SPondyloArthritis: inducing drug-free Remission by early TNF-Alpha bloCkade Under guidance of Single cell RNA sequencing and epigenetic profiling (SPARTACUS).

Start 21 Aug 2020 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 6 sites · Protocol SPARTACUS

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ongoing, recruitment ended

Participants planned 150

Countries 1

Sites 6

Peripheral Spondyloarthritis

Key facts

Sponsor: Universitair Ziekenhuis Gent
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
Trial duration: 21 Aug 2020 → ongoing
Decision date (initial): 2024-09-02
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: MSD Belgium · VIB

External identifiers

EU CT number: 2023-510085-27-00
EudraCT number: 2019-004961-42
ClinicalTrials.gov: NCT04435288

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Efficacy, Therapy

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).

Secondary objectives 1

To try to define the window of opportunity within which temporary treatment with bDMARDs might be more effective, by analysing patients according to symptom duration, either as continuous variable or by comparing patients with shorter symptom duration (<3 months) versus those with more longstanding disease (between 3-12 months of symptom duration).

Conditions and MedDRA coding

Peripheral Spondyloarthritis

Version	Level	Code	Term	System organ class
24.1	PT	10085753	Peripheral spondyloarthritis	100000004859

Study design 1 period

#	Title	Allocation	Blinding	Roles blinded	Arms
1	A randomized Phase III trial (SPARTACUS) Multicenter double blind randomized placebo controlled trial	Randomised Controlled	Double	[{"id":129511,"code":3,"name":"Monitor"},{"id":129514,"code":5,"name":"Carer"},{"id":129512,"code":4,"name":"Analyst"},{"id":129513,"code":2,"name":"Investigator"},{"id":129510,"code":1,"name":"Subject"}]

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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.

Exclusion criteria 17

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 sulphasalazin
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Proportion of patients achieving clinical remission.

Secondary endpoints 7

Comparison between the "TNFi induction" group and the "csDMARD Step-up" group regarding:Achievement of "sustained clinical remission" at week 24 (and week 36 for the patients remaining on blinded study medication).
Comparison between the "TNFi induction" group and the "csDMARD Step-up" group regarding: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).
Comparison between the "TNFi induction" group and the "csDMARD Step-up" group regarding: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.
Comparison between the "TNFi induction" group and the "csDMARD Step-up" group regarding:Improvement from baseline to week 12 and 24 in inflammatory parameters (ESR, CRP).
Comparison between the "TNFi induction" group and the "csDMARD Step-up" group regarding: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. Exploration of difference in percentage of patients that reach (sustained) clinical remission according to symptom duration (<3 months versus ≥3 month and <12 months).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Simponi 50 mg solution for injection in pre-filled pen.

PRD3357013 · Product

Active substance: Golimumab
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 0.02 ml millilitre(s)
Max total dose: 4.5 ml millilitre(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L04AB06 — -
Marketing authorisation: EU/1/09/546/001
MA holder: JANSSEN BIOLOGICS B.V.
MA country: Norway
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Simponi 50 mg solution for injection in pre-filled pen.

PRD3353095 · Product

Active substance: Golimumab
Pharmaceutical form: SOLUTION FOR INJECTION IN PRE-FILLED PEN
Route of administration: SUBCUTANEOUS
Max daily dose: 0.02 ml millilitre(s)
Max total dose: 4.5 ml millilitre(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L04AB06 — -
Marketing authorisation: EU/1/09/546/001
MA holder: JANSSEN BIOLOGICS B.V.
MA country: Liechtenstein
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Simponi 50 mg solution for injection in pre-filled pen.

PRD3349069 · Product

Active substance: Golimumab
Pharmaceutical form: SOLUTION FOR INJECTION IN PRE-FILLED PEN
Route of administration: SUBCUTANEOUS
Max daily dose: 0.02 ml millilitre(s)
Max total dose: 4.5 ml millilitre(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L04AB06 — -
Marketing authorisation: EU/1/09/546/001
MA holder: JANSSEN BIOLOGICS B.V.
MA country: Iceland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Simponi 50 mg solution for injection in pre-filled pen.

PRD708225 · Product

Active substance: Golimumab
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 0.02 ml millilitre(s)
Max total dose: 4.5 ml millilitre(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L04AB06 — -
Marketing authorisation: EU/1/09/546/001
MA holder: JANSSEN BIOLOGICS B.V.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Simponi 50 mg solution for injection in pre-filled syringe.

PRD3353121 · Product

Active substance: Golimumab
Pharmaceutical form: SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
Route of administration: SUBCUTANEOUS
Max daily dose: 0.02 ml millilitre(s)
Max total dose: 4.5 ml millilitre(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L04AB06 — -
Marketing authorisation: EU/1/09/546/003
MA holder: JANSSEN BIOLOGICS B.V.
MA country: Liechtenstein
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Encapsulation for blinding purposes

Simponi 50 mg solution for injection in pre-filled syringe.

PRD3357024 · Product

Active substance: Golimumab
Pharmaceutical form: SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
Route of administration: SUBCUTANEOUS
Max daily dose: 0.02 ml millilitre(s)
Max total dose: 4.5 ml millilitre(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L04AB06 — -
Marketing authorisation: EU/1/09/546/003
MA holder: JANSSEN BIOLOGICS B.V.
MA country: Norway
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Encapsulation for blinding purposes

Simponi 50 mg solution for injection in pre-filled syringe.

PRD3349081 · Product

Active substance: Golimumab
Pharmaceutical form: SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE
Route of administration: SUBCUTANEOUS
Max daily dose: 0.02 ml millilitre(s)
Max total dose: 4.5 ml millilitre(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L04AB06 — -
Marketing authorisation: EU/1/09/546/003
MA holder: JANSSEN BIOLOGICS B.V.
MA country: Iceland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Encapsulation for vlinding purposes

Simponi 50 mg solution for injection in pre-filled syringe.

PRD708234 · Product

Active substance: Golimumab
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 0.02 ml millilitre(s)
Max total dose: 4.5 ml millilitre(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L04AB06 — -
Marketing authorisation: EU/1/09/546/003
MA holder: JANSSEN BIOLOGICS B.V.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Encapsulation for blinding purposes

Comparator 3

Ledertrexate 2,5 mg Tabletten

PRD1968431 · Product

Active substance: Methotrexate Disodium
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 2.85 mg milligram(s)
Max total dose: 720 mg milligram(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L01BA01, L04AX03 — METHOTREXATE, -
Marketing authorisation: BE003446
MA holder: PFIZER S.A.
MA country: Belgium
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Encapsulation for blinding purposes

LEDERTREXATE 2,5 mg tabletten

PRD848221 · Product

Active substance: Methotrexate Disodium
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 2.85 mg milligram(s)
Max total dose: 720 mg milligram(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L01BA01, L04AX03 — METHOTREXATE, -
Marketing authorisation: BE003446
MA holder: PFIZER S.A.
MA country: Belgium
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Encapsulation for blinding purposes

LEDERTREXATE 2,5 mg comprimés

PRD411669 · Product

Active substance: Methotrexate Disodium
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 2.85 mg milligram(s)
Max total dose: 720 mg milligram(s)
Max treatment duration: 36 Week(s)
Authorisation status: Authorised
ATC code: L01BA01, L04AX03 — METHOTREXATE, -
Marketing authorisation: BE003446
MA holder: PFIZER S.A.
MA country: Belgium
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: Yes
Modification description: Encapsulation for blinding purposes

Placebo 2

The Placebo product (with the exception of the active substance), is manufactured by the same manufacturer, as the Golimumab Blinded IMP and is not sterile.

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

Placebo Ledertrexate

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Ziekenhuis Gent

Sponsor organisation: Universitair Ziekenhuis Gent
Address: Corneel Heymanslaan 10
City: Gent
Postcode: 9000
Country: Belgium

Scientific contact point

Organisation: Universitair Ziekenhuis Gent
Contact name: Prof. dr. Filip Van den Bosch

Public contact point

Organisation: Universitair Ziekenhuis Gent
Contact name: Prof. dr. Filip Van den Bosch

Locations

1 EU/EEA country · 6 investigational sites

By country

Country	MS status	Planned subjects	Sites
Belgium	Ongoing, recruitment ended	150	6
Rest of world	—	0	—

Investigational sites

Belgium

6 sites · Ongoing, recruitment ended

Het Ziekenhuisnetwerk Antwerpen

Reumatologie, Lange Bremstraat 70, 2170, Antwerp

Az St-Jan Brugge-Oostende A.V.

Reumatologie, Ruddershove 10, 8000, Brugge

Algemeen Stedelijk Ziekenhuis Campus Aalst

Reumatologie, Merestraat 80, 9300, Aalst

Az Maria Middelares Gent

Reumatology, Buitenring-Sint-Denijs 30, 9000, Gent

Universitair Ziekenhuis Gent

Reumatologie, Corneel Heymanslaan 10, 9000, Gent

UZ Leuven

Reumatologie, Herestraat 49, 3000, Leuven

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
Belgium	2020-08-21		2020-08-21	2025-02-19

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Protocol (for publication)	D1_Protocol 2023-510085-27-00_for publication	5.0
Protocol (for publication)	D2_Patient facing_Subject diary NSAIDs_Clean_for publication	2.0
Protocol (for publication)	D2_Patient facing_Subject diary_geblindeerd_Clean__for publication	2.0
Protocol (for publication)	D2_Patient facing_Subject diary_open label_Clean__for publication	2.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements	1
Subject information and informed consent form (for publication)	L1_SIS and ICF Biobank NL_Clean_for publication	2.0
Subject information and informed consent form (for publication)	L1_SIS and ICF NL_for publication	4.0
Subject information and informed consent form (for publication)	L2_Informed consent procedure_for publication	1.0
Summary of Product Characteristics (SmPC) (for publication)	E2 SmPC Golilumab	1
Summary of Product Characteristics (SmPC) (for publication)	E2 SmPC Golilumab	1
Summary of Product Characteristics (SmPC) (for publication)	E2 SmPC Methotrexate	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis English 2023-510085-27-00_for publication	4.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis_FR_Clean_for publication	2.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis_GER_Clean_for publication	2.0
Synopsis of the protocol (for publication)	D1_Protocol synopsis_NL_Clean_for publication	2.0

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-08-22	Belgium	Acceptable with conditions 2024-08-30	2024-09-02
2	SUBSTANTIAL MODIFICATION	SM-1	2025-02-19	Belgium	Acceptable 2025-04-15	2025-04-24
3	NON SUBSTANTIAL MODIFICATION	NSM-1	2025-06-10	Belgium	Acceptable 2025-04-15	2025-06-10