
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Jackson
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Mesquite
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United States
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Seattle
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Argentina
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Belgium
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Prague 5
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Praha 4
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Uherske Hradiste
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Zlin
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Chambray Les Tours
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France
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Echirolles
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France
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France
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Omsk
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Pyatigorsk
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Saratov
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St.Petersburg
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Ufa
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Zelenograd
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A Coruna
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Spain
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Barcelona
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Spain
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Bilbao
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Spain
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Córdoba
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Spain
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L´Hospitalet de Llobregat
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Spain
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Madrid
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Spain
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Málaga
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Spain
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Sabadell
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Spain
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Santiago de Compostela
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Spain
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Sevilla
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Spain
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Valencia
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Spain
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Changhua
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Taiwan
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Hualien
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Taiwan
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Kaohsiung
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Taichung
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Tainan
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Cherkasy
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Ivano-Frankivsk
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Ukraine
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Lviv
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Ukraine
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Odessa
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Ukraine
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Poltava
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Ternopil
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Ukraine
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Uzhgorod
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Ukraine
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Vinnytsya
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Ukraine
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Zaporizhzhya
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Ukraine
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Bath
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United Kingdom
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Leytonstone
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United Kingdom
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London
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United Kingdom
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Peterborough
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United Kingdom
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Stoke on Trent
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United Kingdom
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Upton
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United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
30225992
Citation
Deodhar A, Gensler LS, Sieper J, Clark M, Calderon C, Wang Y, Zhou Y, Leu JH, Campbell K, Sweet K, Harrison DD, Hsia EC, van der Heijde D. Three Multicenter, Randomized, Double-Blind, Placebo-Controlled Studies Evaluating the Efficacy and Safety of Ustekinumab in Axial Spondyloarthritis. Arthritis Rheumatol. 2019 Feb;71(2):258-270. doi: 10.1002/art.40728. Epub 2018 Dec 29.
Results Reference
derived
Learn more about this trial
A Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Anti-TNF(Alpha) Refractory Participants With Active Radiographic Axial Spondyloarthritis
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