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

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 4
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 80
Healthy Volunteers: f
View:

• 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;

• Are willing to refrain from the use of complementary therapies for PsA or psoriasis including ayurvedic medicine, traditional Taiwanese, Korean, or Chinese medications, and acupuncture within 2 weeks before the first study agent administration and through Week 52;

• Signed informed consent.

Locations
Other Locations
Italy
Immunorheumatology Unit, Fondazione Policlinico Universitario Campus Bio-Medico
RECRUITING
Rome
Contact Information
Primary
Luca Navarini, MD
l.navarini@policlinicocampus.it
+3906225411779
Backup
Francesca Scintu, Biologist
f.scintu@policlinicocampus.it
+3906225411779
Time Frame
Start Date: 2024-06-18
Estimated Completion Date: 2027-05-27
Participants
Target number of participants: 26
Treatments
Other: Psoriatic Arthritis
Patients with Psoriatic Arthritis undergoing Guselkumab treatment
Sponsors
Leads: Fondazione Policlinico Universitario Campus Bio-Medico

This content was sourced from clinicaltrials.gov