Clinical trial NCT05747651: 3TR (Taxonomy, Treatment, Targets and Remission) Systemic Lupus Erythematosus Study Protocol 2
Official title: 3TR (Taxonomy, Treatment, Targets and Remission) Systemic Lupus Erythematosus Study Protocol 2
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: Systemic
Lupus
Erythematosus
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
First posted: 2023-02-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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).

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

Primary outcomes:
measure: 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.
timeFrame: 52 weeks
Secondary outcomes:
measure: SLE Responder Index (SRI)-4, SRI-5 and SRI-6 response (at all time points)
timeFrame: 52 weeks
measure: Time to BICLA response.
timeFrame: 52 weeks
measure: Time to SRI response.
timeFrame: 52 weeks
measure: Failure to attain BICLA response (at all time points).
timeFrame: 52 weeks
measure: Failure to attain SRI-4, SRI-5 and SRI-6 response (at all time points).
timeFrame: 52 weeks
measure: Change in SLEDAI-2K scores (at all time points).
timeFrame: 52 weeks
measure: Change in Physician's Global Assessment (PhGA, on a scale 0-3) (at all time points).
timeFrame: 52 weeks
measure: Change in Patient's Global Assessment (PGA, on a 0-10 VAS) (at all time points).
timeFrame: 52 weeks
measure: Lupus Low Disease Activity State (LLDAS), and its individual components (at all time points).
timeFrame: 52 weeks
measure: Remission according to DORIS, and its individual components (at all time points).
timeFrame: 52 weeks
measure: Flare, based on BILAG (any new worsening in BILAG, or any new BILAG A or B) or SELENASLEDAI Flare Index (SFI) (at all time points).
timeFrame: 52 weeks
measure: Renal response/non-response, according to the 2019 EULAR/EDTA recommendations.
timeFrame: 52 weeks
measure: Organ-specific outcome measures with CLASI for mucocutaneous involvement (at all time points).
timeFrame: 52 weeks
measure: Organ-specific outcome measures with 44 joint assessment of tender and swollen joints for articular involvement (at all time points).
timeFrame: 52 weeks
measure: Worsening in SLICC/ACR Damage Index (SDI) score (at week 52).
timeFrame: 52 weeks
measure: Health-related quality of life (HRQoL) assessed with EQ-5D-5L (at week 26 and week 52).
timeFrame: 52 weeks
measure: Health-related quality of life (HRQoL) assessed with FACIT-F (at week 26 and week 52).
timeFrame: 52 weeks
measure: Health-related quality of life (HRQoL) assessed with Medical Outcomes Study 36-item Short Form health survey (SF-36) (at week 26 and week 52).
timeFrame: 52 weeks
measure: Health-related quality of life (HRQoL) assessed with Epworth Sleepiness scale (ESS) (at week 26 and week 52).
timeFrame: 52 weeks
measure: Health-related quality of life (HRQoL) assessed with Lupus-QoL (at week 26 and week 52).
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of or time to BICLA.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of or time to SLE Responder Index (SRI).
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of LLDAS.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of DORIS.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of SLEDAI-2K.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of PhGA.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of PGA.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on SDI scores.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of change in organ specific index scores.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with EQ-5D-5L.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with FACIT-F.
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with Medical Outcomes Study 36-item Short Form health survey (SF-36).
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with Epworth Sleepiness scale (ESS).
timeFrame: 52 weeks
measure: Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with Lupus-QoL.
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Brest
country: France
facility: CHU Brest
Study officials:
affiliation: CHU Brest
name: Sandrine Jousse-Joulin
role: PRINCIPAL_INVESTIGATOR
References: