A Study of Guselkumab Administered Subcutaneously in Bio-naive Participants With Active Psoriatic Arthritis Axial Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active psoriatic arthritis (PsA) axial disease by assessing reduction in axial symptoms and inflammation.

Detailed Description
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PsA is a chronic inflammatory musculoskeletal disease that has 6 disease domains, and axial disease represents one of the domains. Guselkumab is a fully human immunoglobulin (Ig) G1 lambda monoclonal antibody (mAb) that by binding to the p19 protein subunit of interleukin (IL)-23, blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23-mediated intracellular signaling, activation, and cytokine production. This study will consist of a screening phase (up to 6 weeks), a treatment phase (up to 48 weeks, including a placebo-controlled period from Week 0 to Week 24 and an active-controlled treatment phase from Week 24 to Week 48), and a safety follow-up phase (up to Week 60). The efficacy assessments will include assessment such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score and the safety assessments will include evaluations of physical examinations, vital signs, electrocardiograms, clinical laboratory tests, and adverse events. The overall duration of the study will be up to 14 months.

Official Title
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A Phase 4, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Bio-naive Participants With Active Psoriatic Arthritis Axial Disease

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Drug: Guselkumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of psoriatic arthritis (PsA) for at least 6 months prior to the first administration of study intervention and meet classification criteria for psoriatic arthritis (CASPAR) criteria at screening Have active PsA as defined by: a) at least 3 swollen joints and at least 3 tender joints at screening and at baseline and b) C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram/deciliter (mg/dL) at screening from the central laboratory, and despite previous non-biologic disease modifying antirheumatic drug (DMARD), apremilast, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy Have magnetic resonance imaging (MRI)-confirmed PsA axial disease (positive MRI spine and/or sacroiliac [SI] joints, shown by a Spondyloarthritis Research Consortium of Canada [SPARCC] score of >= 3 in either the spine or the sacroiliac joints) Have a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of at least 4, and have a spinal pain score (on a visual analog scale [VAS]) of at least 4 Have active plaque psoriasis, with at least 1 psoriatic plaque of >= 2 centimeter (cm) diameter and/or nail changes consistent with psoriasis, or documented history of plaque psoriasis Exclusion Criteria: Has known allergies, hypersensitivity, or intolerance to guselkumab or its excipients Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS)/non-radiographic-axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, or Lyme disease Has previously received any biologic treatment Has ever received a Janus kinase (JAK) inhibitor including but not limited to tofacitinib, baricitinib, filgotinib, peficitinib, decernotinib, upadacitinib or any other investigational JAK inhibitor Has received any systemic immunosuppressants (example, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study intervention

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: Group 1: Guselkumab and Placebo<br>Participants will receive guselkumab and matching placebo subcutaneously (SC) to maintain the blind. | Drug: Guselkumab<br>* Guselkumab will be administered as subcutaneous injection.<br>* Other names: TREMFYA;Drug: Placebo<br>* Matching placebo will be administered as subcutaneous injection.<br>|
| Experimental: Group 2: Guselkumab<br>Participants will receive guselkumab SC. | Drug: Guselkumab<br>* Guselkumab will be administered as subcutaneous injection.<br>* Other names: TREMFYA;|
| Experimental: Group 3: Placebo followed by Guselkumab<br>Participants will receive matching placebo and will cross over to receive guselkumab SC. | Drug: Guselkumab<br>* Guselkumab will be administered as subcutaneous injection.<br>* Other names: TREMFYA;Drug: Placebo<br>* Matching placebo will be administered as subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Score at Week 24 | BASDAI is a self-assessment tool that consists of 6 questions relating to 5 major symptoms of ankylosing spondylitis: fatigue, spinal pain, joint pain, enthesitis, qualitative morning stiffness and quantitative morning stiffness. First 5 items were scored on a 10 centimeter (cm) visual analog scale (VAS) ranging from 0 equals to (=) none to 10=very severe. Quantitative morning stiffness was scored on a 10 cm VAS ranging from 0=0 hours to 10=2 or more hours. 2 scores for qualitative and quantitative morning stiffness were averaged, and total BASDAI score was average of the 5 scores of each symptom, ranging from 0 (none) to 10 (very severe). Higher scores indicate greater disease severity. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (ASDAS-CRP) at Week 24 | The ASDAS-CRP is a composite of 5 disease activity variables with only partial overlap. The 4 self-reported items included in this index are back pain (VAS), duration of morning stiffness, peripheral pain/swelling, and participant global assessment of disease activity; these are combined with the C-reactive protein (CRP) value. Selected cut-offs for improvement scores are: a change greater than or equal to (>=) 1.1 units for clinically important improvement and a change >= 2.0 units for major improvement. | Baseline and Week 24 | 
| Change from Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) at Week 24 | DAPSA assessed the joint domain of psoriatic arthritis (PsA) and was derived from the sum of the following components: tender joint count (0-68), swollen joint count (0-66), CRP level (milligram/deciliter [mg/dL], value less than [<] lower limit of quantification [LLOQ] is considered equal to half of the value of LLOQ for numerical calculations), participant assessment of pain (0-10 cm VAS, 0=no pain, 10=worst possible pain), and participant's global assessment of disease activity on arthritis (0 to 10 cm VAS, 0=excellent and 10=poor). A higher score indicates more active disease activity. Negative changes from baseline indicate improvement of PsA disease activity. The assessment does not have a score range with an upper or lower bound. | Baseline and Week 24 | 
| Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 24 | HAQ-DI score assess functional status of participant. It is 20 question instrument that assess degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0=indicating no difficulty, to 3=indicating inability to perform a task in that area. Total HAQ score is average of the computed categories scores ranging from 0-3 where 0=least difficulty and 3=extreme difficulty. Lower scores are indicative of better functioning. Negative change from baseline indicates improvement of physical function. | Baseline and Week 24 | 
| Percentage of Participants with Investigator's Global Assessment (IGA) 0/1 Response at Week 24 among Participants with >= 3% Body Surface Area (BSA) Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline | Percentage of participants with IGA 0/1 response at week 24 among the participants with >= 3 percent (%) BSA psoriatic involvement and an IGA score of >= 2 (mild) at baseline will be reported. The IGA documents the investigator's assessment of the participants psoriasis at a given timepoint. Overall lesions are graded for induration, erythema, and scaling using 0 (no evidence), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe) scale. The IGA score of psoriasis is based upon the average of induration, erythema and scaling scores. The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). | Week 24 | 
| Change from Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Score for Magnetic Resonance Imaging (MRI) Sacroiliac (SI) Joints at Week 24 | Change from baseline in SPARCC score for MRI SI joints at week 24 among the participants with a positive MRI of the sacroiliac joints at baseline will be reported. SPARCC method focuses on the cartilaginous portion of the SI joint, and scores presence (score of 1) versus absence (score of 0) of bone marrow edema in each SI joint quadrant. | Baseline and Week 24 | 
| Percentage of Participants who Achieve a >= 50 % Improvement from Baseline in BASDAI Score at Week 24 | Percentage of participants who achieve a >= 50 % improvement from baseline in BASDAI score at week 24 will be reported. | Baseline and Week 24 | 
| Percentage of Participants who Achieve ASDAS Clinically Important Improvement at Week 24 | Percentage of participants who achieve ASDAS clinically important improvement at week 24 will be reported. | Week 24 | 
| Percentage of Participants who Achieve Ankylosing Spondylitis Activity Score (ASAS) 40 Response at Week 24 | Percentage of participants who achieve ASAS 40 response at Week 24 will be reported. ASAS 40 defined as improvement from baseline of >= 40% and with an absolute improvement from baseline of at least 2 on 0 to 10 cm scale in at least 3 of following 4 domains: Participant's global assessment (0 to 10 cm; 0=very well, 10=very poor), total back pain (0 to 10 cm; 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 10 cm; 0=none, 10=very severe); no worsening at all from baseline in remaining domain. | Week 24 | 
| Percentage of Participants who Achieve ASDAS Major Improvement at Week 24 | Percentage of participants who achieve ASDAS major improvement at Week 24 will be reported. | Week 24 | 
| Change from Baseline in SPARCC Score for MRI Spine at Week 24 | Change from baseline in SPARCC score for MRI spine at week 24 among the participants with a positive MRI of the spine at baseline will be reported. The SPARCC scoring system for the spine scores the 6 discovertebral units considered by the reader as the most abnormal, and then separately assesses each quadrant of 3 adjacent sagittal slices, with additional points for depth and high intensity of the lesion. | Baseline and Week 24 | 
| Number of Participants with Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to 60 weeks | 
| Number of Participants with Serious Adverse Events (SAEs) | A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important. | Up to 60 weeks | 
| Number of Participants with Reasonably Related AEs | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to 60 weeks | 
| Number of Participants with AEs Leading to Discontinuation of Study Intervention | Number of participants with AEs leading to discontinuation of study intervention will be reported. | Up to 60 weeks | 
| Number of Participants with Infections | Number of participants with infections will be reported. | Up to 60 weeks | 
| Number of participants with Injection-Site Reactions | Number of participants with injection-site reactions will be reported. A study intervention injection-site reaction is any adverse reaction at a subcutaneous study intervention injection-site. | Up to 60 weeks | 
| Number of Participants with Laboratory Abnormalities (Chemistry, Hematology) by Maximum Toxicity (Common Terminology Criteria for Adverse Events [CTCAE 5.0]) Grades | Number of participants with laboratory abnormalities (chemistry, hematology) by maximum toxicity (CTCAE 5.0) grades will be reported. Grade refers to the severity of the AE as follows: Grade 1- Mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2- Moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental Activities of Daily Living (ADL); Grade 3- Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self-care ADL; Grade 4- Life-threatening consequences, urgent intervention indicated; Grade 5- Death related to AE. | Up to 60 weeks | 
| Serum Guselkumab Concentration Over Time | Serum guselkumab concentration over time will be reported. | Up to 60 weeks | 
| Number of Participants with Antibodies to Guselkumab | Number of participants with antibodies to guselkumab will be reported. | Up to 60 weeks |