Potential Role of Guselkumab in Modulating PAIN Perception and Related Gene Pathways: a Proof-of-concept Study.

NCT06974474 | Recruiting Phase 4 FDA Drug

• 1 other identifier: CNTO1959PSA4016
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Psoriatic arthritis (PsA) is a chronic musculoskeletal disease that affects 0.1%-1% of the general population and about 20% of patients with psoriasis. Patients with PsA have a multifaceted pain experience, which depends on various factors, including joint inflammation, as well as peripheral and central pain sensitization. Although chronic pain is the most common symptom of PsA, few is known about the mechanisms driving it. From this point of view, the interactions between immune cells and nociceptors in the context of inflammation-related pain are emerging as a hot topic. Many studies suggested that IL-23/IL-17 pathway may play a pivotal role in this regard. This is consistent with data currently available regarding Guselkumab in PsA. Indeed, according to DISCOVER 1 and DISCOVER 2, two randomized phase III trials, patients receiving Guselkumab achieved, among others, minimal disease activity state, significant improvement in the SF-36 physical component score, and visual analog scale of pain. This study proposal aims to evaluate the potential role of Guselkumab in modulating pain perception in PsA patients from a molecular, cellular, and electrophysiological point of view.

Conditions

Psoriasis Arthritis

Keywords

Guselkumab

Outcome Measures

Primary Outcomes (1)

• pain-related genes mRNA

  Change in synovial transcriptomic profiling of pain-related genes (as described by Perkins JR et al, Pain 2013; Bratus-Neuenschwander A et al, Genes 2018) in PsA patients before and after six months of treatments with Guselkumab.

  6 months

Study Arms (1)

Psoriatic Arthritis

OTHER

Patients with Psoriatic Arthritis undergoing Guselkumab treatment

Drug: Guselkumab

Interventions

Guselkumab DRUG

Guselkumab

Psoriatic Arthritis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A man or a woman at least 18 and no more than 80 years of age;
• Have a diagnosis of psoriatic arthritis (PsA) for at least 6 months the enrolment and meet Classification criteria for Psoriatic Arthritis (CASPAR) at screening;
• Inadequate response or intolerance of standard treatment (namely, methotrexate and/or TNF inhibitors);
• At least 3 months of non-biologic DMARDs (limited to methotrexate ≤25 mg/week, sulfasalazine ≤3 g/day, hydroxychloroquine ≤400 mg/day, and leflunomide ≤20mg/day) or at least 4 weeks of NSDAIDs for psoriatic arthritis;
• Patient eligible for Guselkumab (both monotherapy or combination therapy with methotrexate) treatment according to international recommendations, national and regional regulatory authorities, and EMA datasheet;
• VAS pain major than 15 mm at the enrolment;
• DAPSA major than 14 at the enrolment;
• Have at least 1 of the PsA subsets: oligoarticular or polyarticular PsA subset, distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, spondylitis with peripheral arthritis;
• Peripheral tender joints ≥ 1
• Peripheral swollen joints ≥ 1
• C-reactive protein ≥ 0.3 mg/dL
• Involvement (namely, swollen joint) of wrists or knees;
• Subjects naïve to bDMARDs or previously treated with up to 2 anti-tumor necrosis factor (TNFα) agents, discontinued for lack of benefit to an anti-TNFα therapy, as assessed by the treating physician, after at least 12 weeks of etanercept, adalimumab, golimumab, or certolizumab pegol therapy (or biosimilar) and/or at least a 14-week dosage regimen (i.e., at least 4 doses) of infliximab (or biosimilar). Documented lack of benefit may include inadequate improvement in joint counts, physical function, or disease activity; Intolerance to an anti-TNFα biologic therapy, as assessed by the treating physician, to etanercept, adalimumab, golimumab, certolizumab pegol, or infliximab (or biosimilars); If no intolerance or lack of benefit, the reason for discontinuation must be documented;
• If currently using non-biologic DMARDs (limited to methotrexate \[MTX\], sulfasalazine \[SSZ\], hydroxychloroquine \[HCQ\], or leflunomide \[LEF\]), subjects should have started treatment at least 3 months and the dose must be stable for at least 4 weeks before the first administration of study agent and should have no serious toxic side effects attributable to the non-biologic DMARD. If currently not using a MTX, SSZ, or HCQ, must have not received for at least 4 weeks before the first administration of study agent. If currently not using LEF, must not have received for at least 12 weeks before the first administration of study agent. If using MTX, the route of administration and dose must be stable and the dose must be ≤25 mg/week. If receiving SSZ, the dose must be ≤ 3g/day. If receiving HCQ, the dose must be ≤400 mg/day. If receiving LEF, the dose must be ≤20 mg/day.
• If currently using NSAIDs or other analgesics for PsA, subjects must be on a stable dose for at least 2 weeks before the first administration of study agent. If currently not using NSAIDs or other analgesics for PsA, must not have received NSAIDs or other analgesics for PsA within 2 weeks before the first administration of study agent;

You may not qualify if:

• Diagnosis of fibromyalgia according to ACR 2016 criteria;
• Subjects with inflammatory diseases that might confound the evaluations of benefit of Guselkumab therapy, including but not limited to RA, axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, or Lyme disease;
• Patients who received more than 2 anti-TNFα agents; - Has received an anti-TNF agent within the following timeframes: Infliximab (or its biosimilars) or golimumab (intravenous) within 8 weeks before the first administration Guselkumab; Golimumab (subcutaneous), adalimumab (or its biosimilars) or certolizumab pegol within 6 weeks before the first administration of study agent; Etanercept (or its biosimilars) within 4 weeks before the first administration of study agent;
• Has previously been treated with Guselkumab; - Diagnosis of psychiatric disorder according to DSM-V; - Pregnancy or lactation;
• Systemic or intra-articular glucocorticoids in the last 3 months;
• Has previously received any biologic treatment (other than anti-TNFα agents), including, but not limited to ustekinumab, abatacept, secukinumab, tildrakizumab, ixekizumab, brodalumab, risankizumab, or other investigative biologic treatment;
• Has previously received tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K), decernotinib (VX-509), or any other Janus kinase (JAK) inhibitor, as well as apremilast;
• Has previously received any systemic immunosuppressants (e.g., azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study agent;
• Has received non-biologic DMARDs (other than MTX, SSZ, HCQ, LEF) including, but not limited to chloroquine, gold preparations, and penicillamine within 4 weeks before the first administration of study agent;
• Is currently receiving 2 or more allowed non-biologic DMARDs at baseline;
• Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic (with the exception of PsA), genitourinary, or metabolic disturbances;
• Has unstable cardiovascular disease, defined as a recent clinical deterioration (e.g., unstable angina, rapid atrial fibrillation, or transient ischemic attack) in the last 3 months prior to screening or a cardiac hospitalization within the last 3 months prior to screening;
• Currently has a malignancy or has a history of malignancy within 5 years before screening (with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study agent administration or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first Guselkumab administration);
• Has a history of lymphoproliferative disease, including lymphoma; a history of monoclonal gammopathy of undetermined significance; or signs and symptoms suggestive of possible lymphoproliferative diseases, such as lymphadenopathy or splenomegaly;
• Has a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (e.g., bronchiectasis), recurrent urinary tract infection (e.g., recurrent pyelonephritis or chronic nonremitting cystitis), fungal infection (e.g., mucocutaneous candidiasis), or open, draining, or infected skin wounds or ulcers;

Sponsors & Collaborators

• Fondazione Policlinico Universitario Campus Bio-Medico: lead

Study Sites (1)

Immunorheumatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico

Rome, Italy, 00128, Italy

RECRUITING

MeSH Terms

Interventions

guselkumab

Central Study Contacts

Luca Navarini, MD

CONTACT

+3906225411779; l.navarini@policlinicocampus.it

Francesca Scintu, Biologist

CONTACT

+3906225411779; f.scintu@policlinicocampus.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2024
• First Posted: May 16, 2025
• Study Start: June 18, 2024
• Primary Completion: November 27, 2025
• Study Completion (Estimated): May 27, 2027
• Last Updated: May 16, 2025

Record last verified: 2024-05

Locations

IT (1)