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Efficacy and Safety Study of Guselkumab in the Treatment of Participants With Active Psoriatic Arthritis (PsA)

Primary Purpose

Psoriatic Arthritis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Guselkumab

Ustekinumab

Placebo

About this trial

This is an interventional treatment trial for Psoriatic Arthritis focused on measuring Psoriatic Arthritis, Guselkumab, Ustekinumab, Placebo

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Has had Psoriatic Arthritis (PsA) for at least 6 months before the first administration of study drug and meet classification criteria for Psoriatic Arthritis (CASPAR) at Screening
Had active PsA as defined by:
1. At least 3 swollen joints and at least 3 tender joints at Screening and at baseline
2. C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram (mg)/deciliter (dL) at Screening from the central laboratory
Has at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis
Has plaque psoriasis with body surface area (BSA) involvement greater than or equal to (>=) 3% at Screening and baseline
Has active PsA despite current or previous non-biologic disease-modifying antirheumatic drugs (DMARD), oral corticosteroid, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy
If using methotrexate (MTX), oral corticosteroids or NSAIDs, the dose must be stable

Exclusion Criteria:

Have other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus, or Lyme disease
Has previously received guselkumab or ustekinumab
Has received more than 1 type of biologic anti-tumor necrosis factor (TNF) agent previously
Have received infliximab (or its biosimilars) or golimumab intraveneous (IV) within 12 weeks before the first administration of study drug
Have received adalimumab (or its biosimilars), golimumab subcutaneous (SC), certolizumab pegol or etanercept (or its biosimilars) within 8 weeks before the first administration of study drug

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Guselkumab

Placebo

Arm Description

Participants will receive guselkumab 100 milligram (mg) subcutaneous injection (injected under the skin by way of a needle) at Weeks 0, 4, 12, 20, 28, 36, and 44, and placebo for guselkumab at Week 24 to maintain the blind. Participants who enter early escape at Week 16 will switch to open label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.

Participants will receive placebo for guselkumab at Weeks 0, 4, 12, and 20, and guselkumab 100 mg subcutaneous injection at Weeks 24, 28, 36, and 44. Participants who enter early escape at Week 16 will switch to open label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24

ACR 20 response: at least 20% improvement from baseline in both swollen joint (66 joints) and tender joint (68 joints) counts and at least 20% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (VAS: 0-100 millimeter [mm], 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS:0-100mm, 0=excellent and 100=poor), physician's global assessment of disease activity (VAS:0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0=no difficulty, to 3=inability to perform a task in that area) and serum CRP. Treatment Failure (TF) criteria: Discontinued study drug due to lack of efficacy or worsening of PsA, initiated or increased dose of methotrexate or oral corticosteroids, or initiated prohibited PsA treatments. FAS is full analysis set.

Secondary Outcome Measures

Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI)-75 Response at Week 24

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72 (worst condition). PASI 75 response was defined as at least a 75% reduction in PASI relative to Baseline. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24

Change from baseline in HAQ-DI score is a measure of the change in the physical function, where a negative change reflects an improvement and a positive change reflects worsening of physical function. HAQ-DI is a 20-question instrument that assesses the 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 are scored from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning.

Percentage of Participants Who Achieved an ACR 20 Response at Week 16

ACR 20 response is defined as at least 20 percent (%) improvement from baseline in both swollen joint (66 joints) and tender joint (68 joints) counts and at least 20% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (visual analog scale [VAS]: 0-100 millimeter [mm]; 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS: 0-100 mm, 0=excellent and 100=poor), physician's global assessment of disease activity (VAS: 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).

Percentage of Participants Who an Achieved ACR 50 Response at Week 24

ACR 50 response is defined as at least 50 % improvement from baseline in both swollen joint (66 joints) and tender joint (68 joints) counts and at least 50% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (VAS:0-100 mm; 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS:0-100mm; 0=excellent and 100=poor), physician's global assessment of disease activity (VAS: 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum CRP.

Percent Change From Baseline in Leeds Enthesitis Index (LEI) Scores Among Participants With Enthesitis at Week 24

Enthesitis was assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with psoriatic arthritis (PsA), and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Percent Change From Baseline in Dactylitis Scores Among Participants With Dactylitis at Baseline at Week 24

Dactylitis is characterized by swelling of the entire finger or toe. The severity of dactylitis is scored on a scale of 0-3, where 0, 1, 2, 3 indicates none, mild, moderate, severe, respectively in each digit of the hands and feet. The range of total dactylitis scores for a participant is 0-60. Higher score indicates more severe dactylitis.

Percentage of Participants Who Achieved ACR 20, ACR 50, and ACR 70 Responses at Weeks 4, 8, 12, 16, 20, and 24

ACR 20, 50, and 70 response is defined as at least 20%, 50%, and 70% improvement from baseline in swollen joint (66 joints) and tender joint (68 joints) counts and at least 20%, 50%, and 70% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (VAS: 0-100mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS: 0-100mm; 0=excellent and 100=poor), physician's global assessment of disease activity (VAS: 0-100mm; 0=no arthritis activity and 100= extremely active arthritis), patient's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP).

Percentage of Participants Who Achieved ACR 20, ACR 50, and ACR 70 Responses at Weeks 24, 28, 32, 36, 44, and 56

ACR 20, ACR 50 and ACR 70 response is defined as at least 20%, 50%, and 70% improvement from baseline in swollen joint (66 joints) and tender joint (68 joints) counts and at least 20%, 50%, and 70% improvement from baseline in 3 of following 5 assessments: patient's assessment of pain (VAS: 0-100mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity on arthritis (VAS: 0-100mm; 0=excellent and 100=poor), physician's global assessment of disease activity (VAS; 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas;derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum C-Reactive Protein (CRP). As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Percent Change From Baseline in the ACR Components at Weeks 12 and 24

The 7 components of ACR response are: swollen joint counts (0-66), tender joint counts (0-68), patient's assessment of pain (PAIN) (VAS:0-100mm; 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (GDPT) on arthritis (VAS:0-100mm; 0=excellent and 100= poor), physician's global assessment of disease activity (GDEV) (VAS: 0-100mm; 0=no arthritis activity and 100 = extremely active arthritis), patient's assessment of physical function measured by HAQ-DI (20-question instrument assessing 8 functional areas (total score of 0-24 with lower score indicating better functioning);derived HAQ-DI ranges from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area) and serum CRP.

Percent Change From Baseline in the ACR Components at Weeks 24, 28, 32, 36, 44 and 56

Change From Baseline in HAQ-DI Response at Weeks 4, 8, 12, 16, 20, and 24

Change From Baseline in HAQ-DI Score at Weeks 24, 28, 32, 36, 44, and 56

Change from baseline in HAQ-DI score is a measure of the change in the physical function, where a negative change reflects an improvement and a positive change reflects worsening of physical function. HAQ-DI is a 20-question instrument that assesses the 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 are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning.

Percentage of Participants Who Achieved a HAQ-DI Response With Greater Than or Equal to (>=) 0.3 Improvement From Baseline in HAQ-DI Score at Weeks 4, 8, 12, 16, 20, and 24

HAQ-DI response was defined as >= 0.3 improvement from baseline in HAQ-DI score. HAQ-DI is a 20-question instrument that assesses the 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 are scored from 0 indicating no difficulty, to 3 indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning.

Percentage of Participants Who Achieved an HAQ-DI Response With >= -0.3 Improvement From Baseline in HAQ-DI Score at Weeks 24, 28, 32, 36, 44, and 56

Percent Change From Baseline in Dactylitis Scores at Weeks 4, 8, 16, and 24

Percent Change From Baseline in Dactylitis Scores at Weeks 24, 28, 32, 44, 56

Dactylitis was characterized by swelling of the entire finger or toe. The severity of dactylitis is scored on a scale of 0-3, where 0, 1, 2, 3 indicates none, mild, moderate, severe, respectively in each digit of the hands and feet. The range of total dactylitis scores for a participant is 0-60. Higher score indicates more severe dactylitis. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Percentage of Participants With Dactylitis at Weeks 4, 8, 16, and 24

Percentage of Participants With Dactylitis at Weeks 24, 28, 32, 44, and 56

Percent Change From Baseline in LEI Scores at Week 4, 8, 16, and 24

Percent Change From Baseline in LEI Scores at Weeks 24, 28, 32, 44, and 56

Enthesitis will be assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Percentage of Participants With Enthesitis Based on LEI Score at Weeks 4, 8, 16, and 24 in Participants With Enthesitis at Baseline

Enthesitis was assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. Participants with enthesitis had LEI score >0. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Percentage of Participants With Enthesitis Based on LEI at Weeks 24, 28, 32, 44, and 56 in Participants With Enthesitis at Baseline

Enthesitis will be assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. Participants with enthesitis had LEI score >0. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Change From Baseline in Psoriatic ArthritiS Disease Activity Score (PASDAS) Score at Weeks 16 and 24

Change from baseline in PASDAS score measures the change in disease activity where a negative value indicates an improvement and a positive value indicates worsening of PsA disease activity. PASDAS is a PsA disease activity score that assesses 4 domains (joints, entheses, dactylitis and quality of life) of PsA. PASDAS is a derived score combining Patient's Global Assessment of Disease Activity (arthritis and psoriasis, on a 100-unit VAS), Physician's Global Assessment of Disease Activity (on a 100-unit VAS), swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/L), enthesitis based on LEI (scaled to a 0-6 range), dactylitis count (scoring each digit from 0-3 and recoding to 0-1, where any score > 0 equaled 1), and the PCS score of the SF-36 health survey. The total score range is 0-10 and the cutoffs for disease activity were 3.2 (low) to 5.4 (high). Negative changes from baseline indicate improvement of overall disease activity.

Change From Baseline in PASDAS Score at Weeks 24 and 44

Change From Baseline in GRAppa Composite scorE (GRACE) Index Score at Weeks 16 and 24

Change from baseline in GRACE index score measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates a worsening of PsA disease activity. GRACE index was converted from Arithmetic Mean of the Desirability Function (AMDF). AMDF is calculated by transforming all variables using predefined algorithms and expressing the total score as a mean with a score range of 0 - 1, where 1 indicates a better state than 0. GRACE Index = (1 - AMDF)*10, where GRACE index has a range of 0-10, with higher scores indicate more active disease. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Change From Baseline in GRACE Index Score at Weeks 24 and 44

Change From Baseline in Modified Composite Psoriatic Disease Activity Index (mCPDAI) Score at Weeks 16 and 24

The mCPDAI assessed 4 domains (joints, skin, entheses, and dactylitis). The mCPDAI scores were calculated using the following assessments: joints (66 swollen and 68 tender joint counts), HAQ-DI score, PASI, dactylitis, and enthesitis. Within each domain a score (range 0-3) was assigned, where 0= Not involved, 1= Mild, 2= Moderate and 3= Severe. The scores for each domain were then added together to give a final score range of 0 to 12. A higher score indicates more active disease activity. Negative changes from baseline indicate improvement of PsA disease activity.

Change From Baseline in mCPDAI Index Score at Weeks 24 and 44

Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) Score at Weeks 4, 8, 12, 16, 20 and 24

Change from baseline in DAPSA measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates worsening of disease activity. DAPSA score is a the sum of swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient's Assessment of Pain (on a 10-unit VAS;0=no pain, 10=worst possible pain), and Patient's Global Assessment of Disease Activity (arthritis, on a 10-unit VAS; 0 to 100 centimeter [cm] VAS, 0=excellent and 10=poor). Cut-off values for disease activity: 0-4 remission; 5-14 low; 15-28 moderate; >28 high.

Change From Baseline in DAPSA Index Score at Weeks 24, 28, 32, 36, 44, and 56

Change from baseline in DAPSA measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates worsening of disease activity. DAPSA score is a the sum of swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient's Assessment of Pain (on a 10-unit VAS;0=no pain, 10=worst possible pain), and Patient's Global Assessment of Disease Activity (arthritis, on a 10-unit VAS; 0 to 10cm VAS, 0=excellent and 10=poor). Cut-off values for disease activity: 0-4 remission; 5-14 low; 15-28 moderate; >28 high.

Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Weeks 16 and 24

MDA defines a satisfactory state of disease activity that includes 5 domains of PsA (joint symptoms, skin psoriasis, patient's perspective of pain and disease activity on arthritis and psoriasis, physical function and enthesitis). Participants were classified as achieving MDA if they fulfilled 5 of 7 outcome measures: tender joint count <=1; swollen joint count <=1; PASI <=1; patient pain VAS score of <=15 mm; patient global disease activity on arthritis and psoriasis; VAS score of <=20 mm; Health Assessment Questionnaire score <=0.5; and tender entheseal points <=1.

Percentage of Participants Who Achieved MDA at Weeks 24 and 44

Change From Baseline in the Physical and Mental Component Summary (PCS and MCS) Scores of 36- Item Short Form Health Assessment Questionnaire (SF-36) at Weeks 16 and 24

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The PCS and MCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms as presented in this outcome measure. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

Change From Baseline in the PCS Scores of SF-36 at Weeks 24 and 44

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The PCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms as presented in this outcome measure. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

Change From Baseline in the MCS Scores of SF-36 at Weeks 24 and 44

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The MCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms as presented in this outcome measure. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

Change From Baseline in Norm-based SF-36 Scales at Week 16 and 24

SF-36 evaluates 8 individual subscales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health). Each 8 scales scored from 0 to 100 with higher scores= better health. The scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms. Higher scores indicate better health. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

Change From Baseline in Norm-based SF-36 Scale at Week 24 and 44

Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Score at Weeks 16 and 24

RAPID3 is a multi-dimensional health assessment questionnaire that was designed for use in routine clinical care. Three core data set for function, pain, and patient global estimate of disease activity were recorded. Each was scored 0-10 and the score ranges from 0 to 30 with higher scores indicating worse condition. A negative change from baseline indicates improvement in condition.

Change From Baseline in RAPID3 Score at Weeks 24 and 44

Percentage of Participants Who Achieved a PASI 50, PASI 75, PASI 90 and PASI 100 Response at Weeks 16 and 24

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. PASI 50, 75, 90, and 100 responses were defined as at least a 50%, 75%, 90%, and 100% reduction in PASI relative to Baseline respectively. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Percentage of Participants Who Achieved a PASI 50, PASI 75, PASI 90 and PASI 100 Response at Weeks 24, 28, 32, 44, and 56

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. PASI 50, 75, 90, and 100 responses were defined as at least a 50%, 75%, 90%, and 100% reduction in PASI relative to Baseline respectively.

Percent Change From Baseline in PASI Score at Weeks 4, 8, 16, and 24

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A negative percent change from baseline indicates the percent improvement from baseline in the severity of psoriatic lesions. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Percent Change From Baseline in PASI Score at Weeks 24, 28, 32, 44, and 56

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A negative percent change from baseline indicates the percent improvement from baseline in the severity of psoriatic lesions.

Full Information

NCT ID

NCT02319759

First Posted

December 15, 2014

Last Updated

September 21, 2020

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02319759

Brief Title

Efficacy and Safety Study of Guselkumab in the Treatment of Participants With Active Psoriatic Arthritis (PsA)

Official Title

A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab in the Treatment of Subjects With Active Psoriatic Arthritis

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Completed

Study Start Date

March 27, 2015 (Actual)

Primary Completion Date

May 31, 2016 (Actual)

Study Completion Date

January 17, 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 Drug Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety and tolerability of guselkumab in participants with Active Psoriatic Arthritis (PsA).

Detailed Description

This is a multi-center (more than one clinical site will work on a medical research study), randomized (study medication assigned to participants by chance), double-blind (neither investigator nor participant knows which treatment the participant receives), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) study to determine the efficacy and safety of guselkumab in participants with PsA. The study will consist of 4 parts: Screening period (6 weeks), a double-blind treatment period (consists of guselkumab and placebo treatment for 24 weeks), an active treatment period (guselkumab for 20 weeks), and follow-up period (12 weeks). The maximal study duration for a participant will not exceed 62 weeks including the Screening period. Eligible participants will be randomly assigned to one of two groups in a 2:1 ratio to either receive Guselkumab 100 milligram (mg) at Weeks 0, 4 then every 8 weeks or Placebo at Weeks 0, 4 then every 8 weeks until Week 24. At week 24, participants remaining in the placebo group will start to receive guselkumab 100 mg at Weeks 24, 28, 36 and 44. Participants in both treatment groups who have less than (<) 5 percent (%) improvement from baseline in both tender and swollen joint counts at Week 16 will qualify for early escape and will switch to open-label therapy with ustekinumab 45 mg or 90 mg at Weeks 16, 20, 32, and 44 based on the approved dosage for the PsA indication in the particular country of study. The efficacy will be assessed primarily by measuring percentage of participants who achieve an American College of Rheumatology (ACR) 20 Response at Week 24. Participants' safety will be monitored throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Psoriatic Arthritis

Keywords

Psoriatic Arthritis, Guselkumab, Ustekinumab, Placebo

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

149 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Guselkumab

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Guselkumab

Intervention Description

In the guselkumab group, Guselkumab 100 mg subcutaneous injection will be administered at Weeks 0, 4, 12, 20, 28, 36 and 44. In the placebo group, guselkumab 100 mg subcutaneous injection will be administered at Weeks 24, 28, 36 and 44 for participants remaining on placebo at Week 24.

Intervention Type

Drug

Intervention Name(s)

Ustekinumab

Intervention Description

In both placebo and guselkumab groups, if the participants qualify for early escape, they will switch to receive ustekinumab 45 mg or 90 mg subcutaneous injection at Weeks 16, 20, 32, and 44 based on the approved dosage in the particular country of the study.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

In placebo group, Placebo subcutaneous injection will be administered at Weeks 0, 4, 12, and 20. In guselkumab group, placebo subcutaneous injection will be administered at Week 24 to maintain the blind.

Primary Outcome Measure Information:

Title

Percentage of Participants Who Achieved American College of Rheumatology (ACR) 20 Response at Week 24

Description

Time Frame

Week 24

Secondary Outcome Measure Information:

Title

Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI)-75 Response at Week 24

Description

Time Frame

Week 24

Title

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24

Description

Time Frame

Baseline and Week 24

Title

Percentage of Participants Who Achieved an ACR 20 Response at Week 16

Description

Time Frame

Week 16

Title

Percentage of Participants Who an Achieved ACR 50 Response at Week 24

Description

Time Frame

Week 24

Title

Percent Change From Baseline in Leeds Enthesitis Index (LEI) Scores Among Participants With Enthesitis at Week 24

Description

Time Frame

Baseline and Week 24

Title

Percent Change From Baseline in Dactylitis Scores Among Participants With Dactylitis at Baseline at Week 24

Description

Time Frame

Baseline and Week 24

Title

Percentage of Participants Who Achieved ACR 20, ACR 50, and ACR 70 Responses at Weeks 4, 8, 12, 16, 20, and 24

Description

Time Frame

Weeks 4, 8, 12, 16, 20, and 24

Title

Percentage of Participants Who Achieved ACR 20, ACR 50, and ACR 70 Responses at Weeks 24, 28, 32, 36, 44, and 56

Description

Time Frame

Weeks 24, 28, 32, 36, 44, and 56

Title

Percent Change From Baseline in the ACR Components at Weeks 12 and 24

Description

Time Frame

Baseline and Weeks 12, 24

Title

Percent Change From Baseline in the ACR Components at Weeks 24, 28, 32, 36, 44 and 56

Description

Time Frame

Basline and Weeks 24, 28, 32, 36, 44, 56

Title

Change From Baseline in HAQ-DI Response at Weeks 4, 8, 12, 16, 20, and 24

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 24

Title

Change From Baseline in HAQ-DI Score at Weeks 24, 28, 32, 36, 44, and 56

Description

Change from baseline in HAQ-DI score is a measure of the change in the physical function, where a negative change reflects an improvement and a positive change reflects worsening of physical function. HAQ-DI is a 20-question instrument that assesses the 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 are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area (that is, lower scores are indicative of better functioning). The total HAQ-DI score ranges from 0-24 with lower score indicating better functioning.

Time Frame

Baseline and Weeks 24, 28, 32, 36, 44, 56

Title

Percentage of Participants Who Achieved a HAQ-DI Response With Greater Than or Equal to (>=) 0.3 Improvement From Baseline in HAQ-DI Score at Weeks 4, 8, 12, 16, 20, and 24

Description

Time Frame

Weeks 4, 8, 12, 16, 20, and 24

Title

Percentage of Participants Who Achieved an HAQ-DI Response With >= -0.3 Improvement From Baseline in HAQ-DI Score at Weeks 24, 28, 32, 36, 44, and 56

Description

Time Frame

Weeks 24, 28, 32, 36, 44, 56

Title

Percent Change From Baseline in Dactylitis Scores at Weeks 4, 8, 16, and 24

Description

Time Frame

Baseline and Weeks 4, 8, 16, 24

Title

Percent Change From Baseline in Dactylitis Scores at Weeks 24, 28, 32, 44, 56

Description

Time Frame

Baseline and Weeks 24, 28, 32, 44, 56

Title

Percentage of Participants With Dactylitis at Weeks 4, 8, 16, and 24

Description

Time Frame

Weeks 4, 8, 16, and 24

Title

Percentage of Participants With Dactylitis at Weeks 24, 28, 32, 44, and 56

Description

Time Frame

Weeks 24, 28, 32, 44, and 56

Title

Percent Change From Baseline in LEI Scores at Week 4, 8, 16, and 24

Description

Time Frame

Baseline and Weeks 4, 8, 16, 24

Title

Percent Change From Baseline in LEI Scores at Weeks 24, 28, 32, 44, and 56

Description

Time Frame

Baseline and Weeks 24, 28, 32, 44, 56

Title

Percentage of Participants With Enthesitis Based on LEI Score at Weeks 4, 8, 16, and 24 in Participants With Enthesitis at Baseline

Description

Time Frame

Weeks 4, 8, 16, and 24

Title

Percentage of Participants With Enthesitis Based on LEI at Weeks 24, 28, 32, 44, and 56 in Participants With Enthesitis at Baseline

Description

Enthesitis will be assessed using the Leeds Enthesitis Index (LEI). The LEI was developed to assess enthesitis in participants with PsA, and evaluates the presence (score of 1) or absence of pain (score of 0) by applying local pressure to Lateral elbow epicondyle, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. Participants with enthesitis had LEI score >0. LEI scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

Time Frame

Weeks 24, 28, 32, 44, and 56

Title

Change From Baseline in Psoriatic ArthritiS Disease Activity Score (PASDAS) Score at Weeks 16 and 24

Description

Time Frame

Baseline and Weeks 16, 24

Title

Change From Baseline in PASDAS Score at Weeks 24 and 44

Description

Time Frame

Baseline and Weeks 24, 44

Title

Change From Baseline in GRAppa Composite scorE (GRACE) Index Score at Weeks 16 and 24

Description

Time Frame

Baseline and Weeks 16, 24

Title

Change From Baseline in GRACE Index Score at Weeks 24 and 44

Description

Time Frame

Baseline and Weeks 24, 44

Title

Change From Baseline in Modified Composite Psoriatic Disease Activity Index (mCPDAI) Score at Weeks 16 and 24

Description

Time Frame

Baseline and Weeks 16, 24

Title

Change From Baseline in mCPDAI Index Score at Weeks 24 and 44

Description

Time Frame

Baseline and Weeks 24, 44

Title

Change From Baseline in Disease Activity Index for Psoriatic Arthritis (DAPSA) Score at Weeks 4, 8, 12, 16, 20 and 24

Description

Time Frame

Baseline and Weeks 4, 8, 12, 16, 20, 24

Title

Change From Baseline in DAPSA Index Score at Weeks 24, 28, 32, 36, 44, and 56

Description

Change from baseline in DAPSA measures the change in disease activity, where a negative change indicates an improvement and a positive change indicates worsening of disease activity. DAPSA score is a the sum of swollen joint count (66 joints), tender joint count (68 joints), CRP (mg/dL), Patient's Assessment of Pain (on a 10-unit VAS;0=no pain, 10=worst possible pain), and Patient's Global Assessment of Disease Activity (arthritis, on a 10-unit VAS; 0 to 10cm VAS, 0=excellent and 10=poor). Cut-off values for disease activity: 0-4 remission; 5-14 low; 15-28 moderate; >28 high.

Time Frame

Baseline and Weeks 24, 28, 32, 36, 44, 56

Title

Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Weeks 16 and 24

Description

Time Frame

Weeks 16 and 24

Title

Percentage of Participants Who Achieved MDA at Weeks 24 and 44

Description

Time Frame

Weeks 24 and 44

Title

Change From Baseline in the Physical and Mental Component Summary (PCS and MCS) Scores of 36- Item Short Form Health Assessment Questionnaire (SF-36) at Weeks 16 and 24

Description

Time Frame

Baseline and Weeks 16, 24

Title

Change From Baseline in the PCS Scores of SF-36 at Weeks 24 and 44

Description

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The PCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms as presented in this outcome measure. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

Time Frame

Baseline and Weeks 24, 44

Title

Change From Baseline in the MCS Scores of SF-36 at Weeks 24 and 44

Description

SF-36 is a multi-domain instrument with 36 items to evaluate the health status and quality of life. It included 8 subscales (physical functioning, physical role functioning, bodily pain, general health perception, vitality, social functioning, emotional role functioning, and mental health), which yielded a Physical Component Summary (PCS) with score range 0-100 (higher score-better quality of life) and a Mental Component Summary (MCS) with score range 0-100 (higher score-better quality of life) in addition to subscale scores. The MCS scores are normalized to a mean of 50 and standard deviations of 10, based upon general US population norms as presented in this outcome measure. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

Time Frame

Baseline and Weeks 24, 44

Title

Change From Baseline in Norm-based SF-36 Scales at Week 16 and 24

Description

Time Frame

Baseline and Weeks 16, 24

Title

Change From Baseline in Norm-based SF-36 Scale at Week 24 and 44

Description

Time Frame

Baseline and Weeks 24, 44

Title

Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID3) Score at Weeks 16 and 24

Description

Time Frame

Baseline and Weeks 16, 24

Title

Change From Baseline in RAPID3 Score at Weeks 24 and 44

Description

Time Frame

Baseline and Weeks 24, 44

Title

Percentage of Participants Who Achieved a PASI 50, PASI 75, PASI 90 and PASI 100 Response at Weeks 16 and 24

Description

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. PASI 50, 75, 90, and 100 responses were defined as at least a 50%, 75%, 90%, and 100% reduction in PASI relative to Baseline respectively. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Time Frame

Weeks 16 and 24

Title

Percentage of Participants Who Achieved a PASI 50, PASI 75, PASI 90 and PASI 100 Response at Weeks 24, 28, 32, 44, and 56

Description

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. PASI 50, 75, 90, and 100 responses were defined as at least a 50%, 75%, 90%, and 100% reduction in PASI relative to Baseline respectively.

Time Frame

Weeks 24, 28, 32, 44, and 56

Title

Percent Change From Baseline in PASI Score at Weeks 4, 8, 16, and 24

Description

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A negative percent change from baseline indicates the percent improvement from baseline in the severity of psoriatic lesions. As planned, results data was analyzed and reported for the specified arms for this outcome measure.

Time Frame

Baseline and Weeks 4, 8, 16, 24

Title

Percent Change From Baseline in PASI Score at Weeks 24, 28, 32, 44, and 56

Description

The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72. A negative percent change from baseline indicates the percent improvement from baseline in the severity of psoriatic lesions.

Time Frame

Baseline and Weeks 24, 28, 32, 44, 56

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Has had Psoriatic Arthritis (PsA) for at least 6 months before the first administration of study drug and meet classification criteria for Psoriatic Arthritis (CASPAR) at Screening Had active PsA as defined by: At least 3 swollen joints and at least 3 tender joints at Screening and at baseline C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram (mg)/deciliter (dL) at Screening from the central laboratory Has at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis Has plaque psoriasis with body surface area (BSA) involvement greater than or equal to (>=) 3% at Screening and baseline Has active PsA despite current or previous non-biologic disease-modifying antirheumatic drugs (DMARD), oral corticosteroid, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy If using methotrexate (MTX), oral corticosteroids or NSAIDs, the dose must be stable Exclusion Criteria: Have other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus, or Lyme disease Has previously received guselkumab or ustekinumab Has received more than 1 type of biologic anti-tumor necrosis factor (TNF) agent previously Have received infliximab (or its biosimilars) or golimumab intraveneous (IV) within 12 weeks before the first administration of study drug Have received adalimumab (or its biosimilars), golimumab subcutaneous (SC), certolizumab pegol or etanercept (or its biosimilars) within 8 weeks before the first administration of study drug

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

Huntsville

State/Province

Alabama

Country

United States

City

Trumbull

State/Province

Connecticut

Country

United States

City

Clearwater

State/Province

Florida

Country

United States

City

Tampa

State/Province

Florida

Country

United States

City

Sandy Springs

State/Province

Georgia

Country

United States

City

Indianapolis

State/Province

Indiana

Country

United States

City

Boston

State/Province

Massachusetts

Country

United States

City

Edina

State/Province

Minnesota

Country

United States

City

Saint Louis

State/Province

Missouri

Country

United States

City

Wyomissing

State/Province

Pennsylvania

Country

United States

City

Jackson

State/Province

Tennessee

Country

United States

City

Arlington

State/Province

Virginia

Country

United States

City

Barrie

State/Province

Ontario

Country

Canada

City

London

State/Province

Ontario

Country

Canada

City

Peterborough

State/Province

Ontario

Country

Canada

City

Waterloo

State/Province

Ontario

Country

Canada

City

Berlin

Country

Germany

City

Hamburg

Country

Germany

City

Herne

Country

Germany

City

Kiel

Country

Germany

City

Köln

Country

Germany

City

Lubeck

Country

Germany

City

Bialystok

Country

Poland

City

Elblag

Country

Poland

City

Poznań

Country

Poland

City

Warszawa

Country

Poland

City

Bucharest

Country

Romania

City

Bataysk

Country

Russian Federation

City

Moscow

Country

Russian Federation

City

Novosibirsk

Country

Russian Federation

City

Ryazan

Country

Russian Federation

City

Saratov

Country

Russian Federation

City

St. Petersburg

Country

Russian Federation

City

Ufa

Country

Russian Federation

City

Ulyanovsk

Country

Russian Federation

City

Yaroslavl

Country

Russian Federation

City

Barcelona

Country

Spain

City

Madrid

Country

Spain

City

Sabadell

Country

Spain

City

Santiago de Compostela

Country

Spain

City

Sevilla

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

32665433

Citation

Mease PJ, Gladman DD, Deodhar A, McGonagle DG, Nash P, Boehncke WH, Gottlieb A, Xu XL, Xu S, Hsia EC, Karyekar CS, Helliwell PS. Impact of guselkumab, an interleukin-23 p19 subunit inhibitor, on enthesitis and dactylitis in patients with moderate to severe psoriatic arthritis: results from a randomised, placebo-controlled, phase II study. RMD Open. 2020 Jul;6(2):e001217. doi: 10.1136/rmdopen-2020-001217.

Results Reference

derived

PubMed Identifier

31421033

Citation

Helliwell PS, Deodhar A, Gottlieb AB, Boehncke WH, Xu XL, Xu S, Wang Y, Hsia EC, Gladman DD, Ritchlin CT. Composite Measures of Disease Activity in Psoriatic Arthritis: Comparative Instrument Performance Based on the Efficacy of Guselkumab in an Interventional Phase II Trial. Arthritis Care Res (Hoboken). 2020 Nov;72(11):1579-1588. doi: 10.1002/acr.24046.

Results Reference

derived

PubMed Identifier

29893222

Citation

Deodhar A, Gottlieb AB, Boehncke WH, Dong B, Wang Y, Zhuang Y, Barchuk W, Xu XL, Hsia EC; CNTO1959PSA2001 Study Group. Efficacy and safety of guselkumab in patients with active psoriatic arthritis: a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2018 Jun 2;391(10136):2213-2224. doi: 10.1016/S0140-6736(18)30952-8. Epub 2018 Jun 1.

Results Reference

derived

Learn more about this trial

Efficacy and Safety Study of Guselkumab in the Treatment of Participants With Active Psoriatic Arthritis (PsA)

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