Deucravacitinib-TNF Combination Therapy for Difficult-to-Control Psoriatic Disease (COMBo)

The University of Texas System (UT)

Status and phase: Not yet enrolling; Phase 4

Conditions: Psoriatic Arthritis (PsA)

Treatments: Drug: Placebo; Drug: Deucravacitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT07280702

STU-2025-0977

Details and patient eligibility

About

The purpose of this research study is to determine the effectiveness of adding deucravacitinib to the participant's current Psoriatic Arthritis (PsA) treatment to see if it improves their symptoms and quality of life.

This study is exploring a new treatment approach that may help improve control of psoriatic disease by targeting different parts of the disease process. By combining therapies that work together, the goal is to offer better symptom relief with fewer or more manageable side effects than some current treatments.

Enrollment: 128 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults aged 18-65 with confirmed psoriatic arthritis based on CASPAR criteria.

  • Ability to provide informed consent and comply with study procedures.

  • Patients with plaque psoriasis BSA>3% OR PsA with [SJC>2 AND TJC >3] despite stable background anti-TNF therapy for at least 6 months, with or without csDMARDs (i.e MTX, leflunomide, sulfasalazine, hydroxychloroquine).

  • Concurrent use of 1 csDMARD, and/or NSAID, and/or oral glucocorticoid is permitted but not required during the study. If such treatment was administered, then participants must meet the following requirements:

    • If on csDMARD (methotrexate [MTX], sulfasalazine [SSZ], leflunomide [LEF], hydroxychloroquine [HCQ]), the participant must have been on it for at least 12 weeks and be on a stable dose for at least 28 days prior to Day 1.

      • If on MTX, the route of administration and dose must be stable and the dose must be ≤ 25 mg/week.
      • If on SSZ, the dose must be ≤ 3 g/day.
      • If on HCQ, the dose must be ≤ 400 mg/day.
      • If on LEF, the dose must be ≤ 20 mg/day. Note: If currently not on MTX, SSZ, or HCQ, the participant must not have received it for at least 28 days prior to Day 1. If currently not on LEF, the participant must not have received it for at least 12 weeks prior to Day 1.

    • If on an NSAID, the participant must be on a stable dose for at least 14 days prior to Day 1.

    • Stable background use of prednisone 15 mg daily or equivalent is permitted. If on oral glucocorticoids, the participant must be on a stable dose of ≤ 15 mg/day prednisone equivalent for at least 28 days prior to Day 1.

    • Note: If currently not on oral glucocorticoids, the participant must not have received oral glucocorticoids within 28 days prior to Day 1

Exclusion criteria

• History of failure of more than two anti-TNF therapies, prior history of failure of TYK2 and JAK inhibitors.

  • History of prior allergic reaction or intolerance to deucravacitinib.

  • History of primary failure of anti-IL17, anti-IL23 is excluded. Note that prior exposure to these agents is allowed for reasons other than primary failure, eg intolerance, insurance / access issues, etc).

    • Systemic agents other than anti-TNF or csDMARD (ie. MTX, leflunomide, sulfasalazine, hydroxychloroquine) must have ceased > 6 months prior to baseline.
    • Doses or glucocorticoids >15mg daily prednisone or equivalent.

  • Severe cardiovascular, hepatic, or renal impairment.

  • History or evidence of outpatient active infection and/or febrile illness within 14 days prior to Day 1.

  • History of serious bacterial, fungal, or viral infection requiring hospitalization or parenteral antimicrobial treatment (eg, antibiotics antiviral, antifungal, or antiparasitic agents) within 60 days prior to Day 1.

  • Receipt of any therapy for chronic infection (eg, pneumocystis, herpes zoster, cytomegalovirus, invasive bacterial or fungal infections, or atypical mycobacteria) at screening.

  • Recent herpes zoster or herpes simplex infection or history of serious herpes zoster or herpes simplex infection defined as:

  • a) Herpes zoster or herpes simplex lesions within 30 days prior to randomization, OR

  • b) History of serious herpes zoster or serious herpes simplex infection, which includes, but it is not limited to, any episode of disseminated herpes simplex, multi- dermatomal herpes zoster, herpes encephalitis, ophthalmologic herpes, and/or recurrent herpes zoster (recurrent herpes zoster is defined as more than 2 episodes in the last 2 years).

  • Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the participant's immune status (eg, history of opportunistic infections [eg, Pneumocystis jirovecii pneumonia, histoplasmosis, or coccidioidomycosis], history of splenectomy, primary immunodeficiency).

  • Receipt of any live vaccine within 60 days prior to Day 1 or plans to receive a live vaccine during the study or within 60 days after completing study treatment.

  • Evidence of, or positive testing for, hepatitis B virus or hepatitis C virus at screening.

  • Positive testing for human immunodeficiency virus 1 or 2 by antibody testing at screening.

  • History of active TB prior to the screening visit, signs or symptoms of active TB at screening, positive QuantiFERON®-TB Gold (or equivalent) test result or 2 successive indeterminate QuantiFERON®-TB Gold (or equivalent) test results at screening.

  • History of chronic or recurrent infectious disease.

  • History of VTE, MACE, active solid malignancy or history of malignancy <5 years, any hematologic malignancy; history of multiple serious infections requiring hospitalization in the past 5 years, history of opportunistic infection, any condition which in the opinion of the investigator would pose a safety risk or inability to assess key endpoints in the study.

  • History of fibromyalgia/central sensitization, or other joint disease which in the opinion of the investigator would make musculoskeletal disease activity assessment challenging in the context of this study.

  • History of other inflammatory dermatosis which in the opinion of the investigator would make skin disease activity assessment challenging in the context of this study (eg atopic, contact dermatitis, etc).

  • Exclude use of topicals except for mild to mid-potency topical steroids for use only in cosmetically sensitive areas such as the face.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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128 participants in 2 patient groups, including a placebo group

established standard of care anti-TNF plus deucravacitinib

Experimental group

Description:

Deucravacitinib will be administered in tablet form. Anti-TNF will be administered by injection.

Treatment:

Drug: Deucravacitinib

established standard of care anti-TNF plus placebo

Placebo Comparator group

Description:

Placebo will be administered in tablet form. Anti-TNF will be administered by injection.

Treatment:

Drug: Placebo