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

NCT05458622 | Active Not Recruiting Phase 3

• 1 other identifier: 29BRC21.0367 (3TR-SLE1)
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Lupus Erythematosus (SLE)

Keywords

Systemic; Lupus; Erythematosus

Outcome Measures

Primary Outcomes (1)

• Flare patient proportion according to the BILAG index at 24 months

  Number of patients developing a flare within 24 months of follow-up, defined as a new BILAG A or B in any clinical domain.

  24 months

Secondary Outcomes (2)

• Proportion of flare according to the SELENA-SLEDAI Flare Index

  Flare or 24 months

• Anti-SARS-CoV-2 antibodies impact on risk of flare

  Flare or 24 months

Study Arms (1)

Stable or quiescent SLE

OTHER

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

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

Interventions

Blood sample BIOLOGICAL

\- Total volume of blood (on each sampling occasion): 54,5mL. * Whole blood will be collected in EDTA, 1 tube of 10 mL for DNA (genotyping, methylation arrays; at baseline for genotyping and at EOS visit for methylation arrays). From this, an aliquot of 0.5 mL for baseline cell numbers (cell proportions, CyTOF/flow cytometry) at all time points; capture of leukocytes for blood single cell RNA seq. at all time points and 5 mL for cell stimulations for cell metabolome (C13 to be added), and 1 tube of 10 mL for cell stimulations (CyTOF) at baseline.Tempus tube: 1 tube of 3 mL for RNA, 1 tube of 3mL for whole blood RNA seq.; to be taken at all time points. Plasma will be obtained and aliquoted from these tubes; to be obtained at all time points. * Serum: 2 tubes of 10 mL without anticoagulant for measurements of anti-drug antibodies, hydroxychloroquine levels, cytokines and analytes, proteome, and autoantibodies; to be taken at all time points.

Stable or quiescent SLE

Urine sample BIOLOGICAL

\- Urine: 100 mL which will be centrifuged. The pellet will be frozen, and the urine supernatant will be aliquoted;

Stable or quiescent SLE

Saliva sample BIOLOGICAL

\- Saliva: will be collect in special container for saliva microbiome and methylation;

Stable or quiescent SLE

Stood sample BIOLOGICAL

\- Stool: One sample for microbiome to be sent to the biobank, frozen at -80 °C

Stable or quiescent SLE

Tissue sample PROCEDURE

\- Tissue samples for organ-specific manifestations: * Kidney tissue in lupus nephritis: one small fragment of the fresh kidney biopsy will be stored in a 10% dimethyl sulfoxide (DMSO) solution (slow freezing to -80 °C) until shipment. * Skin tissue (at selected centers) from inflamed lesion and non-inflamed skin from the gluteal region will be obtained through punch biopsy and stored in a 10% dimethyl sulfoxide (DMSO) solution (slow freezing to -80 °C) until shipment. * Synovial tissue (at selected centers) will be obtained through ultrasound-directed arthroscopy and stored in a 10% dimethyl sulfoxide (DMSO) solution (slow freezing to -80 °C) until shipment. * Aspirate from swollen lymph nodes (at selected centers) will be obtained and stored in a 10% dimethyl sulfoxide (DMSO) solution (slow freezing to -80 °C) until shipment.

Stable or quiescent SLE

Eligibility Criteria

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

You may qualify if:

• Able to consent and agree to participate to the study.
• Diagnosis of SLE according to the EULAR/ACR criteria; BILAG C, D or E only;
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (1)

01- CHU Brest

Brest, 29609, France

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Blood Specimen Collection; Histocompatibility Testing

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Immunologic Tests; Immunologic Techniques

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients with stable or quiescent SLE will be included and followed-up in routine clinical care until a flare or until the 2 years end-of-study (EOS) visit.

Study Record Dates

• First Submitted: June 13, 2022
• First Posted: July 14, 2022
• Study Start: November 29, 2022
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: January 23, 2025

Record last verified: 2025-01

Locations

FR (1)