Arthritis, Psoriatic
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy of guselkumab plus golimumab combination treatment in participants with active psoriatic arthritis (PsA) and inadequate response (IR) to prior anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapies by assessing clinical response compared with guselkumab monotherapy.
Detailed description
PsA is a chronic inflammatory multi-faceted disease that impacts the peripheral and axial joints, soft tissues, and skin. Guselkumab is a fully human monoclonal antibody (mAb) directed against the p19 subunit of interleukin (IL)-23, blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23 specific intracellular signaling, subsequent activation, and cytokine production. Golimumab is a fully human anti-TNF-alpha mAb that binds to TNF-alpha with high affinity, prevents binding to its receptors, thereby inhibiting the biological activity of TNF-alpha and resulting in limited production or activity of inflammatory cytokines, thereby providing therapeutic benefit in various chronic inflammatory disorders, including PsA. This study will consist of a Screening Phase (up to 6 weeks), Double-blind Phase from Weeks 0 to 24 which includes the active treatment phase and the primary efficacy visit (Week 24), and Safety Follow-up Phase from Week 24 to Week 36. Key safety assessments will include adverse events (AEs), clinical laboratory safety tests (hematology and chemistry), vital signs, monitoring for injection-site and hypersensitivity reactions, and early detection of active tuberculosis (TB). The total duration of the study is up to 42 weeks.
Interventions
DRUGGuselkumab
Guselkumab will be administered as a SC injection.
DRUGGolimumab
Golimumab will be administered as a SC injection.
DRUGPlacebo
Placebo will be administered as a SC injection.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of psoriatic arthritis (PsA) for greater than or equal to (\>=) 6 months prior to the first administration of study intervention and meet Classification criteria for PsA (CASPAR) criteria at screening * Have active PsA as defined by having at least 3 swollen joints and at least 3 tender joints at screening and at baseline * Have at least 1 of the following PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis * Have active plaque psoriasis, with at least one psoriatic plaque of \>=2 centimeter (cm) diameter or nail changes consistent with psoriasis * Have an inadequate response (IR) to anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy, defined as presence of active PsA despite treatment with either 1 or 2 prior anti-TNF-alpha agent(s) and the following: a. Lack of benefit to either 1 or 2 prior anti-TNF-alpha therapies, as documented in the participant history by the treating physician, after at least 12 weeks of etanercept, adalimumab, or certolizumab pegol therapy, or at least 14-weeks of infliximab, or any biosimilar of these 4 therapies. Documented lack of benefit may include inadequate improvement in joint counts, physical function, or disease activity; b. The last dose of anti-TNF-alpha therapy must have occurred greater than 5 half-lives of the drug prior to first study intervention administration (washout period)
Exclusion criteria
* Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab and/or golimumab therapy, including but not limited to rheumatoid arthritis (RA), ankylosing spondylitis (AS), nonradiographic axial spondyloarthritis (nr AxSpA), systemic lupus erythematosus, or lyme disease * Has known intolerance or hypersensitivity to any biologic medication, or known allergies or clinically significant reactions to murine, chimeric, or human proteins, monoclonal antibodies (mAb), or antibody fragments * Has received prior treatment with golimumab or guselkumab or has documented intolerance to prior anti-TNF-alpha therapy in the participant history by the treating physician * Has received more than 2 prior anti-TNF-alpha agents (or biosimilars) * Positive human immunodeficiency virus (HIV) antibody test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Week 24 | Week 24 | MDA was a measure that defines a satisfactory state of disease activity that includes 5 domains of psoriatic arthritis (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 the following 7 criteria at that visit: Tender joint count (68 joints) \<=1, Swollen joint count (66 joints) \<=1, Psoriasis activity and severity index (PASI) \<=1, Patient's Assessment of Pain \<=15 on a 100-unit visual analog scale (VAS), Patient's Global Assessment of Disease Activity (arthritis and psoriasis) \<=20 on a 100-unit VAS, Disability Index of the Health Assessment Questionnaire (HAQ-DI) score \<=0.5, and Tender entheseal points \<= 1 (Leeds Enthesitis Index \[LEI\] score \<= 1). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved American College of Rheumatology (ACR) 50 at Week 24 | Week 24 | ACR 50 response was defined as greater than or equal to (\>=) 50% improvement from baseline in both swollen joint (66 joints) and tender joint counts (68 joints) and \>=50% improvement from baseline in \>=3 of 5 assessments: Physician global assessment of disease activity (0 to 100 millimeters \[mm\] VAS \[0=no arthritis activity and 100=extremely active arthritis\]), Patient global assessment of disease activity (arthritis) (100 mm VAS \[0 = no limitation of normal activities; 100 = very poor\]), Patient's global assessment of pain (100 mm VAS \[0 = no pain; 100 = most severe pain\]), patient's assessment of physical function measured by HAQ-DI (20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and high-sensitivity C-reactive protein (hsCRP). |
| Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Week 16 | Week 16 | MDA was a measure that 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 the following 7 criteria at that visit: Tender joint count (68 joints) \<=1, Swollen joint count (66 joints) \<=1, PASI \<=1, Patient's Assessment of Pain \<=15 on a 100-unit VAS, Patient's Global Assessment of Disease Activity (arthritis and psoriasis) \<=20 on a 100-unit VAS, HAQ-DI score \<=0.5, and Tender entheseal points \<= 1 (LEI score \<= 1). |
| Percentage of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 90 Response at Week 24 Among Participants With >= 3% Body Surface Area (BSA) Psoriatic Involvement and an Investigator Global Assessment (IGA) Score of >=2 (Mild) at Baseline | Week 24 | PASI 90 response was defined as at least a 90% reduction in PASI relative to baseline. PASI was a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body was divided into 4 regions: head and neck, trunk (including axillae and groin), upper extremities, and lower extremities (included buttocks). Each of these areas was 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 to 100% involvement), and erythema, induration and scaling, each rated on a scale of 0 to 4, that was none to maximum severity. PASI produces a numeric score range from 0 (no psoriasis) to 72 (worst condition). Higher scores indicated more severe disease. |
| Percentage of Participants Who Achieved PASI 100 Response at Week 24 Among the Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline | Week 24 | PASI 100 response was defined as 100% reduction in PASI relative to baseline. PASI was a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body was divided into 4 regions: head and neck, trunk (including axillae and groin), upper extremities, and lower extremities (included buttocks). Each of these areas was 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 to 100% involvement), and erythema, induration and scaling, each rated on a scale of 0 to 4, that was none to maximum severity. PASI produces a numeric score range from 0 (no psoriasis) to 72 (worst condition). Higher scores indicated more severe disease. |
| Percentage of Participants With an IGA-psoriasis Response at Week 24 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline | Week 24 | IGA psoriasis response was defined as an IGA psoriasis score of 0 (cleared) or 1 (minimal) and \>=2 grade reduction from baseline in the IGA psoriasis score. The IGA documents the investigator's assessment of the participant's psoriasis at a given time point. Overall lesions were graded for induration, erythema, and scaling each using a 5 point scale: clear (0), minimal (1), mild (2), moderate (3), and severe (4). The IGA score of psoriasis was based upon the average of induration, erythema, and scaling scores. The participant's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). |
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24 | Baseline (Week 0), Week 24 | Change from baseline in HAQ-DI score was a measure of the change in the physical function. It consists of a 20-questions instrument that assesses the degree of difficulty a person had 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 = no difficulty to 3= inability to perform a task. Scores on each task were summed and averaged to provide an overall HAQ-DI total score ranging from 0 (least difficulty) to 3 (extreme difficulty). Lower scores indicated better functioning. Negative change from baseline indicated improvement of physical function. |
| Percentage of Participants Who Had Resolution of Enthesitis at Week 24 Among the Participants With Enthesitis at Baseline | Week 24 | Enthesitis assessed using the Leeds Enthesitis Index (LEI), a tool developed to assess enthesitis in participants with PsA and evaluates the presence (score of 1) or absence (score of 0) of tenderness by applying local pressure to the following enthesis sites: left and right lateral epicondyle humerus, left and right medial femoral condyle, and left and right achilles tendon insertion. Each site was scored as 1 if tenderness was present or 0 if tenderness was absent. The enthesitis index score was a total score of the 6 evaluated sites from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness). Higher score indicated more sites with tenderness. A LEI score of 0 at a post baseline visit indicates resolution of enthesitis when baseline LEI \>0. |
| Percentage of Participants Who Achieved Resolution of Dactylitis Response at Week 24 Among the Participants With Dactylitis at Baseline | Week 24 | Dactylitis was characterized by swelling in both hands and feet. The severity of dactylitis was scored on a scale from 0 to 3 (0-no dactylitis, 1-mild dactylitis, 2-moderate dactylitis, and 3-severe dactylitis) for each digit. The results for each digit summed to produce final dactylitis score which was from 0 to 60. Higher score indicates more severe dactylitis. Dactylitis count was derived based on dactylitis score, each score was recorded to 0 or 1 from 0 to 3, where any score \>0 was recorded as 1. For resolution of dactylitis, it was defined as participants who had a dactylitis score greater than 0 at baseline and a score of 0 at the analysis visit. |
| Change From Baseline in Short Form Health Survey (SF-36) Physical Component Score (PCS) at Week 24 | Baseline (Week 0), Week 24 | SF-36 was a multi-domain instrument with 36 items to evaluate 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). The scores for the 8 domains were combined into two summary scores: the physical component summary (PCS) score and the mental component summary (MCS) score. Domains 1 to 4 primarily contribute to the PCS score of the SF-36. Domains 5-8 primarily contributes to the MCS score of the SF-36. Each of the 8 domain scores and the component summary score ranged from 0=worst to 100=best. Higher scores represent better health status. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life. |
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) | From Week 0 up to Week 36 | An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were any AE occurred at or after the initial administration of study intervention through the day of last dose plus 16 weeks. |
| Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs) | From Week 0 up to Week 36 | SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, led to a congenital anomaly/birth defect in the offspring of a participant, or was an important medical event. TESAEs were any SAE occurred at or after the initial administration of study intervention through the day of last dose plus 16 weeks. |
| Percentage of Participants With Reasonably Related Adverse Events (AEs) | From Week 0 up to Week 36 | Percentage of participants with reasonably related AEs was reported. An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. AE reasonably related to guselkumab or golimumab were defined as AEs classified by the investigator as related to study agent. |
| Percentage of Participants With AEs Leading to Discontinuation of Study Intervention | From Week 0 to Week 20 | Percentage of participants with AEs leading to discontinuation of study intervention was reported. AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. |
| Percentage of Participants With Infections | From Week 0 up to Week 36 | Percentage of participants with infections was reported. Investigators evaluate participants for any signs or symptoms of infection. An AE was any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. |
| Percentage of Participants With Injection-site Reactions | From Week 0 up to Week 36 | Percentage of participants with injection-site reaction was reported. A study intervention injection-site reaction was any adverse reaction at a subcutaneous study intervention injection-site. The injection sites were evaluated for reactions, and any injection-site reaction was recorded as an AE. Injection site reactions were significant bruising, erythema, hemorrhage, irritation, pain, and pruritus. |
| Group 1: Guselkumab Plus Golimumab - Serum Concentration of Golimumab | Weeks 0, 4, 8, 12, 16, 20, 24, and 36 | Serum concentration of golimumab was reported. |
| Serum Concentration of Guselkumab | Weeks 0, 4, 8, 12, 16, 20, 24, and 36 | Serum concentration of guselkumab was reported. |
| Percentage of Participants With Anti-Guselkumab Antibodies | From Week 0 up to Week 36 | Percentage of participants with anti-guselkumab antibodies was reported. |
| Percentage of Participants With Anti-Golimumab Antibodies | From Week 0 up to Week 36 | Percentage of participants with anti-golimumab antibodies were reported. |
Countries
Denmark, France, Hungary, Italy, Poland, Russia, Spain, Sweden, Ukraine, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 88 Participants |
| Age, Continuous | 50.2 Years STANDARD_DEVIATION 10.53 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 89 Participants |
| Region of Enrollment Denmark | 12 Participants |
| Region of Enrollment France | 1 Participants |
| Region of Enrollment Hungary | 1 Participants |
| Region of Enrollment Italy | 4 Participants |
| Region of Enrollment Poland | 2 Participants |
| Region of Enrollment Russian Federation | 2 Participants |
| Region of Enrollment Spain | 22 Participants |
| Region of Enrollment Ukraine | 3 Participants |
| Region of Enrollment United States | 31 Participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 32 |
| other Total, other adverse events | 25 / 59 | 10 / 32 |
| serious Total, serious adverse events | 4 / 59 | 0 / 32 |
Outcome results
None listed