3TR (Taxonomy, Treatment, Targets and Remission) Systemic Lupus Erythematosus Study Protocol 2
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •1. Serological activity only without signs of clinically active disease.
- •2. Pregnancy and/or breastfeeding.
- •3. Unable/unaware to participate in the study
研究组 & 干预措施
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).
干预措施: Blood sample (Biological)
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).
干预措施: Urine sample (Biological)
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).
干预措施: Saliva sample (Biological)
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).
干预措施: Stool sample (Biological)
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).
干预措施: Tissue sample (Biological)
结局指标
主要结局
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.
时间窗: 52 weeks
次要结局
- Failure to attain SRI-4, SRI-5 and SRI-6 response (at all time points).(52 weeks)
- Change in Patient's Global Assessment (PGA, on a 0-10 VAS) (at all time points).(52 weeks)
- Lupus Low Disease Activity State (LLDAS), and its individual components (at all time points).(52 weeks)
- SLE Responder Index (SRI)-4, SRI-5 and SRI-6 response (at all time points)(52 weeks)
- Time to BICLA response.(52 weeks)
- Change in SLEDAI-2K scores (at all time points).(52 weeks)
- Worsening in SLICC/ACR Damage Index (SDI) score (at week 52).(52 weeks)
- Time to SRI response.(52 weeks)
- Remission according to DORIS, and its individual components (at all time points).(52 weeks)
- 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).(52 weeks)
- Renal response/non-response, according to the 2019 EULAR/EDTA recommendations.(52 weeks)
- Organ-specific outcome measures with CLASI for mucocutaneous involvement (at all time points).(52 weeks)
- Organ-specific outcome measures with 44 joint assessment of tender and swollen joints for articular involvement (at all time points).(52 weeks)
- Failure to attain BICLA response (at all time points).(52 weeks)
- Change in Physician's Global Assessment (PhGA, on a scale 0-3) (at all time points).(52 weeks)
- Health-related quality of life (HRQoL) assessed with EQ-5D-5L (at week 26 and week 52).(52 weeks)
- 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).(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of DORIS.(52 weeks)
- Health-related quality of life (HRQoL) assessed with FACIT-F (at week 26 and week 52).(52 weeks)
- Health-related quality of life (HRQoL) assessed with Lupus-QoL (at week 26 and week 52).(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of or time to BICLA.(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of or time to SLE Responder Index (SRI).(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of LLDAS.(52 weeks)
- Health-related quality of life (HRQoL) assessed with Epworth Sleepiness scale (ESS) (at week 26 and week 52).(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of SLEDAI-2K.(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of PhGA.(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of PGA.(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on SDI scores.(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on attainment of change in organ specific index scores.(52 weeks)
- 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.(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with FACIT-F.(52 weeks)
- 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).(52 weeks)
- 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).(52 weeks)
- Impact of anti-SARS-CoV-2 antibodies of different isotypes (IgA, IgG, IgM) on Health-related quality of life (HRQoL) assessed with Lupus-QoL.(52 weeks)