3TR (Taxonomy, Treatment, Targets and Remission) Systemic Lupus Erithematosus Study Protocol (3TR-SLE1)

Regional University Hospital Center (CHRU)

Status and phase: Active, not recruiting; Phase 3

Conditions: Systemic Lupus Erythematosus (SLE)

Treatments: Biological: Saliva sample; Biological: Urine sample; Biological: Stood sample; Procedure: Tissue sample; Biological: Blood sample

Study type: Interventional

Funder types: Other

Identifiers

NCT05458622

29BRC21.0367 (3TR-SLE1)

Details and patient eligibility

About

The natural history of Systemic lupus erythematosus (SLE) is characterized by relapses or flares alternated with periods of remission. Flares are associated with accrual of organ damage independently of other risk factors, both contributing to a considerable morbidity. No useful biomarker is currently available to predict which patients with a quiescent disease are at risk of flare.

The 3TR project (funded by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 831434, and supported by European Union's Horizon 2020 research and innovation programme and EFPIA) is a transdisciplinary consortium that primary aims at identifying biosignatures as predictors of response and non-response to therapy in seven different autoimmune, allergic and inflammatory diseases, including SLE. 3TR will perform a longitudinal multi-dimensional molecular analysis in patients with these diseases. A molecular profiling approach is a modern and innovative way to investigate and stratify heterogeneous diseases on the basis of their common biomolecular pathways. The main hypothesis of the 3TR project is that data obtained from multiomic analysis across the seven different diseases will identify shared biological pathways that better predict the response or non-response to therapy despite their differences in terms of clinical phenotypes and pathogenetic mechanisms. Therefore patients from multiple European centers participating in 3TR will be recruited for a longitudinal clinical follow-up and collections of several samples that will be used to perform multi-omic analysis.

Full description

The study will be carried out in the framework of the IMI2 (innovative medicine initiative) and EFPIA (European Federation of Pharmaceutical Industries and Associations)-funded 3TR (Taxonomy, Treatment, Targets and Remission) project. The programme is supported by the European Union's Horizon 2020 research and innovation programme. 3TR is funded under the grant agreement No 831434 and it runs from 2019 to 2026.

3TR is a transdisciplinary consortium that aims to perform a longitudinal multi-dimensional molecular analysis in patients with autoimmune, allergic and inflammatory diseases. A molecular profiling approach is a modern and innovative way to investigate and stratify heterogeneous diseases on the basis of their common biomolecular pathways. The main hypothesis of the 3TR project is that data obtained from multiomic analysis across seven different diseases, including SLE, will identify shared biological pathways that better predict the response or non-response to therapy despite their differences in terms of clinical phenotypes and pathogenetic mechanisms. Patients from multiple European centers participating in 3TR will be recruited for a longitudinal clinical follow-up and collections of several samples that will be used to perform multi-omic analysis.

Several innovations are expected within the 3TR project to increase the knowledge of pathogenetic mechanisms underlying the clinical phenotypes in SLE, and to unravel, in the complexity of SLE biomolecular heterogeneity, the pathways of response or non-response to treatment, as well as, at an earlier stage, the processes that may lead to disease flare. These insights could ultimately allow the possibility to effectively practice prevention and counselling, to adopt measures of personalized treatment or to perform drug repurposing using the knowledge gained from the SLE studies and the studies on other diseases within the 3TR project.

Moreover, the impact of the COVID-19 viral pandemic will be implemented in our research. More specifically, we will investigate the impact of the presence of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on the development of flare, as well as on the response or non-response to immunomodulatory therapy.

To implement the strategy, a two-step research has been designed, and comprises:

1. The flare biomarker study (3TR SLE 1) is considered a "feeding" phase before the main part. Patients who meet the inclusion criteria for 3TR SLE 2 will be proposed to participate in the second study.
2. The response biomarker study (3TR SLE 2), which is a prospective study (main part).

The present protocol relates to the flare biomarker study (3TR SLE 1).

Enrollment: 25 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Age at the time of inclusion ≥ 18 years;
2. Able to consent and agree to participate to the study.
3. Diagnosis of SLE according to the EULAR/ACR criteria; BILAG C, D or E only;
4. No restriction regarding current or previous therapies, except for hydroxychloroquine (HCQ) or chloroquine treatment which should be administered unless contraindicated or documented intolerance in the past.

Exclusion criteria

1. Pregnancy and/or breastfeeding;
2. Initiation or intensification of immunosuppressive therapy or a prednisone equivalent dose of > 10 mg/day within 30 days prior to baseline;
3. Unable or unaware to participate to the study.

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 1 patient group

Stable or quiescent SLE

Other group

Description:

Patients included in this study will undergo one assessment at the time of recruitment and at the time of the end of study (time of a flare or at least 24 months after inclusion) The following information will be collected : * General data: date of flare. * Disease activity: BILAG; SLEDAI-2K; PhGA (0-3); PGA (0-10); LLDAS; DORIS ; CLASI for mucocutaneous involvement; 44 joint assessment; proteinuria (UPCR); serum creatinine and eGFR for lupus nephritis. * Organ damage: SLICC/ACR Damage Index. * Kidney histopathology * HRQoL: EQ-5D-5L; FACIT-F; Medical Outcomes Study 36-item Short Form health survey (SF-36); Epworth Sleepiness scale (ESS); Lupus-QoL. * Start day and current dose for current treatments Biological samples which will be obtained twice, at baseline and at the time of the first flare documented over 24 months, or at month 24 if no flare has been documented: * Blood * Urine * Stool * Saliva * Tissue samples for organ-specific manifestations

Treatment:

Biological: Blood sample

Procedure: Tissue sample

Biological: Stood sample

Biological: Urine sample

Biological: Saliva sample