3TR (Taxonomy, Treatment, Targets and Remission) Systemic Lupus Erythematosus Study Protocol 2

NCT05747651 | Active Not Recruiting

• 1 other identifier: 29BRC22.1068 (3TR-SLE2)
• Study Type: observational
• Target: 10
• 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)

• The British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 52 from baseline, including SLEDAI-2K, CLASI-A, OCS dosage reduction, and patient-reported outcomes.

  52 weeks

Secondary Outcomes (34)

• SLE Responder Index (SRI)-4, SRI-5 and SRI-6 response (at all time points)

  52 weeks

• Time to BICLA response.

  52 weeks

• Time to SRI response.

  52 weeks

• Failure to attain BICLA response (at all time points).

  52 weeks

• Failure to attain SRI-4, SRI-5 and SRI-6 response (at all time points).

  52 weeks

Study Arms (1)

Active SLE

Patients will undergo regular follow-up where routine clinical examination and laboratory assessments will be conducted, and biological samples will be obtained. The patients will be instructed to contact their center whenever they develop a symptom suspicious of flare. In such cases, an unscheduled visit will be conducted for clinical examination, assessment and sampling similar to the last visit. If a patient needs a major change in therapy at one of the scheduled visits or at an unscheduled visit, an early termination (ET) visit will be planned. Patients requiring a major change in therapy due to active disease (defined as BILAG A or B) from week 12 through week 52 will undergo two additional evaluations at week +26 and at week +52 from the time of early termination/new therapy initiation in order to determine biomarkers of secondary response after the change in therapy (herein termed secondary response) and persistent non- response (herein termed refractory disease).

Biological: Blood sample; Biological: Urine sample; Biological: Saliva sample; Biological: Stool sample; Biological: Tissue sample

Interventions

Blood sample BIOLOGICAL

Total volume of blood (on each sampling occasion): 54,5mL.

Active SLE

Urine sample BIOLOGICAL

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

Active SLE

Saliva sample BIOLOGICAL

Saliva: will be collected in special container for saliva microbiome and methylation.

Active SLE

Stool sample BIOLOGICAL

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

Active SLE

Tissue sample BIOLOGICAL

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.

Active SLE

Eligibility Criteria

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

Study Population

SLE patients with active disease, defined as a BILAG A or B within certain domains (see inclusion criteria) will be included in this study. These patients will either be directly recruited to this study or originate from the "feeding" phase (3TR-SLE, flare biomarker study, NCT05458622) when a flare is detected. There will be no restriction regarding current or previous therapies.

You may qualify if:

• \. Able to consent and agree to participate in the study.
• \. Diagnosis of SLE according to the EULAR/ACR criteria.
• \. Patients should have at least one of the following: i. active arthritis, attributed to SLE (BILAG A or B in the musculoskeletal domain).
• ii. active skin disease, attributed to SLE (BILAG A or B in the mucocutaneous domain).
• iii. active biopsy-proven lupus nephritis (LN; ISN/RPS class III, IV or V), with or without extrarenal organ involvement.
• iv. active CNS involvement as a main manifestation (with or without other organ involvement) along with initiation of new treatment for CNS involvement (BILAG A or B in the neuropsychiatric domain).
• \. Stable standard therapy for at least 30 days, including hydroxychloroquine (HCQ) or chloroquine treatment, unless contraindicated or documented intolerance.

You may not qualify if:

• \. Serological activity only without signs of clinically active disease.
• \. Pregnancy and/or breastfeeding.
• \. Unable/unaware to participate in the study

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (1)

CHU Brest

Brest, France, 29200, 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 Officials

• Sandrine Jousse-Joulin

  CHU Brest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 28, 2023
• Study Start: March 27, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 23, 2025

Record last verified: 2025-01

Locations

FR (1)