Spondyloarthritis: Inducing Drug-free Remission by Early TNF-alpha Blockade

• Status: Recruiting
• Trial end date: 2026-05-31
• Target enrollment: 0
• Participant gender: All

Summary

The SPARTACUS study will explore the therapeutic efficacy of 2 different treatment strategies for patients suffering from peripheral Spondyloarthritis (pSpA), classified according to the "Assessment in SpondyloArthritis international Society" (ASAS) classification criteria; it will be set up as a 48-week, prospective, randomized, active-comparator controlled, double-blind, double-dummy, clinical trial with a two-fold clinical objective:

• To compare a standard step-up approach using conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs), such as methotrexate and/or sulphasalazine (the "csDMARD Step-Up"-strategy), with an early remission-induction treatment strategy that immediately introduces biological DMARDs (bDMARDs) as the first step in the treatment algorithm; in this group the Tumor Necrosis Factor inhibitor (TNFi) golimumab will be utilised (the "TNFi Induction"-strategy).

• To define the window of opportunity within which temporary treatment with bDMARDs might be more effective, by stratifying patients according to symptom duration: patients with shorter symptom duration (<3 months) versus those with more longstanding disease (between 3-12 months of symptom duration).

The double-blind phase of the study will compare the 2 treatment strategies with regard to the proportion of patients that achieve a status of (sustained) clinical remission. Differences between patients with very early disease (<3 months symptom duration) versus those with symptom duration between 3 and 12 months, will be evaluated.

In patients that reach sustained clinical remission, all study treatments (both in the "csDMARD Step-up"-group and the "TNFi Induction"-group) will be stopped, and long-term, clinical follow-up of these patients will allow to explore the possibility of "drug-free remission"; also with regard to this objective, the difference in symptom duration will be evaluated.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Ghent
• Collaborators: Merck Sharp & Dohme Corp.; Vlaams Instituut voor Biotechnologie (VIB); Merck Sharp & Dohme (MSD)

Criteria

Inclusion Criteria:

SPARTACUS Phase A: "Remission-Induction Phase"

A subject will be eligible for study participation if all of the following criteria are met:

• Subjects must be able and willing to provide written informed consent and comply with the requirements of this study protocol.

• Subjects must be between 18 and 65 years of age.

• Subjects must have been diagnosed with peripheral spondyloarthritis by the treating rheumatologist.

• Subjects must meet the ASAS classification criteria for peripheral spondyloarthritis:

subjects must have current arthritis (asymmetric or predominantly in the lower limbs) or current enthesitis (except for enthesitis only along the spine, sacroiliac joints and/or chest wall) or current dactylitis plus at least 1 of the following SpA features:

• Anterior uveitis confirmed by an ophthalmologist (past or present)

• Crohn's disease or ulcerative colitis diagnosed by a gastroenterologist (past or present).

• Evidence of preceding infection (acute diarrhea or non-gonococcal urethritis or cervicitis 1 month before arthritis).

• Psoriasis diagnosed by a dermatologist (past or present).

• HLA B27 positivity

• Sacroiliitis by imaging defined as bilateral grade 2-4 or unilateral grade 3-4 sacroiliitis on plain radiographs, according to the modified New York criteria or active sacroiliitis on MRI according to the ASAS consensus definition (ref of addendum).

• Subjects must have had onset of peripheral SpA symptoms ≤12 months prior to the screening visit.

• Subjects must have active disease at screening defined by Patient Global Assessment of Disease Activity Numerical Rating Scale (NRS) ≥ 4 and Patient Global Assessment of Pain NRS ≥ 4. At the baseline visit patients will be clinically evaluated to exclude spontaneous clinical remission.

• In subjects with concurrent axial SpA symptoms, the peripheral SpA symptoms must be the predominant symptoms at study entry based on the Investigator's clinical judgment.

• Subjects must have a negative PPD test (or equivalent) and chest radiography (anteroposterior and lateral view) at screening. If the subject has a positive PPD test (or equivalent), has had a past ulcerative reaction following PPD placement and/or a chest radiography consistent with prior TB exposure, the subject must initiate, or have documented completion of a course of anti-TB therapy.

• Women of childbearing potential or men capable of fathering children must be using adequate birth control measures during the study and for 3 months after receiving the last administration of study agent.

• Subject is judged to be in good health as determined by the principal investigator based upon the results of medical history, physical examination, laboratory profile, and chest x-ray (CXR) performed during screening.

• Subjects must be able and willing to self-administer SC injections or have a qualified person available to administer SC injections.

SPARTACUS Phase B: "Drug-Free Remission Phase"

A subject will be eligible for phase B of the study if all of the following criteria are met:

• Subjects must have participated in SPARTACUS Phase A.

• Subjects must have reached a status of sustained clinical remission (defined as absence of clinical arthritis, enthesitis and dactylitis at 2 consecutive 'major' visits with an interval of 12 weeks).

Exclusion Criteria:

• Medical history of inflammatory arthritis of a different etiology than peripheral spondyloarthritis (e.g. rheumatoid arthritis, systemic lupus erythematosus, gout, …).

• Prior adequate treatment with methotrexate and/or sulphasalazine.

• Prior exposure to any biologic therapy with a potential therapeutic impact on SpA.

• Treatment with any investigational drug of chemical or biological nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to the Baseline Visit.

• Subject is taking or has taken prohibited medications as outlined in Table 1 without meeting the mandatory washout period(s) relative to the baseline visit.

• Infection(s) requiring treatment with intravenous (iv) anti-infective agents within 30 days prior to the Baseline visit or oral anti-infectives within 14 days prior to the baseline Visit.

• Have a known hypersensitivity to human immunoglobulin proteins or other components of golimumab.

• History of central nervous system (CNS) demyelinating disease or neurologic symptoms suggestive of CNS demyelinating disease.

• History of listeriosis, histoplasmosis, chronic or active Hepatitis B infection, Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active TB.

• (History of) chronic heart failure, including medically controlled, asymptomatic CHF.

• History of malignancy (including lymphoma and leukemia) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.

• Have received any live virus or bacterial vaccination within 3 months prior to the first administration of study agent; patients who are expected to receive such vaccinations during the trial, or within 3 months after the last administration of study agent.

• Positive serum pregnancy test at screening.

• Female subjects who are breast-feeding.

• Clinically significant abnormal screening laboratory results as evaluated by the Investigator.

• Positive anti-cyclic citrullinated peptide (anti-CCP) antibody at screening if the titers are crossing 3 times the upper limit of normal.

• Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

• Subject with current symptoms of fibromyalgia that would confound evaluation of the patient.