Effect of Golimumab in Participants With Active Axial Spondyloarthritis (P07642, MK-8259-006)

Study Overview
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Brief Summary
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This two-part study was to evaluate the effect of golimumab (SCH 900259, MK-8259) in participants with active axial spondyloarthritis (axial SpA). In Part 1, participants were to receive golimumab 50 mg or matching placebo subcutaneous injections on Day 1 (Baseline) and at Weeks 4, 8, and 12. During Part 1 of the study, participants were to not know the identity of the injection. In the Part 2 extension, all participants were to receive golimumab 50 mg subcutaneous injections beginning on Week 16 and then every 4 weeks up to Week 48. In Part 2, the participants were to be told they were receiving active study drug. The primary hypothesis of this study was that treatment with golimumab 50 mg every 4 weeks is superior to placebo as measured by the proportion of participants achieving an Assessment in Ankylosing Spondylitis (ASAS) 20 response at Week 16.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Effect of Golimumab Administered Subcutaneously in Subjects With Active Axial Spondyloarthritis (Protocol No. P07642, Also Known as MK-8259-006-02).

Conditions
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Spondylitis, Ankylosing

Intervention / Treatment
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* Biological: Golimumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active axial spondyloarthritis with disease duration ≤5 years, and chronic back pain of ≥3 month duration Have either an inadequate response to 30 days of optimal daily doses of at least one non-steroidal anti-inflammatory drug (NSAID) or must be unable to receive a full 30 day maximal NSAID therapy because of intolerance, toxicity or contraindications to NSAIDs Females of child-bearing potential must use contraception No history of untreated latent or active tuberculosis Exclusion Criteria: Fulfillment of modified New York criteria for ankylosing spondylitis Has ever received tumor necrosis factor (TNF)-α targeted therapy or any biological agents Any systemic inflammatory condition other than spondyloarthritis Serious infection within 2 months Any known malignancy or a history of malignancy within the previous 5 years Has or had a substance abuse (drug or alcohol) problem within the previous 2 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Golimumab→Golimumab<br>In Part 1, participants receive golimumab 50 mg, administered subcutaneously (SC) every 4 weeks for up to 12 weeks (16 weeks of treatment). In Part 2, participants receive golimumab 50 mg, administered SC every 4 weeks for up to 28 weeks (32 weeks of treatment). (Combined total of up to 48 weeks treatment with golimumab.) | Biological: Golimumab<br>* Golimumab 50 mg SC injection every 4 weeks<br>|
| Placebo Comparator: Placebo→Golimumab<br>In Part 1, participants receive placebo, administered SC every 4 weeks for up to 12 weeks (16 weeks of treatment). In Part 2, participants receive golimumab 50 mg, administered SC every 4 weeks for up to 28 weeks (32 weeks of treatment). (Combined total of up to 32 weeks treatment with golimumab.) | Biological: Golimumab<br>* Golimumab 50 mg SC injection every 4 weeks<br>Biological: Placebo<br>* Placebo SC injection every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Assessment in Ankylosing Spondylitis (ASAS) 20 Response at Week 16 | The ASAS consists of 4 domains: participant global assessment, total back pain, function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and inflammation (mean of questions 5 and 6 of Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Each domain is measured on a 100-mm visual analog scale (VAS) from 0 mm=the very best situation to 100 mm=the very worst situation, with a higher score indicating more severe impairment. ASAS 20 is a 20% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of >=20% from Baseline and an absolute improvement from Baseline of >=10 mm in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a >=20% worsening and an absolute worsening of >=10 mm) in the potential remaining domain. The percentages of participants who achieved ASAS 20 were calculated. | Week 16 | 
| Percentage of Participants Who Experienced at Least One Adverse Event (AE) | An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. The percentages of participants who experienced at least one AE were calculated for each part of the study. | Up to 16 weeks for Part 1: Week 16 through up to 60 weeks for Part 2 (Up to 12 weeks after last dose of study drug) | 
| Percentage of Participants Who Discontinued Study Drug Due to an AE | An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug, whether or not considered related to the study drug. The percentages of participants who discontinued study drug due to an AE were calculated for each part of the study. Participants may have discontinued study drug without discontinuing from the study. | Up to 16 weeks for Part 1; Week 16 through up to 48 weeks for Part 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving an Assessment in Ankylosing Spondylitis (ASAS) 40 Response at Week 16 | The ASAS consists of 4 domains: participant global assessment, total back pain, function (BASFI), and inflammation (mean of questions 5 and 6 of BASDAI). Each domain is measured on a 100-mm VAS from 0 mm=the very best situation to 100 mm=the very worst situation, with a higher score indicating more severe impairment. ASAS 40 is a 40% improvement in response (per the Assessment in Ankylosing Spondylitis International Working Group) defined as meeting 2 criteria: 1) An improvement of >=40% from Baseline and an absolute improvement from Baseline of >=20 mm in at least 3 of 4 domains, and 2) Absence of deterioration from Baseline (defined as a >=0% worsening and an absolute worsening of >=0 mm) in the potential remaining domain. The percentages of participants who achieved ASAS 40 were calculated. | Week 16 | 
| Percentage of Participants Achieving Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 at Week 16 | The BASDAI is a summary of 6 participant-assessed 100-mm VAS for a) Fatigue, b) Spinal pain (overall), c) Peripheral arthritis, d) Enthesitis, e) Qualitative morning stiffness (intensity) and f) Quantitative morning stiffness (duration). Each VAS is measured as 0=none to 100=very severe, with a higher score indicating more severe symptoms. The BASDAI score is calculated as 0.2 time (a+b+c+d+[0.5 times e+f]) and can range from 0 to 100. The BASDAI 50 is defined as improvement by at least 50% from Baseline in the BASDAI score. The percentages of participants who achieved BASDAI 50 were calculated. | Week 16 | 
| Percentage of Participants Achieving ASAS Partial Remission at Week 16 | ASAS partial remission was defined as a VAS score of less than 20 mm in each of the 4 domains of ASAS 20: participant global assessment, pain (total back pain), function and inflammation. The percentages of participants who achieved ASAS partial remission were calculated. | Week 16 | 
| Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Sacroiliac (SI) Joints Score at Week 16 | Participants underwent MRI of the SI joints, without contrast, at Screening and Week 16 to assess the presence or absence of active inflammation of the SI joints. Scoring was based on 6 consecutive MRI slices through the SI joint. Each slice was divided into 4 quadrants. Each of the 48 quadrants was scored with respect to the presence of inflammation (0=no, 1=yes), yielding a maximum score of 48. Each slice was also assessed for the presence of a lesion exhibiting either intense signal or a depth >=1 cm anywhere within the SI joint of the 6 slices (0=no, 1=yes), yielding a maximum score of 24. Total SI joint scores could range from 0 to 72, with a higher score indicating more signs of disease. | Baseline and Week 16 |