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A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti -Tumor Necrosis Factor (TNF) Alpha Agent(s) (Discover-1)

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ClinicalTrials.gov Identifier: NCT03162796
Recruitment Status : Active, not recruiting
First Posted : May 22, 2017
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The primary purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active Psoriatic Arthritis (PsA) by assessing the reduction in signs and symptoms of PsA.

Condition or disease Intervention/treatment Phase
Arthritis, Psoriatic Drug: Guselkumab Drug: Placebo Phase 3

Detailed Description:
This is a study of guselkumab in participants with active Psoriatic Arthritis (PsA) who had inadequate response to standard therapies. It will evaluate the clinical efficacy of guselkumab in the reduction of signs and symptoms and the safety profile of guselkumab in the treatment of PsA. The study will consists of 4 phases: a screening phase of up to 6 weeks, a blinded treatment phase of approximately 1 year (that is, 52 weeks), including a placebo controlled period from Week 0 to Week 24 and double-blind active treatment period from Week 24 to Week 52, and a safety follow-up phase of 8 weeks after Week 52 (Week 52 to 60) and will be 12 weeks from the last administration of study agent (at Week 48) to the final safety follow-up visit. Efficacy, safety, pharmacokinetic, immunogenicity, and biomarker evaluations will be performed in the study at defined schedule.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 383 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti-TNF Alpha Agents
Actual Study Start Date : August 24, 2017
Estimated Primary Completion Date : October 11, 2019
Estimated Study Completion Date : November 21, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Guselkumab

Arm Intervention/treatment
Experimental: Group 1: Guselkumab
Participants will receive subcutaneous (SC) guselkumab 100 milligram (mg) once every 4 weeks (q4w) from Week 0 through Week 48.
Drug: Guselkumab
Participants will receive 100mg of guselkumab as a sterile liquid for SC injection.
Other Name: CNTO 1959

Experimental: Group 2: Guselkumab and Placebo
Participants will receive SC guselkumab 100 mg at Weeks 0 and 4, then once every 8 weeks (q8w) (Weeks 12, 20, 28, 36, and 44) and placebo injections at other visits (Weeks 8, 16, 24, 32, 40, 48) to maintain the blind.
Drug: Guselkumab
Participants will receive 100mg of guselkumab as a sterile liquid for SC injection.
Other Name: CNTO 1959

Drug: Placebo
Participants will receive matching placebo as SC injection.

Experimental: Group 3: Placebo Followed by Guselkumab
Participants will receive SC placebo q4w from Week 0 to Week 20, and will crossover at Week 24 to receive guselkumab 100 mg q4w from Week 24 through Week 48.
Drug: Guselkumab
Participants will receive 100mg of guselkumab as a sterile liquid for SC injection.
Other Name: CNTO 1959

Drug: Placebo
Participants will receive matching placebo as SC injection.




Primary Outcome Measures :
  1. Percentage of Participants who Achieve an American College of Rheumatology (ACR) 20 Response at Week 24 [ Time Frame: Week 24 ]
    ACR 20 Response is defined as greater than or equal to (>=) 20 percent improvement from baseline in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement from baseline in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10, 0 = no pain and 10 = worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, 0=very well and 10=very poor), physician's global assessment of disease activity using VAS (0=no arthritis activity and 10 = 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. The 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).


Secondary Outcome Measures :
  1. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24 [ Time Frame: Baseline and Week 24 ]
    The Health Assessment Questionnaire-Disability Index (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).

  2. Percentage of Participants who Achieve an ACR 50 Response at Week 24 [ Time Frame: Week 24 ]
    ACR 50 Response is defined as >= 50 percent improvement from baseline in swollen joint count (66 joints) and tender joint count (68 joints) and >=50 percent improvement from baseline in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10, 0 = no pain and 10 = worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, 0=very well and 10=very poor), physician's global assessment of disease activity using VAS (0=no arthritis activity and 10 = 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. The 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).

  3. Percentage of Participants With a Psoriasis Response of IGA (Score of 0 [Cleared] or 1 [Minimal]) at Week 24 Among the Participants With >=3% (percentage) Body Surface Area (BSA) Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline [ Time Frame: Week 24 ]
    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 of Psoriasis documents the investigator's assessment of the participant's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling using 0 (no evidence), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe) scale. The IGA score of psoriasis is based upon the average of induration, erythema and scaling scores. The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4).

  4. Percentage of Participants who Achieve an ACR 20 Response at Week 16 [ Time Frame: Week 16 ]
    ACR 20 Response is defined as >= 20 percent improvement from baseline in swollen joint count (66 joints) and tender joint count (68 joints) and >=20 percent improvement from baseline in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10, 0 = no pain and 10 = worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, 0=very well and 10=very poor), physician's global assessment of disease activity using VAS (0=no arthritis activity and 10 = 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. The 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).

  5. Change From Baseline in Disease Activity Score (DAS28) (C-reactive Protein [CRP]) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The Disease Activity Index Score (DAS28) based on C-Reactive Protein (CRP) is an index combining tender joints (28 joints), swollen joints (28 joints), CRP and patient's global assessment of disease activity. The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. DAS28(CRP) =0.56×SQRT(tender joints [count:1-28])+0.28×SQRT(swollen joints [count:1-28])+0.36×Ln(CRP value in milligram per Litre [mg/L] +1)+0.014×GH (patient's global assessment of disease activity by using VAS of 100 mm scale [100=most severe])+0.96. Higher score = more severe disease.

  6. Percentage of Participants who Achieve an ACR 70 Response at Week 24 [ Time Frame: Week 24 ]
    ACR 70 Response is defined as >= 70 percent improvement from baseline in swollen joint count (66 joints) and tender joint count (68 joints) and >=70 percent improvement from baseline in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10, 0 = no pain and 10 = worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, 0=very well and 10=very poor), physician's global assessment of disease activity using VAS (0=no arthritis activity and 10 = 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. The 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).

  7. Percentage of Participants who Achieve an ACR 50 Response at Week 16 [ Time Frame: Week 16 ]
    ACR 50 Response is defined as >= 50 percent improvement from baseline in swollen joint count (66 joints) and tender joint count (68 joints) and >=50 percent improvement from baseline in 3 of following 5 assessments: patient's assessment of pain using Visual Analog Scale (VAS; 0-10, 0 = no pain and 10 = worst possible pain), patient's global assessment of disease activity by using VAS (the scale ranges from 0 to 10, 0=very well and 10=very poor), physician's global assessment of disease activity using VAS (0=no arthritis activity and 10 = 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. The 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).

  8. Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) at Week 24 [ Time Frame: Baseline and Week 24 ]
    SF-36 is a survey of participant health. It consists of 8 individual domains, which are weighted sums of the questions in their section. The 8 domains are: vitality (VT), physical functioning (PF), bodily pain (BP), general health (GH), Role-Physical (RP), Role-Emotional (RE), social functioning (SF) and mental health (MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on the scale scores, the summary physical component score (PCS) is derived. Scales contributing most to the scoring of the SF-36 PCS include the PF, RP, BP and GH. Other domains not noted contribute to the scoring but to a lesser degree. The scoring is derived based on an algorithm that has been developed in a software provided by the developer. The summary PCS score is also scaled from 0 to 100 with higher scores indicating better health.

  9. Percentage of Participants With Resolution of Enthesitis at Week 24 Among the Participants With Enthesitis at Baseline [ Time Frame: Week 24 ]
    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 or absence of pain by applying local pressure to Lateral epicondyle humerus, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. Leeds Enthesitis Index scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

  10. Change From Baseline in Enthesitis Score (Based on Leeds Enthesitis Index [LEI]) at Week 24 Among the Participants with Enthesitis at Baseline [ Time Frame: Baseline and Week 24 ]
    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 or absence of pain by applying local pressure to Lateral epicondyle humerus, left and right, Medial femoral condyle, left and right, and Achilles tendon insertion, left and right. Leeds Enthesitis Index scores ranging from 0 (0 sites with tenderness) to 6 (worst possible score; 6 sites with tenderness).

  11. Change From Baseline in SF-36 Mental Component Summary (MCS) at Week 24 [ Time Frame: Baseline and Week 24 ]
    The SF-36 is a survey of participant health. It consists of 8 individual domains, which are weighted sums of the questions in their section. The 8 domains are: vitality (VT), physical functioning (PF), bodily pain (BP), general health (GH), Role-Physical (RP), Role-Emotional (RE), social functioning (SF) and mental health (MH). Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better health. Based on the scale scores, the summary mental component score (MCS) is derived. Scales contributing most to the scoring of the SF-36 MCS include the VT, SF, RE and MH. Other domains not noted contribute to the scoring but to a lesser degree. The scoring is derived based on an algorithm that has been developed in a software provided by the developer. The summary MCS score is also scaled from 0 to 100 with higher scores indicating better health.

  12. Percentage of Participants With Resolution of Dactylitis at Week 24 Among the Participants with Dactylitis at Baseline [ Time Frame: Week 24 ]
    The presence and severity of dactylitis will be assessed in both hands and feet using a scoring system from 0 to 3 (0 = no dactylitis, 1 = mild dactylitis, 2 = moderate dactylitis, and 3 = severe dactylitis). Resolution is defined as a score of 0. This analysis is for the sub-population of score greater than (>) 0 at baseline.

  13. Change From Baseline in Dactylitis Scores at Week 24 Among the Participants with Dactylitis at Baseline [ Time Frame: Baseline and Week 24 ]
    The presence and severity of dactylitis will be assessed in both hands and feet using a scoring system from 0 to 3 (0 = no dactylitis, 1 = mild dactylitis, 2 = moderate dactylitis, and 3 = severe dactylitis).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a diagnosis of Psoriatic Arthritis (PsA) for at least 6 months before the first administration of study agent and meet Classification criteria for Psoriatic Arthritis (CASPAR) at screening
  • Have active PsA as defined by: at least 3 swollen joints and at least 3 tender joints at screening and at baseline; and C-reactive protein (CRP) greater than or equal to (>=) 0.3 milligram per deciLitre (mg/dL) at screening from the central laboratory
  • Have 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
  • Have active plaque psoriasis, with at least one psoriatic plaque of >= 2 centimeter (cm) diameter or nail changes consistent with psoriasis or documented history of plaque psoriasis
  • Have active PsA despite previous non-biologic disease-modifying antirheumatic drugs (DMARD), apremilast, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy : Non-biologic DMARD therapy is defined as taking a non-biologic DMARD for at least 3 months or evidence of intolerance; Apremilast therapy is defined as taking apremilast at the marketed dose approved in the country where the study is being conducted for at least 4 months or evidence of intolerance; NSAID therapy is defined as taking an NSAID for at least 4 weeks or evidence of intolerance
  • Participants may have been previously treated with up to 2 anti-TNF (tumor necrosis factor) alpha agents (approximately 30 percent [%] of the overall study population), and must document the reason for discontinuation

Exclusion Criteria:

  • Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, or Lyme disease
  • Has ever received more than 2 anti-TNFalpha agents
  • Has previously received any biologic treatment (other than anti-TNF alpha agents), including, but not limited to ustekinumab, abatacept, secukinumab, tildrakizumab, ixekizumab, brodalumab, risankizumab, or other investigative biologic treatment
  • Has previously received any systemic immunosuppressants (for example, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study agent
  • Has received apremilast within 4 weeks prior to the first administration of study agent
  • Has previously received tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K), decernotinib (VX‑509), or any other Janus kinase (JAK) inhibitor

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03162796


  Show 95 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03162796     History of Changes
Other Study ID Numbers: CR108218
2016-001163-37 ( EudraCT Number )
CNTO1959PSA3001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: May 22, 2017    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Arthritis
Arthritis, Psoriatic
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases