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

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

Interventions

DRUG

week 24

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.

DRUG

week 36

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.

DRUG

Week 48

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.

DRUG

Week 60

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).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC

  collaborator INDUSTRY

• University Hospital, Ghent

  lead OTHER

Principal Investigators

• Dirk Elewaut, Prof. dr · UZ Ghent

• Filip Van den Bosch, Prof. dr · UZ Ghent

• Philippe Carron, Dr. · Uz Ghent

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-08-24

Primary Completion

2025-05-31

Completion

2028-12-31

FDA Drug

Yes

Countries

• Belgium

Study Locations