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.

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

Arthritis, Psoriatic

Psoriatic Arthritis

Rheumatology

Immune system conditions

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.

Placebo

Guselkumab

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

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= no difficulty, 3= inability to perform task in that area), and CRP.

A psoriasis IGA response was defined as an IGA score of 0 (cleared) or 1 (minimal) and greater than equal to (>=2) grade reduction from baseline in the IGA psoriasis score. The IGA documents the investigator's assessment of the patient's 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 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).

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 was 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 severtiy. 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.

The HAQ-DI is a 20-question instrument that assesses the degree of difficulty a participant has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living), each scored from 0 (no difficulty) to 3 (inability to perform a task in that area). Overall score was 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. 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 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. A positive change indicates improvement while a negative change indicates worsening of health status and quality of life.

The FACIT-Fatigue 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 was 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 were reverse scored when appropriate to provide a scale in which higher scores represent better functioning or less fatigue.

MDA is 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, Psoriasis activity and severity index <=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 index score <= 1).

ACR 50 response: >=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 Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP.

ACR 70 response: >=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 Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP.

Serum concentrations of guselkumab over time was reported.

Number of participants with antibodies to guselkumab (ADA) were reported. A validated immunoassay was used to detect ADA.

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.

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.

Rheumatology Associates

Arizona Arthritis and Rheumatology Research, PLLC

Arizona Arthritis & Rheumatology Associates

Southern Arizona VA Healthcare System

Unity Health-White County Medical Center

Newport Huntington Medical Group

Medvin Clinical Research

Clinical Research Center of Connecticut

Bay Pines VA Healthcare System

Clinical Research of West Florida

Omega Research Consultants

Advanced Clinical Research of Orlando

Integral Rheumatology & Immunology Specialists

Florida Medical Clinic, P.A.

Great Lakes Clinical Trials

Clinic of Robert Hozman

The Arthritis and Diabetes Clinic

Johns Hopkins University

Klein & Associates, M.D., P.A.

Great Lakes Center of Rheumatology

Arthritis and Rheumatology Center of MI

Clinical Research Institute of Michigan, LLC

St. Paul Rhuematology, P.A.

Arthritis Consultants

Arthritis Rheumatic And Back Disease Associates

Albuquerque Center for Rheumatology

Arthritis and Osteoperosis Associates of New Mexico

Buffalo Rheumatology and Medicine PLLC

DJL Clinical Research, PLLC

STAT Research, Inc.

Health Research of Oklahoma

Dr. Ramesh Gupta

Precision Comprehensive Clinical Research Solutions

Adriana Pop Moody MD Clinic PA

Metroplex Clinical Research Center

West Texas Clinical Research

Southwest Rheumatology Research LLC

Texas Rheumatology Care

Advanced Rheumatology of Houston

DM Clinical Research

Arthritis & Osteoporosis Clinic

Arthritis Northwest PLLC

Rheumatology & Pulmonary Clinic

Cosultorios Reumatologógicos Pampa

Centro Privado de Medicina Familiar

Hospital Central Militar Cirujano Mayor Dr Cosme Argerich

CIPREC

Instituto de Reumatología Mendoza

Centro de Investigaciones Medicas Tucuman

Southern Clinical Research

Liverpool Hospital

Skin Health Institute Inc.

Eastern Health - Box Hill Hospital

UMHAT 'Dr. Georgi Stranski', EAD

Medical Center Unimed Plovdiv

UMHAT Kaspela

Diagnosis-consulting centre-1

UMHAT St. Ivan Rilski

Military Medical Academy

ASIMP Rheumatology Centre "St Irina" EOOD

University Multiprofile Hospital Sofiamed Sofia

Medical Centre Synexus

RHEUMA s.r.o.

L.K.N Arthrocentrum

MUDr. Rosypalova, s.r.o

Arthrohelp S.R.O.

Revmatologicky ustav

Medical Plus S.R.O.

PV-Medical S.R.O

Betegapolo Irgalmas Rend - Budai Irgalmasrendi Korhaz

Uno Medical Trials Ltd.

Debreceni Egyetem, Kenézy Gyula Egyetemi Oktatókórház

Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaz

Pest Megyei Flor Ferenc Korhaz

Szegedi Tudományegyetem, ÁOK, Szent-Györgyi Albert Klinikai Központ

Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz

Vital Medical Center Orvosi es Fogaszati Kozpont

Bnai Zion Medical Center

Rambam Health Care Campus

Carmel Medical Center

Meir Medical Center

Sheba Medical Center

Hospital Selayang

Hospital Pulau Pinang

Hospital Raja Permaisuri Bainun

Hospital Tuanku Jaafar

Nzoz Bif-Med

Centrum Kliniczno Badawcze

Malopolskie Badania Kliniczne Sp. z o.o.

Malopolskie Centrum Kliniczne

Centrum Medyczne Promed

Dermed Centrum Medyczne Sp. z o.o

Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo-Akcyjna

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.

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures