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

NCT04435288 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: BC-06226
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Peripheral Spondyloarthritis

Outcome Measures

Primary Outcomes (1)

• Clinical remission

  At week 24 of the study the 2 treatment strategies will be compared with regard to achievement of clinical remission. Clinical remission is defined as complete absence of arthritis, dactylitis or enthesitis on clinical examination.

  24 weeks

Study Arms (2)

TNFi-induction group

ACTIVE COMPARATOR

The patients in the TNFi-induction group will receive golimumab at a standard dose of 50 mg subcutaneously (SC) every 4 weeks (with matching methotrexate (MTX)-placebo). In case of potential intolerance or toxicity to MTX-placebo, the dose will be gradually tapered to a minimum of 7.5 mg per week. When there are no tolerability/toxicity issues, the weekly dose of MTX-placebo will be increased to 20 mg at week 4. At week 12, a "Patient Acceptable Signs \& Symptoms Improvement" ('PASSI') will be assessed by asking the question "Taking into account both efficacy and side effects, did you experience over the past 12 weeks enough improvement in signs and symptoms of your' arthritis-enthesitis-dactylitis to consider continuation of the same treatment schedule for the next 12 weeks?". If yes, all study medication will be kept stable until week 24; if no, oral sulphasalazine at a dose of 2 g per day will be started (escape medication).

Drug: week 24; Drug: week 36; Drug: Week 48; Drug: Week 60

csDMARD-Step-up group

ACTIVE COMPARATOR

The patients in the csDMARD-Step-up group will start with oral methotrexate (MTX) at a weekly dose of 15 mg for 4 weeks (with matching TNFi-placebo injections). In case of potential intolerance or toxicity to MTX , the dose will be gradually tapered to a minimum of 7.5 mg per week. When there are no tolerability/toxicity issues, the weekly dose of MTX will be increased to 20 mg at week 4. At week 12, a "Patient Acceptable Signs \& Symptoms Improvement" ('PASSI') will be assessed by asking the question "Taking into account both efficacy and side effects, did you experience over the past 12 weeks enough improvement in signs and symptoms of your' arthritis-enthesitis-dactylitis to consider continuation of the same treatment schedule for the next 12 weeks?". If yes, all study medication will be kept stable until week 24; if no, oral sulphasalazine at a dose of 2 g per day will be started (escape medication).

Drug: week 24; Drug: week 36; Drug: Week 48; Drug: Week 60

Interventions

week 24 DRUG

At the week 24 timepoint, there are 3 possible scenario's: 1. In patients that do not reach a state of clinical remission at week 24, blinded study medication will be interrupted and all patients will start open-label SC golimumab for an additional 36 weeks (up to max. week 60). 2. In patients that achieve sustained clinical remission at week 24, defined as absence of clinical arthritis, enthesitis and dactylitis at both week 12 and week 24, all study medication will be discontinued and prospective follow-up will be planned in SPARTACUS Phase B. 3. In patients that reach a state of clinical remission at week 24, but that did not yet reach this status at week 12, blinded study medication will be continued without any change in the treatment schedule for another 12 weeks.

TNFi-induction group; csDMARD-Step-up group

week 36 DRUG

At week 36, patients that have continued the blinded study medication, will be re-assessed regarding sustained clinical remission (at week 24 and 36): if yes, all study medication will again be discontinued and prospective follow-up will be planned in SPARTACUS Phase B. If no, these patients will start open-label SC golimumab for an additional 24 weeks (up to max. week 60). If patients were in the "open-label golimumab treatment arm", effectiveness of the treatment will be assessed by using the "PASSI"-question. Inadequate responders will be discontinued from the study and will be treated with standard-of-care medication at the discretion of their treating rheumatologist, whereas patients with an acceptable improvement in signs and symptoms will continue with the same (open-label) medication schedule.

TNFi-induction group; csDMARD-Step-up group

Week 48 DRUG

At week 48, all patients still remaining in SPARTACUS Phase A will have been treated with open-label golimumab (for a minimum of 12 weeks, but potentially up to 48 weeks). In patients reaching at this timepoint sustained clinical remission (at week 36 and 48), golimumab will be discontinued and prospective follow-up will be planned in SPARTACUS Phase B. For the other patients there are 3 possible scenarios: 1. If clinical remission for the first time at week 48, continuation without any change in the treatment schedule for another 12 weeks. 2. If an inadequate response (based on the "PASSI"-question), discontinuation from the study and standard-of-care medication 3. If an acceptable improvement (but no clinical remission), continuation open-label golimumab for an additional 12 weeks, with open-label methotrexate (unless contra-indicated) to fulfil Belgian reimbursement criteria for TNFi.

TNFi-induction group; csDMARD-Step-up group

Week 60 DRUG

At week 60 (final study visit of SPARTACUS Phase A), patients reaching sustained clinical remission (at week 48 and 60), will roll-over into SPARTACUS Phase B. All other patients will be discontinued and will be treated with standard-of-care medication (including TNFi, if in accordance with Belgian reimbursement criteria).

TNFi-induction group; csDMARD-Step-up group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Ghent: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (6)

ASZ Aalst

Aalst, 9300, Belgium

Location

AZ Sint-Jan

Bruges, 8000, Belgium

Location

AZ Maria Middelares

Ghent, 9000, Belgium

Location

UZ Ghent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

ZNA Jan Palfijn

Merksem, 2170, Belgium

Location

Study Officials

• Dirk Elewaut, Prof. dr

  UZ Ghent

  PRINCIPAL INVESTIGATOR

• Filip Van den Bosch, Prof. dr

  UZ Ghent

  PRINCIPAL INVESTIGATOR

• Philippe Carron, Dr.

  Uz Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The SPARTACUS clinical trial consists of 2 phases (duration phase A is up to 60 weeks, phase B up to 3 years). SPARTACUS Phase A: "Remission-Induction Phase": (Baseline to (maximum) week 60) All patients (n=112) will be randomized (1:1) to either immediately receiving TNFi (golimumab) monotherapy ("TNFi Induction"-group) (n=56), or to the step-up regimen with csDMARDs ("csDMARD Step-up"-group) (n=56). SPARTACUS Phase B: "Drug-Free Remission Phase": cessation of therapy and exploration of drug-free remission in patients that achieve sustained clinical remission while on therapy in phase A (Duration: max. 3 years).

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 17, 2020
• Study Start: August 24, 2020
• Primary Completion: May 31, 2025
• Study Completion (Estimated): December 31, 2028
• Last Updated: September 26, 2025

Record last verified: 2025-09

Locations

BE (6)