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

Systemic Lupus Erythematosus (SLE) Clinical Trial

— 3TR-SLE2  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05747651
• Other study ID #: 29BRC22.1068 (3TR-SLE2)
• Status: Recruiting
• Start date: March 27, 2023
• Est. completion date: March 27, 2027

Study information

• Verified date: April 2023
• Source: University Hospital, Brest
• Contact: Sandrine Jousse-Joulin
• Phone: +332 98 34 72 68
• Email: sandrine.jousse-joulin[@]chu-brest.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 5
• Est. completion date: March 27, 2027
• Est. primary completion date: March 27, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus (SLE)

Intervention

Biological:
• Blood sample
Total volume of blood (on each sampling occasion): 54,5mL.
• Urine sample
Urine: 100 mL which will be centrifuged. The pellet will be frozen, and the urine supernatant will be aliquoted.
• Saliva sample
Saliva: will be collected in special container for saliva microbiome and methylation.
• Stool sample
Stool: One sample for microbiome to be sent to the biobank, frozen at -80 °C.
• 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.

Locations

Country	Name	City	State
France	CHU Brest	Brest

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Brest

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	SLE Responder Index (SRI)-4, SRI-5 and SRI-6 response (at all time points)	The outcome measure correponds to an improve of at least 4, 5 or 6 of SLEDAI-2K score, no aggravation of BILAG A or B score and no aggravation of the PhGA.	52 weeks
Secondary	Time to BICLA response.		52 weeks
Secondary	Time to SRI response.		52 weeks
Secondary	Failure to attain BICLA response (at all time points).	The BICLA measurement has no unit.	52 weeks
Secondary	Failure to attain SRI-4, SRI-5 and SRI-6 response (at all time points).	The outcome measure correponds to a failure to attain at least 4, 5 or 6 of SLEDAI-2K score, no aggravation of BILAG A or B score and no aggravation of the PhGA.	52 weeks
Secondary	Change in SLEDAI-2K scores (at all time points).	The change in the SLEDAI-2K is a number without unit to see change in the SLEDAI score. The SLEDAI score is obtained on a scale 0-115.	52 weeks
Secondary	Change in Physician's Global Assessment (PhGA, on a scale 0-3) (at all time points).	The Physician's Global Assessment (PhGA) is a number without unit on a scale 0-3.	52 weeks
Secondary	Change in Patient's Global Assessment (PGA, on a 0-10 VAS) (at all time points).	The Patient's Global Assessment (PGA) is a patient assessment without unit on a scale 0-10.	52 weeks
Secondary	Lupus Low Disease Activity State (LLDAS), and its individual components (at all time points).	The Lupus Low Disease Activity State (LLDAS) is assessed as "present" or "absent".	52 weeks
Secondary	Remission according to DORIS, and its individual components (at all time points).	The Remission according to DORIS is assessed as "present" or "absent". DORIS is a score obtained when patient has 0mg of corticoisteroids and a stable treatment with no activity of the disease.	52 weeks
Secondary	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).	The flare based on BILAG is assessed as "yes" or "no".	52 weeks
Secondary	Renal response/non-response, according to the 2019 EULAR/EDTA recommendations.		52 weeks
Secondary	Organ-specific outcome measures with CLASI for mucocutaneous involvement (at all time points).	The CLASI activity is ranged from 0-70, with higher scores indicating more severe skin disease. It evaluates through 13 anatomical regions erythema and scale hypertrophy (from 0 to 3 and 0 to 2 respectively). The activity scores of 0-9 indicating mild disease, 10-20 indicating moderate disease, and 21-70 indicating severe disease. It is also a useful tool in determining whether or not patients responded to treatment, as patients who improved clinically had a mean a 4-point or 20% decrease in the CLASI activity score to identify improvement.	52 weeks
Secondary	Organ-specific outcome measures with 44 joint assessment of tender and swollen joints for articular involvement (at all time points).		52 weeks
Secondary	Worsening in SLICC/ACR Damage Index (SDI) score (at week 52).	The Worsening in SLICC/ACR Damage Index (SDI) score is assessed by a binary response as "present" or "absent". The SLICC/ACR Damage Index (SDI) is the score of the damage of the disease and is a number out of 46 without unit.	52 weeks
Secondary	Health-related quality of life (HRQoL) assessed with EQ-5D-5L (at week 26 and week 52).	EQ-5D-5L evaluates health-related quality of life via a descriptive system and a visual analogue scale. The descriptive system comprises a list of quotes divided in five dimensions: mobility, self-care, usual activities, pain and discomfort and anxiety and depression. For each dimension, the patient choses a level of severity of his/her condition by selecting one quote among five propositions. The visual analogue scale is used for the patient to rate his/her general health condition on a scale of 1 to 100.	52 weeks
Secondary	Health-related quality of life (HRQoL) assessed with FACIT-F (at week 26 and week 52).	FACIT-F is a tool to assess tiredness where the patient tiredness is rated by replying to 13 quotes on a 5-point scale going from "not at all" to "very much".	52 weeks
Secondary	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).	SF-36 is a patient-reported short form health survey composed of 36 items.	52 weeks
Secondary	Health-related quality of life (HRQoL) assessed with Epworth Sleepiness scale (ESS) (at week 26 and week 52).	The ESS is a self-administered questionnaire with 8 questions where patients are asked to rate on a 4-point scale (0-3) their usual chances of dozing off or falling asleep while engaged in eight different activities.	52 weeks
Secondary	Health-related quality of life (HRQoL) assessed with Lupus-QoL (at week 26 and week 52).	The LupusQoL is a lupus-specific HRQOL questionnaire consisting of 34 items grouped in eight domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image and fatigue. A score from 0 to 100 (best HRQOL) is calculated for each domain.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of or time to BICLA.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of or time to the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA). BICLA is a validated composite global measure of SLE disease activity including SLEDAI-2K, CLASI-A, OCS dosage reduction, and patient-reported outcomes.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of or time to SLE Responder Index (SRI).	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of or time to SRI. SRI is an index to evaluate the activity of the disease.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of LLDAS.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of Lupus Low Disease Activity State (LLDAS). Low disease activity is obtained when patient has 7.5 mg of corticosteroids and stable immunosuppressive treatement ans stability of the disease.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of DORIS.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of DORIS. DORIS is a score obtained when patient has 0 mg of corticoisteroids and a stable treatment with no activity of the disease. DORIS is assessed as "present" or "absent".	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of SLEDAI-2K.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of SLEDAI-2K. SLEDAI-2K is a number without unit on a 0 to 105-scale.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of PhGA.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment PhGA. The Physician's Global Assessment (PhGA) is a number without unit.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of PGA.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of PGA. The Patient's Global Assessment (PGA) is a number without unit.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on SDI scores.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on SDI score. SDI score is the score of the damage of the disease and is a number out of 46 without unit.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of change in organ specific index scores.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on organ specific index scores. The organ specific index scores are scores without unit.	52 weeks
Secondary	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.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on HRQoL assessed with EQ-5D-5L. EQ-5D-5L evaluates health-related quality of life via a descriptive system and a visual analogue scale. The descriptive system comprises a list of quotes divided in five dimensions: mobility, self-care, usual activities, pain and discomfort and anxiety and depression. For each dimension, the patient choses a level of severity of his/her condition by selecting one quote among five propositions. The visual analogue scale is used for the patient to rate his/her general health condition on a scale of 1 to 100.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with FACIT-F.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on HRQoL assessed with FACIT-F. FACIT-F is a tool to assess tiredness where the patient tiredness is rated by replying to 13 quotes on a 5-point scale going from "not at all" to "very much".	52 weeks
Secondary	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).	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on HRQoL assessed with Medical Outcomes Study 36-item Short Form health survey (SF-36). SF-36 is a patient-reported short form health survey composed of 36 items.	52 weeks
Secondary	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).	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on HRQoL with Epworth Sleepiness scale (ESS). The ESS is a self-administered questionnaire with 8 questions where patients are asked to rate on a 4-point scale (0-3) their usual chances of dozing off or falling asleep while engaged in eight different activities.	52 weeks
Secondary	Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with Lupus-QoL.	This exploratory study will observe the impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on HRQoL assessed with Lupus-QoL. The LupusQoL is a lupus-specific HRQOL questionnaire consisting of 34 items grouped in eight domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image and fatigue. A score from 0 to 100 (best HRQOL) is calculated for each domain.	52 weeks