Telitacicept Followed With Rituximab Therapy on APS Secondary to SLE

The Clinical Efficacy and Safety of Telitacicept Followed With Rituximab Therapy on APS Secondary to SLE ，a Multicentre Observational Study

The aim of this study was to observe the clinical efficacy and safety of rituximab (RTX) combination with telitacicept (TA) in patients of systemic lupus erythematosus secondary antiphospholipid syndrome (APS).

Study Overview

• Status: Recruiting
• Conditions: Antiphospholipid Syndrome
• Intervention / Treatment: Drug: Telitacicept; Drug: Rituximab; Drug: Aspirin; Drug: Warfarin; Drug: Hydroxychloroquine; Drug: Prednisone

Detailed Description

In this multicenter, prospective, observational study, 80 patients with SLE Secondary APS patients were enrolled. RTX alone or its continuation with TA was observed for 24weeks，and extended for another 24 weeks. At week 12, the RTX group could be converted to the combination group. The primary end point was the response rate of total antiphospholipid antibody (aPL) at week 12. The secondary end points included the decline rate and value of aPL antibody, aGAPSS score, remission degree of specific clinical indicators, changes in SLE disease activity in SAPS group, and drug safety at week 12 and week 24.

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Shu Qiang, Dr.; Phone Number: 0086-0531-82169654; Email: shuqiang@sdu.edu.cn
• Study Contact Backup: Name: Zhang Xiaoyu; Phone Number: 0086-0531-82169654; Email: 1146978430@qq.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, Shandong
      • Recruiting
      • Qilu hospital
      • Contact: Xiaoyun Yang; Phone Number: 0086-0531-82169166; Email: qlyykyc@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

1. Meet the diagnostic criteria of SLE and related symptoms of secondary APS;

2. Positive LA /ACL/ aβ2GPI ,on two or more occasions, at least 12 weeks apart;

3. One or more of the following related clinical symptoms:

1. Refractory/recurrent thrombocytopenia;
2. Autoimmune hemolytic anemia;
3. Heart valve disease;
4. Renal involvement;
5. Skin ulcer;
6. arterial or deep vein thrombosis;

Description

Inclusion Criteria:

• 1.Patients who meet 2006 Sapporo classification criteria of APS or 2020 nonstandard APS performance；

  2.Patients who meet 1997 or 2019 SLE classification criteria ;

  3.Positive LA /ACL/ aβ2GPI ,on two or more occasions, at least 12 weeks apart;

  4.with at least one extra-criteria manifestations of APS, including thrombocytopenia, hemolytic anemia, nephropathy, valve heart disease ,skin ulcer and arterial or deep vein thrombosis;

  5.Maintain a stable base treatment regimen for at least 4 weeks before screening; Basic treatment includes anticoagulants/antiplatelet agents, glucocorticoids, and hydroxychloroquine;

  6.No response, intolerance or dependence on glucocorticoids and immunosuppressants;

  7.Patients who had previously used beliumab or Telitacicept could be enrolled in the study after 12 weeks of discontinuation;

  8.Age ≥18 years;

  9.Signed Informed consent.

Exclusion Criteria:

• 1.Patients with other causes of thrombocytopenia, hemolytic anemia, valvular heart disease, kidney disease and skin ulcer symptoms were excluded, such as drugs, infections, blood system diseases, genetic metabolic diseases, etc;

  2.Severe cardiovascular diseases, kidney, liver and other important organ injuries, serious blood and endocrine system lesions (aplastic anemia, hyperthyroidism crisis, etc.) were excluded; A history of active malignancy (within 5 years) was excluded and chemoradiotherapy was performed; Patients with organ or bone marrow transplantation in the past year were excluded. Exclusion of mentally ill persons;

  3.A history of allergy to the relevant test drug;

  4.Patients had recently received a live vaccine or planned to use any live vaccine during the study;

  5.Ongoing pregnancy;

  6.Patients who were participants in clinical trials of other immunosuppressive agents/biologics within 24 weeks;

  7.Other conditions that the investigator considers would make the candidate unsuitable for the study;

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
RTX+TA group; Screening stage：Patients received 200mg of rituximab intravenously at week 0 and week 2. Follow-up period：Telitacicept 160mg once a week for 24 weeks Basic treatment： Hydroxychloroquine、Prednisone、Warfarin、Aspirin	Drug: Telitacicept; 160mg once a week for 24 weeks; Other Names: TA; Drug: Rituximab; Patients received 200mg of rituximab intravenously at week 0 and week 2.; Other Names: RTX; Drug: Aspirin; 50-100mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response; Other Names: Asp; Drug: Warfarin; Warfarin should be used in patients with arterial thrombosis, and rivaroxaban should be replaced if the patient cannot reach the standard or cannot tolerate it; Other Names: WF; Drug: Hydroxychloroquine; 200mg, po, twice per day (Bid) prescribed，if tolerated by the patient， the dose should remain constant during the observation period; Other Names: HCQ; Drug: Prednisone; 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response; Other Names: Pred
RTX group; Screening stage：Patients received 200mg of rituximab intravenously at week 0 and week 2. Follow-up period Basic treatment：Hydroxychloroquine、Prednisone、Warfarin、Aspirin	Drug: Rituximab; Patients received 200mg of rituximab intravenously at week 0 and week 2.; Other Names: RTX; Drug: Aspirin; 50-100mg, po, once per day (Qd) prescribed if needed and adjusted due to patient response; Other Names: Asp; Drug: Warfarin; Warfarin should be used in patients with arterial thrombosis, and rivaroxaban should be replaced if the patient cannot reach the standard or cannot tolerate it; Other Names: WF; Drug: Hydroxychloroquine; 200mg, po, twice per day (Bid) prescribed，if tolerated by the patient， the dose should remain constant during the observation period; Other Names: HCQ; Drug: Prednisone; 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response; Other Names: Pred

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients who achieved response(complete response and partial response) in aPL profiles	For the lupus anticoagulant (LAC) test, we defined complete response (CR) as a negative test result and no response(NR) as a positive test result； For the anticardiolipin antibody (aCL)/anti-β2 glycoprotein I (anti-β2GPI)enzyme-linked immunosorbent assay,CR was defined as a titer of<the 95th percentile, partial response (PR) was defined as a titer of 95th -99th , and NR was defined as a titer of >the 99th percentile.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients who achieved response(complete response and partial response) in aPL profiles	For the lupus anticoagulant (LAC) test, we defined complete response (CR) as a negative test result and no response(NR) as a positive test result； For the anticardiolipin antibody (aCL)/anti-β2 glycoprotein I (anti-β2GPI)enzyme-linked immunosorbent assay,CR was defined as a titer of<the 95th percentile, partial response (PR) was defined as a titer of 95th -99th , and NR was defined as a titer of >the 99th percentile.	Week 24,48
The change of aPL titer	titer change of lupus anticoagulant, anticardiolipin antibody and anti-β2 glycoprotein-I antibody	week 12 , 24,48
The changes of the positive number of 7 aPL indicators	Change in the number of antibody positives.	week 12, 24,48
The change of clinical efficacy in subgroups with different symptoms	Thrombocytopenia, haemolytic anemia, nephropathy, heart valve lesions, skin changes (livedo reticularis, leg ulcers)	Before the screening,baseline and week 12,24,48
The change of aGAPSS score	The aGAPSS was calculated by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-β2 glycoprotein-I antibodies and four for positive lupus anticoagulant test.	Before the screening,baseline and week 12,24,48
The change of Damage Index for Antiphospholipid Syndrome (DIAPS)	The score is obtained by adding the output rating for each domain. The instrument demonstrated content, criterion, and construct validity being a precise tool to quantify organ damage in APS.	Before the screening and week 12,24,48
The change of Physician Global Assessment (PGA) score .	PGA is a physician-reported visual analogue scale that provides an overall meas- ure of the subject's current disease activity,the PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity;	Before the screening,baseline and week 12,24,48
The change of Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k) Score	The SLEDAI-2K is an established, validated SLE activity index. It is based on the presence of 24 features in 9 organ systems and measures disease activity in SLE patients in the previous 10 days.	Before the screening,baseline and week 12,24,48
The percentage of patients with Lupus Low Disease Activity State (LLDAS)	LLDAS is defined as: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.	Before the screening,baseline and week 12,24,48
Glucocorticoid (GC) dose and reduction rate	The proportion of patients who received the GC dose at each time point	Before the screening,baseline and week 4,12,24,48

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of participants experiencing adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Before the screening,baseline and week 4,12,24,48

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Investigators: Study Director: Yang Xiaoyun, Dr., Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): December 30, 2025
• Study Completion (Anticipated): December 30, 2025

Study Registration Dates

• First Submitted: November 17, 2022
• First Submitted That Met QC Criteria: November 30, 2022
• First Posted (Estimate): December 9, 2022

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: November 30, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Rituximab; Telitacicept
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Antiphospholipid Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Anticoagulants; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Aspirin; Rituximab; Prednisone; Warfarin; Hydroxychloroquine
• Other Study ID Numbers: Bioagents in APS QiluH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No