Musculoskeletal Diseases

All Conditions

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Infections

Rare Diseases

Arthritis

Arthritis, Psoriatic

Necrosis

Joint Diseases

Spondylarthropathies

Spondylitis

Spondylarthritis

Spinal Diseases

Bone Diseases

Psoriasis

Skin Diseases

Skin Diseases, Papulosquamous

Spondylarthropathy

Central Nervous System Depressants

All Drugs and Chemicals

Other Dietary Supplements

Benzocaine

Tannic Acid

Participants will receive guselkumab and placebo subcutaneously (SC) to maintain the blind.

Participants will receive placebo SC and will cross over to receive guselkumab SC.

Participants will receive guselkumab as SC injection.

Guselkumab

Participants will receive matching placebo as SC injection.

Placebo

Study Contact

Janssen Research & Development, LLC Clinical Trial

The purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active psoriatic arthritis (PsA) and inadequate response (IR) and/or intolerance to a prior anti-tumor necrosis factor (TNF) by assessing the reduction in signs and symptoms of PsA.

PsA is a chronic, immune-mediated inflammatory disease characterized by peripheral joint inflammation, enthesitis, dactylitis, axial disease, and the skin lesions associated with psoriasis. Guselkumab is a fully human monoclonal antibody (mAb) that binds to p19 protein subunit of interleukin (IL)-23 and 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. The primary hypothesis of this study is that guselkumab is superior to placebo as assessed by the proportion of participants who had an inadequate response (IR) and/or intolerance to one prior anti-tumor necrosis factor (anti-TNF) achieving an American College of Rheumatology 20 (ACR 20) response at Week 24. This study will consist of a screening phase (up to 6 weeks), blinded treatment phase (approximately up to 2 years), which includes a placebo-controlled period from Week 0 to Week 24, and an active-controlled treatment phase from Week 24 to Week 100, and safety follow-up phase (Week 112). Safety assessments will include physical examinations, vital signs, height, weight, electrocardiograms, and clinical safety laboratory assessments. The total duration of the study will be up to 118 weeks.

Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent

A Phase 3B, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Who Had an Inadequate Response and/or Intolerance to One Prior Anti-Tumor Necrosis Factor Alpha Agent

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent (%) improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent (%) improvement from baseline in 3 of following 5 assessments: participant's assessment of pain using Visual Analog Scale (VAS; 0-100 millimeter \[mm\], 0 mm=no pain and 100 mm=worst possible pain), participant's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, \[0 mm= very well to 100 mm= very poor\]), physician's global assessment of disease activity using VAS (scale ranges from 0 to 100), \[0 = no arthritis to 100 = extremely active arthritis\], participant's assessment of physical function measured by Health Assessment Questionnaire-disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and CRP.

Psoriasis response is defined as an Investigator's Global Assessment (IGA) psoriasis score of 0 (cleared) or 1 (minimal) and \>=2- grade reduction from baseline. The IGA documents the investigator's assessment of the participants psoriasis and lesions are graded for induration, erythema and scaling, each using a 5-point scale: 0 (no evidence), 1 (minimal), 2 (mild), 3 (moderate), and 4 (severe). 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).

Psoriasis Area and Severity Index (PASI) is a tool to assess and grade severity of psoriasis and response to therapy. In PASI, body is divided into 4 areas: head, trunk, upper extremities, lower extremities. Each area is assessed separately for percentage of area involved and translated to numeric score ranging from 0 (no involvement) to 6 (90 to 100% involvement), and for erythema, induration, and scaling, each rated on scale of 0 to 4 that is none to maximum severity. PASI numeric score range from 0 (no psoriasis) to 72. Higher scores indicate more severe disease. A PASI 90 response: \>=90% improvement in PASI score from baseline.

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 are 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.

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 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. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

The FACIT-F is a questionnaire that assesses self-reported tiredness, weakness, and difficulty conducting usual activities due to fatigue. The subscale consists 13-item instrument to measure fatigue. Each of the 13 items has a set of five response categories: Not at all (=0), A little bit (=1), Somewhat (=2), Quite a bit (=3) and Very much (=4). A total FACIT-Fatigue subscale score is calculated as the sum of the 13 item scores (reserved scores \[4 - score\]) and ranges from 0 to 52, with a higher score indicating less fatigue. Positive changes from baseline indicate improvement of fatigue. Items are reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue.

MDA is considered achieved if at least 5 of the following 7 criteria were met at the analysis visit: tender joint count \<=1; swollen joint count \<=1; psoriasis activity and severity index \<=1; patient's pain VAS score of \<=15; patient's global disease activity VAS (arthritis and psoriasis) score of \<=20; HAQ-DI \<=0.5; and tender entheseal points \<=1.

ACR 20 response: \>=20% improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and \>=20% improvement from baseline in 3 of 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0=indicating no difficulty, 3=indicating inability to perform task in that area), and CRP.

ACR 50 response is defined as \>=50% improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and \>=50% improvement from baseline in 3 of 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI; a 20-question instrument assessing 8 functional areas; range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP.

ACR 50 response is defined as \>=50 percent (%) improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and \>=50% improvement from baseline in 3 of 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI; a 20-question instrument assessing 8 functional areas; range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP.

ACR 70 response is defined as \>= 70% improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and \>=70% improvement from baseline in 3 of 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI; a 20-question instrument assessing 8 functional areas; range: 0-3, 0=no difficulty, 3=inability to perform a task in that area), and CRP.

Percentage of participants with AEs, SAEs reasonably related AEs will be assessed. 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. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, and suspects transmission of any infectious agent via a medicinal product. Reasonably related AEs are those AEs which are judged related to study treatment by the investigator.

Percentage of participants with AEs leading to discontinuation of study intervention will be reported.

Percentage of participants with infections will be reported.

Percentage of participants with injection-site reactions will be reported. An injection-site reaction is any adverse reaction at a subcutaneous (SC) study intervention injection-site.

Percentage of participants with change from baseline in clinical laboratory abnormalities including chemistry and hematology will be reported.

Percentage of participants with laboratory abnormalities (hematology, chemistry) with maximum toxicity grades as per CTCAE 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.

Serum guselkumab concentration will be measured.

Percentage of participants with anti-guselkumab antibodies to guselkumab will be reported.

Janssen Research & Development, LLC

Nutritional and Metabolic Diseases

Immune System Diseases

Obesity

Arthritis, Rheumatoid

Spondylitis, Ankylosing

Communicable Diseases

Bone Diseases, Infectious

Rheumatic Diseases

Collagen Diseases

Connective Tissue Diseases

Autoimmune Diseases

Axial Spondyloarthritis

Ankylosis

Anti-Inflammatory Agents

Antirheumatic Agents

Dermatologic Agents

Gastrointestinal Agents

Tumor Necrosis Factor Inhibitors

Adalimumab

Infliximab

Patients with Rheumatoid Artritis, Psoriatic Arthritis, Anchylosing Spondylitis starting treament with infliximab or adalimumab

Karen B Lauridsen, MD

Lene Dreyer, MD, Prof.

The aim of the study is to explore whether the influence of gender, tobacco smoking and obesity on treatment response in tumor necrosis factor inhibitors (TNFIs) can be explained by high degree of inflammation, human leucocyte antigen (HLA) type, autoantibodies, TNF and TNFI concentration and presence of ADA.

Tumor necrosis factor inhibitors (TNFIs) have been uses with success since 1999 in Denmark in treatment of various inflammatory diseases, eg. rheumatoid arthritis (RA), Chrohn's disease, psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

TNFIs block a central cytokine in the inflammatory process, tumor necrosis factor (TNF).

Because the drugs are large proteins, they are prone to trigger an immune response and elicit anti-drug antibodies(ADA).

Epidemiologic studies have revealed that groups of patients (women, tobacco smokers, obese patients) with inflammatory rheumatic diseases have a lower response to TNFIs. The reasons for this are not fully elucidated. The hypothesis is that immunogenicity and changed pharmacokinetic of TNFI are causes of the inferior response.

The investigators will carry out a prospective clinical studies of 120 arthritis patients (RA, PsA and AS) initiating treatment with adalimumab or infliximab. The patients will be followed for 12 months and will be registered in DANBIO as normal praxis. Blood samples will be collected at baseline, 2, 4 and 12 months or at termination of the treatment.

Genotypes, autoantibodies, inflammation markers, TNFI and ADA will be measured.

The aim of the study is to explore:

A: If differences between men and women with respect to different markers of inflammation, human leucocyte antigen (HLA), autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment among women.

B: If differences between smokers and non-smokers with respect to different markers of inflammation, HLA, autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment among patients with arthritis who smoke tobacco.

C: If differences between obese and normal weight patients with respect to different markers of inflammation, HLA, autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment.

The study will contribute with new knowledge, which hopefully can make the treatment more personalized and efficient.

EDTA Whole Blood EDTA-plasma, EDTA-buffy coat, serum.

Characterization of Immunogenicity of TNF Inhibitors in Arthritis Patients With Poorer Treatment Response.

Characterization of Immunogenicity of Tumor Necrosis Factor Inhibitors in Arthritis Patients With Poorer Treatment Response Due to Gender, Obesity and Smoking Status.

Changes in disease activity score according to the diagnose. A reduction in the disease activity score indicates a good treatment response.

* Disease Activity Score 28 joints with C-reactive protein (DAS28-CRP)
* Disease Activity in Psoriasis Arthritis (DAPSA)
* Ankylosing Spondylitis Activity Score (ASDAS)
* Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
* Bath Ankylosin Spondylitis Functional Index (BASFI)

Antibodies directed against infliximab or adalimumab. Concentration of anti-drug-antibodies

Plasma koncentration of infliximab or adalimumab

Genomic determination of Human Leucocyte antigens

Aalborg University Hospital

Principal Investigator

Participants will receive guselkumab 100 milligram (mg) Subcutaneous (SC) injection at Weeks 0, 4, 12, 20, 28, 36, and 44 and placebo SC at Week 24 to maintain the blind. At Week 16, Participants who meet the early escape criteria will receive placebo at Week 16 and guselkumab at Week 20, then guselkumab every 8 weeks (q8w).

Participants will receive placebo SC injection at Weeks 0, 4, 12, and 20, and will crossover to receive guselkumab 100 mg SC injection at Weeks 24, 28, 36, and 44. At Week 16, Participants who meet the early escape criteria will receive guselkumab at Weeks 16 and 20, then guselkumab q8w.

Participants will receive guselkumab 100mg as SC injection.

Guselkumab 100 mg

Participants will receive placebo as SC injection.

Janssen Pharmaceutica N.V., Belgium Clinical Trial

The purpose of this study is to evaluate guselkumab efficacy versus placebo in participants with active psoriatic arthritis (PsA) and an inadequate response to Anti-Tumor Necrosis Factor Alpha (TNF-alpha) therapy by assessing the reduction in signs and symptoms of joint disease.

Psoriatic arthritis is a multi-faceted disease that impacts the joints, soft tissues, and skin, all of which not only results in functional disability and impaired quality of life, but participants with this disease also have increased mortality. Guselkumab is a monoclonal antibody that binds to human interleukin 23 (IL-23) and inhibits IL-23 specific intracellular signaling and subsequent activation and cytokine production. Investigation of guselkumab in this Phase 3b PsA clinical study is supported by the favorable efficacy and safety results from Phase 2 study of guselkumab in PsA and Phase 2 and Phase 3 studies in psoriasis including the subset of participants with PsA. The primary hypothesis is that guselkumab 100 milligram (mg) at Weeks 0, 4, and every 8 weeks (q8w) thereafter is superior to placebo which will be assessed by the proportion of participants achieving an American College of Rheumatology (ACR 20) response at Week 24. The study includes 2 periods: A 24-week double-blind, placebo-controlled period for the primary analysis of the efficacy and safety of guselkumab, compared with placebo and a 32-week active-treatment and safety follow-up period for additional analysis of the efficacy and safety of guselkumab. Safety will be monitored throughout the study (Up to Week 56).

A Study of Guselkumab in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNF Alpha) Therapy

Phase 3b, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNFα) Therapy

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials\\transparency.

As noted on this site, requests for access to the study data can be submitted through Yale open Access (YODA) Project site at yoda.yale.edu

The ACR 20 Response is defined as greater than or equal to (\>=) 20 percent (%) improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=20 percent improvement in 3 of following 5 assessments: participant's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), participant's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and C-reactive protein (CRP).

The 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 to 3 (0=no difficulty and 3=inability to perform a task in that area). Overall score is computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

The ACR 50 Response is defined as greater than or equal to (\>=) 50 percent improvement in swollen joint count (66 joints) and tender joint count (68 joints) and \>=50 percent improvement in 3 of following 5 assessments: participant's assessment of pain using Visual Analog Scale (VAS; 0-10 millimeter \[mm\], 0 mm=no pain and 10 mm=worst possible pain), participant's global assessment of disease activity by using VAS (scale ranges from 0 mm to 100 mm, \[0 mm=no pain to 100 mm=worst possible pain\]), physician's global assessment of disease activity using VAS, participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI, defined as a 20-question instrument assessing 8 functional areas. The derived HAQ-DI ranges from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area) and C-reactive protein (CRP).

The SF-36 is a generic health survey with 36 items that measure functional health and well-being from the participant's perspective. The survey is summarized into 8 dimensions/scales: physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH). The physical component summary measure is derived from 4 of the 8 health dimensions (aggregate of PF, RP, BP, and GH scales). The minimum score is 0 and the maximum score is 100. A higher score indicates a better health state.

PASI 100 response is defined as 100% improvement in PASI score from baseline (PASI score of 0). The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI scoring 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%-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 higher score indicates more severe disease.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent	NCT04936308	Arthritis, Psor...	Guselkumab Placebo	18 Years -	Janssen Research & Development, LLC
Characterization of Immunogenicity of TNF Inhibitors in Arthritis Patients With Poorer Treatment Response.	NCT04731831	Arthritis, Rheu... Arthritis, Psor... Spondylitis, An...		18 Years -	Aalborg University Hospital
Guselkumab in Active Psoriatic Arthritis Participants With Inadequate Response/Intolerance to One Prior Anti-TNF Alpha Agent	NCT04936308	Arthritis, Psor...	Guselkumab Placebo	18 Years -	Janssen Research & Development, LLC
A Study of Guselkumab in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNF Alpha) Therapy	NCT03796858	Arthritis, Psor...	Guselkumab 100 ... Placebo	18 Years -	Janssen Pharmaceutica N.V., Belgium
A Study of Guselkumab in Participants With Active Psoriatic Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Alpha (Anti-TNF Alpha) Therapy	NCT03796858	Arthritis, Psor...	Guselkumab 100 ... Placebo	18 Years -	Janssen Pharmaceutica N.V., Belgium

Spots Global Cancer Trial Database for arthritis, psoriatic