Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients

Sponsor

Fen Li (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05666336

Collaborator

(none)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Biological: Telitacicept Drug: Hydroxychloroquine Drug: Prednisone Drug: Methylprednisolone Drug: Cyclophosphamide Drug: Mycophenolate Mofetil Drug: Tacrolimus	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Proteomics Combined With Metabolomics Studies on the Efficacy of Telitacicept in Chinese Patients of Systemic Lupus Erythematosus

Anticipated Study Start Date :

Dec 31, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental Group 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.	Biological: Telitacicept It is necessary and will be given by subcutaneous injection of 160mg/week for 24 weeks. Other Names: RC18 Drug: Hydroxychloroquine It is necessary and will be given by oral administration of 0.2g/day for 24 weeks. Other Names: HCQ Drug: Prednisone It is permitted which can be interchangeable with methylprednisolone. It will be given by oral administration of 30mg/day from beginning and be lowed dosage during the treatment of 24 weeks. Other Names: PRED Drug: Methylprednisolone It is permitted which can be interchangeable with prednisone. It will be given by oral administration of 24mg/day from beginning and be lowed dosage during the treatment of 24 weeks. Other Names: MP Drug: Cyclophosphamide It is permitted which can be interchangeable with mycophenolate mofetil or tacrolimus. It will be given by oral administration of 0.8g/month for 24 weeks. Other Names: CTX Drug: Mycophenolate Mofetil It is permitted which can be interchangeable with cyclophosphamide or tacrolimus. It will be given by oral administration of 0.5g twice a day for 24 weeks. Other Names: MMF Drug: Tacrolimus It is permitted which can be interchangeable with cyclophosphamide or mycophenolate mofetil. It will be given by oral administration of 1mg twice a day for 24 weeks. Other Names: TAC

Arm

Intervention/Treatment

Experimental: Experimental Group

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.

Biological: Telitacicept

It is necessary and will be given by subcutaneous injection of 160mg/week for 24 weeks.

Other Names:

RC18

Drug: Hydroxychloroquine

It is necessary and will be given by oral administration of 0.2g/day for 24 weeks.

Other Names:

HCQ

Drug: Prednisone

It is permitted which can be interchangeable with methylprednisolone. It will be given by oral administration of 30mg/day from beginning and be lowed dosage during the treatment of 24 weeks.

Other Names:

PRED

Drug: Methylprednisolone

It is permitted which can be interchangeable with prednisone. It will be given by oral administration of 24mg/day from beginning and be lowed dosage during the treatment of 24 weeks.

Other Names:

Drug: Cyclophosphamide

It is permitted which can be interchangeable with mycophenolate mofetil or tacrolimus. It will be given by oral administration of 0.8g/month for 24 weeks.

Other Names:

CTX

Drug: Mycophenolate Mofetil

It is permitted which can be interchangeable with cyclophosphamide or tacrolimus. It will be given by oral administration of 0.5g twice a day for 24 weeks.

Other Names:

MMF

Drug: Tacrolimus

It is permitted which can be interchangeable with cyclophosphamide or mycophenolate mofetil. It will be given by oral administration of 1mg twice a day for 24 weeks.

Other Names:

TAC

Outcome Measures

Primary Outcome Measures

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

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.
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
Metabonomics [week 24]
Screening and comparison of different metabolites

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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.

Exclusion Criteria:

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.