Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
- Conditions
- Systemic Lupus Erythematosus
- Interventions
- Registration Number
- NCT05666336
- Lead Sponsor
- Fen Li
- Brief Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal activation of B lymphocytes, which may result in many adverse consequences and even death if not treated actively. Telitacicept, approved conditionally in China in March 2021, is a biologic agent targeting B lymphocyte stimulator (BLyS）and a proliferating inducing ligand (APRIL) dually for patients with active SLE patients who have not responded to conventional treatment. The investigators hope to screen predictive biomarkers of efficacy and explore the mechanism of difference in efficacy of Telitacicept with Chinese characteristics by omics.
- Detailed Description
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal activation of B lymphocytes, which may result in many adverse consequences and even death if not treated actively. Due to the poor therapeutic efficacy and prominent adverse reactions after long-term use of glucocorticoid combined immunosuppressants, the development of targeted drug use for SLE has become a hot area of research for several years. Telitacicept, approved conditionally in China in March 2021, is a biologic agent targeting B lymphocyte stimulator (BLyS）and a proliferating inducing ligand (APRIL) dually for patients with active SLE patients who have not responded to conventional treatment. As another important part of targeted drug use, the research on biomarkers predictive of drug response is also in full swing in the treatment of SLE. The omics technology has unique advantages in screening biomarkers and exploring the mechanism of drug action. The integrated analysis of multi omics can mutually verify and supplement the screening results of a single omics, so as to more systematically and comprehensively analyze the biological molecular functions and regulatory mechanisms. Therefore, this topic selects serum proteomics combined with metabolomics to screen biomarkers for the prediction of the efficacy of Telitacicept, and to explore the mechanism of the difference in the efficacy of Telitacicept, with a view to providing meaningful reference for the exploration of SLE precise treatment.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- Patients with a clinical diagnosis of SLE according to American College of Rheumatology (ACR) classification criteria 1997 and clinically active disease.
- Patients with good compliance, will sign the informed consent before the test.
- Patients who have received conventional treatment for SLE, and the type and dose of treatment drugs have been stable for at least 30 days.
- Patients who have a positive anti-nuclear antibody test result and SELENA-SLEDAI score ≥8 at screening. If there is a low complement and/or positive anti-dsDNA antibody, the SELENA-SLEDAI score can be defined as ≥ 6 points.
- Patients with severe lupus nephritis, defined as urinary protein > 6g /24 hours or serum creatinine > 221μmol/L within the last 2 months, or who require hemodialysis.
- Patients with SLE-caused or non-SLE-caused central nervous system disease within the last 2 months.
- Patients with severe condition in blood, important organs including heart, liver, gastrointestinal tract and endocrine system which are not related with SLE.
- Patients who use prednisone ≥100mg/d over 14 days or receive plasma replacement and suffer from active infection within the last 1 month.
- Patients who received any other targeted agents over the past 12 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental Group Telitacicept The treatment regimen consists of four drugs, a glucocorticoid plus Telitacicept plus hydroxychloroquine plus an immunosuppressor. Prednisone(30mg, Qd) or Methylprednisolone(24mg, Qd) plus Telitacicept(160mg, Qw) plus Hydroxychloroquine (0.2g, Qd) plus cyclophosphamide(0.8g, Qm) or Mycophenolate Mofetil (0.5g, Bid) or Tacrolimus (1mg, Bid) The above treatment will continue for 24 weeks. Experimental Group Hydroxychloroquine The treatment regimen consists of four drugs, a glucocorticoid plus Telitacicept plus hydroxychloroquine plus an immunosuppressor. Prednisone(30mg, Qd) or Methylprednisolone(24mg, Qd) plus Telitacicept(160mg, Qw) plus Hydroxychloroquine (0.2g, Qd) plus cyclophosphamide(0.8g, Qm) or Mycophenolate Mofetil (0.5g, Bid) or Tacrolimus (1mg, Bid) The above treatment will continue for 24 weeks. Experimental Group Prednisone The treatment regimen consists of four drugs, a glucocorticoid plus Telitacicept plus hydroxychloroquine plus an immunosuppressor. Prednisone(30mg, Qd) or Methylprednisolone(24mg, Qd) plus Telitacicept(160mg, Qw) plus Hydroxychloroquine (0.2g, Qd) plus cyclophosphamide(0.8g, Qm) or Mycophenolate Mofetil (0.5g, Bid) or Tacrolimus (1mg, Bid) The above treatment will continue for 24 weeks. Experimental Group Cyclophosphamide The treatment regimen consists of four drugs, a glucocorticoid plus Telitacicept plus hydroxychloroquine plus an immunosuppressor. Prednisone(30mg, Qd) or Methylprednisolone(24mg, Qd) plus Telitacicept(160mg, Qw) plus Hydroxychloroquine (0.2g, Qd) plus cyclophosphamide(0.8g, Qm) or Mycophenolate Mofetil (0.5g, Bid) or Tacrolimus (1mg, Bid) The above treatment will continue for 24 weeks. Experimental Group Mycophenolate Mofetil The treatment regimen consists of four drugs, a glucocorticoid plus Telitacicept plus hydroxychloroquine plus an immunosuppressor. Prednisone(30mg, Qd) or Methylprednisolone(24mg, Qd) plus Telitacicept(160mg, Qw) plus Hydroxychloroquine (0.2g, Qd) plus cyclophosphamide(0.8g, Qm) or Mycophenolate Mofetil (0.5g, Bid) or Tacrolimus (1mg, Bid) The above treatment will continue for 24 weeks. Experimental Group Tacrolimus The treatment regimen consists of four drugs, a glucocorticoid plus Telitacicept plus hydroxychloroquine plus an immunosuppressor. Prednisone(30mg, Qd) or Methylprednisolone(24mg, Qd) plus Telitacicept(160mg, Qw) plus Hydroxychloroquine (0.2g, Qd) plus cyclophosphamide(0.8g, Qm) or Mycophenolate Mofetil (0.5g, Bid) or Tacrolimus (1mg, Bid) The above treatment will continue for 24 weeks. Experimental Group Methylprednisolone The treatment regimen consists of four drugs, a glucocorticoid plus Telitacicept plus hydroxychloroquine plus an immunosuppressor. Prednisone(30mg, Qd) or Methylprednisolone(24mg, Qd) plus Telitacicept(160mg, Qw) plus Hydroxychloroquine (0.2g, Qd) plus cyclophosphamide(0.8g, Qm) or Mycophenolate Mofetil (0.5g, Bid) or Tacrolimus (1mg, Bid) The above treatment will continue for 24 weeks.
- Primary Outcome Measures
Name Time Method SLE Responder Index (SRI) 4 response rate week 24 (1) Definition of SRI4: ≥4 point reduction from baseline in SELENA-SLEDAI score, no worsening (\<0.3 point increase from baseline) in Physician's Global Assessment (PGA) and no new British Isles Lupus Assessment Group (BILAG) A organ domain score or two new BILAG B organ domain scores vs baseline. (2) The patients acquired SRI4 were classified as Good Responders (GR), The patients not acquired SRI4 were classified as Non-Responders (NR).
- Secondary Outcome Measures
Name Time Method The changes of glucocorticoids dose week 24 The percentage of patients whose average prednisone dose was ≤7.5 mg/day or reduced by ≥25% from baseline.
Metabonomics week 24 Screening and comparison of different metabolites
The variation of serum markers week 24 The variation of serum markers including BLyS,APRIL,CD19+B lymphocytes count, anti-dsDNA antibodies, IgG, IgA, IgM, complement3(C3), and complement4(C4) at baseline and after 24 weeks' treatment.
Proteomics week 24 Screening and comparison of different proteins
Trial Locations
- Locations (1)
Department of Rheumatology and Immunology, Xiangya Second Hospital, Central South University
🇨🇳Changsha, Hunan, China