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

NCT ID: NCT05747651

Last Updated: 2025-01-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 10 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-03-27
• Study Completion Date: 2026-12-31

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.

Detailed 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 the research. More specifically, the investigators will study 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 response biomarker study (3TR SLE 2).

Conditions

Systemic Lupus Erythematosus (SLE)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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).

Blood sample

Intervention Type: BIOLOGICAL

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

Urine sample

Intervention Type: BIOLOGICAL

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

Saliva sample

Intervention Type: BIOLOGICAL

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

Stool sample

Intervention Type: BIOLOGICAL

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

Tissue sample

Intervention Type: 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.

Interventions

Blood sample

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

Intervention Type: BIOLOGICAL

Urine sample

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

Intervention Type: BIOLOGICAL

Saliva sample

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

Intervention Type: BIOLOGICAL

Stool sample

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

Intervention Type: BIOLOGICAL

Tissue sample

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 1. Age at the time of inclusion ≥ 18 years.
• 2. Able to consent and agree to participate in the study.
• 3. Diagnosis of SLE according to the EULAR/ACR criteria.
• 4. 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).

• 5. Stable standard therapy for at least 30 days, including hydroxychloroquine (HCQ) or chloroquine treatment, unless contraindicated or documented intolerance.

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Brest

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandrine Jousse-Joulin

Role: PRINCIPAL_INVESTIGATOR

CHU Brest

Locations

CHU Brest

Brest, France, France

Countries

France

Other Identifiers

29BRC22.1068 (3TR-SLE2)

Identifier Type: -

Identifier Source: org_study_id