Clinical trial
3TR (Taxonomy, Treatment, Targets and Remission) Systemic Lupus Erithematosus Study Protocol
Name
29BRC21.0367 (3TR-SLE1)
Description
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.
Trial arms
Trial start
2022-11-29
Estimated PCD
2026-11-01
Trial end
2026-11-01
Status
Recruiting
Phase
Early phase I
Treatment
Blood sample
- 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.
Arms:
Stable or quiescent SLE
Urine sample
- Urine: 100 mL which will be centrifuged. The pellet will be frozen, and the urine supernatant will be aliquoted;
Arms:
Stable or quiescent SLE
Saliva sample
- Saliva: will be collect in special container for saliva microbiome and methylation;
Arms:
Stable or quiescent SLE
Stood sample
- Stool: One sample for microbiome to be sent to the biobank, frozen at -80 °C
Arms:
Stable or quiescent SLE
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.
Arms:
Stable or quiescent SLE
Size
25
Primary endpoint
Flare patient proportion according to the BILAG index at 24 months
24 months
Eligibility criteria
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.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': '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.', 'primaryPurpose': 'SUPPORTIVE_CARE', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 25, 'type': 'ESTIMATED'}}
Updated at
2023-03-17
1 organization
4 products
1 indication
Organization
University Hospital BrestProduct
Blood sampleIndication
Systemic Lupus Erythematosus (SLE)Product
Urine sampleProduct
Saliva sampleProduct
Stood sample