| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| peripheral spondyloarthritis |
| Perifere spondyloartritis |
|
| E.1.1.1 | Medical condition in easily understood language |
| rheumatic inflammatory disease against the joints and tendons outside the vertebral column |
| reumatische ontstekingsziekte tegenover de gewrichten en pezen buiten de wervelzuil |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10051265 |
| E.1.2 | Term | Spondyloarthropathy |
| E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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). |
|
| E.2.2 | Secondary objectives of the trial |
| 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). |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
- 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 SpA features
- 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.
|
|
| E.4 | Principal 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.
• 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.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| proportion of patients achieving clinical remission |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Comparison between the “TNFi induction” group and the “csDMARD Step-up” group regarding:
o Achievement of “sustained clinical remission” at week 24 (and week 36 for the patients remaining on blinded study medication).
o Improvement from baseline to week 12 and 24 in individual clinical assessments (78-Tender Joint Count, 76-Swollen Joint Count, Dactylitis Count, SPARCC Enthesitis Score) and composite scores (ASDAS: Axial Spondyloarthritis Disease Activity Score).
o Improvement from baseline to week 12 and 24 in patient-reported outcomes (Patient global assessment of disease activity and pain, BASDAI, BASFI, ASAS Health Index.
o Improvement from baseline to week 12 and 24 in inflammatory parameters (ESR, CRP).
o Changes in concomitant NSAID intake (NSAID-index) and “escape” intra-articular glucocorticoid injections between baseline and week 24
- Difference in occurrence of (serious) adverse events (AEs) and AEs of specific interest between the 2 treatment strategies from baseline to week 24 (and week 36 for patients remaining on blinded study medication). Descriptive analysis of the number and type of adverse events between both strategies
- Percentage of patients achieving (sustained) clinical remission with open-label golimumab treatment after failure of the initial randomized, blinded treatment strategy.
o Exploration of difference in percentage of patients that reach (sustained) clinical remission according to symptom duration (<3 months versus ≥3 month and <12 months).
- For patients in SPARTACUS Phase B (drug-free remission period):
o Exploration of the duration of drug-free remission.
o Time to (documented) pSpA disease flare.
o Time to restart of “standard-of-care” pSpA treatment.
o Exploration of clinical parameters that could be predictive for reaching (sustained) clinical remission and/or flare.
- Correlation between the “Patient Acceptable Signs & Symptoms Improvement” (“PASSI”) and different clinical assessments, laboratory values and patient-reported outcomes (or combinations thereof).
- Predictive value of single cell RNA sequencing on baseline synovial biopsy samples with regard to the different treatment outcomes.
- Predictive value of epigenetic profiling on baseline blood samples with regard to the different treatment outcomes
- Health economic evaluation comparing for both treatment arms incremental Cost-Utility (iCUR) of initial treatment with a biological compared to usual care at (two) different time points of the window of opportunities (start treatment within 3 months or 12 months). A trial-based and lifetime modeled iCUR will be calculated.
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
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