Belimumab After Rituximab in Resistant Primary Juvenile SS (BRRPJS)

Effectiveness of Belimumab After Rituximab in Resistant Primary Juvenile Sjogren's Syndrome

The goal of this clinical trial is to explore the effectiveness of sequential use of rituximab and belimumab in the treatment of resistant primary juvenile Sjogren's syndrome.

Does sequential use of rituximab and belimumab reduce the activity of SS in resistant patients

Researchers will compare the disease activity before and after the treatment of sequential use of rituximab and belimumab to see if the therapy works to treat SS.

Participants will:

Recieve Rituximab each week for 2-4 times until B%<0.5% or B#<20×10^6/L Recieve Belimumab 4 weeks after the last use of Rituximab, and then every 4 weeks until week 28

Study Overview

• Status: Recruiting
• Conditions: Pediatric ALL; Sjogren's Syndrome
• Intervention / Treatment: Drug: Rituximab; Drug: Belimumab

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zhou; Phone Number: +86 01069156251; Email: yzhou11@tsinghua.org.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Hongmei Song, Doctor; Phone Number: +86-10-69156271; Email: songhm1021@hotmail.com
      • Principal Investigator: Hongmei Song, Doctor
      • Contact: Zhou; Phone Number: +86 01069156251; Email: yzhou11@tsinghua.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 5-18 years old.
2. Meets SS diagnostic AECG criteria or Japan criteria.
3. classification for "resistant patients": Application of two or more immunosuppressants or prednisone +immunosuppressive therapy for more than 3 months. One of the following conditions still exists: a) systemic involvement: polyarthritis, vasculitis, autoimmune cytopenia or involvement of skin, kidney, lung, nerve, and liver. b) constituted B cell activation: elevated IgG, light chain, high β 2MG, C4 decrease, cryoglobulinemia, monoclonal antibody c) sustained increased inflammatory markers, such as ESR
4. Agree to receive the treatment of rituximab combined with belimumab

Exclusion Criteria:

1. Previously treated with rituximab within six months, or previously treated with other biologics, including belimumab or Telitacicept
2. Participate in other clinical trials within 6 months
3. eGFR<30ml/min
4. Active infections, including but not limited to: -- Current or past infection with hepatitis B or C as defined by: Hepatitis B surface antigen positive. Hepatitis B surface antibody positive and hepatitis B core antibody positive. Hepatitis C antibody positive. -- Historically positive HIV test or test positive at screening for HIV. -- Active tuberculosis.
5. Infection history: -- Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria) -- Hospitalisation for treatment of infection within 60 days of Day 0. -- Use of parenteral (intravenous or intramuscular) antibiotics (anti-bacterials, antivirals, anti-fungals or anti-parasitic agents) within 30 days of Day 0. -- Receipt of a live-attenuated vaccine within 3 months of Day 0. -- In the investigator's opinion, participants that are at high risk for infection (including but not limited to in dwelling catheter, dysphagia with aspiration, decubitus ulcer, history of prior aspiration pneumonia or recurrent severe urinary tract infection).
6. Primary immunodeficiency
7. History of malignant neoplasm
8. Severe, progressive or uncontrolled renal, hepatic, haematological, gastrointestinal, pulmonary, cardiac or neurological disease or, in the investigator's opinion, any other concomitant medical condition or significant abnormal laboratory value that places the participant at risk by participating in this trial with the exception of diseases or conditions related to active SS
9. Comorbidities not SS related currently requiring systemic corticosteroid therapy.
10. Within 10 days before the first administration of Belimumab, IgG<4g/L or IgA<0.1g/L
11. WBC<1.5 × 109/L within 10 days before the first administration of Belimumab or neutrophils<1 × 109/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sequential use of rituximab and belimumab	Drug: Rituximab; Rituximab weekly until B%<0.5% or B#<20×10^6/L; Drug: Belimumab; Belimumab every four weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respondence rate	In the context of the aforementioned criteria, a response is defined as the alteration of more than three of the following five indicators: a) Improvement of physician global assessment score by ≥30% b) Decrease in erythrocyte sedimentation rate (ESR) by ≥30% or normalization c) Improvement of B cell activation markers (IgG, RF) by ≥25% d) Improvement of lacrimal gland function: Improvement of Schirmer test by ≥5mm e) Improvement of salivary gland function: Increase in salivary flow rate by 25% or decrease in ultrasound score by ≥25%.	Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) at Week 28	The ESSDAI is a physician-administered tool designed to measure disease activity. It consists of 12 organ-specific 'domains' contributing to disease activity associated with the participant's Sjogren's Syndrome only (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. Overall score (ranges from 0 (no activity) to 123 (worst activity)) is calculated as sum of all individual weighted domain scores. A negative change from baseline value indicates improvement.	week 0 and 28
Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at Week 28	The ESSPRI is a participant-reported questionnaire to assess subjective participant symptoms and includes 3 domains (dryness, pain, and fatigue). Each domain is scored on scale of 0-10 (0 = no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. Minimum score can be 0 and maximum score can be 10. A negative change from baseline value indicates improvement.	week 0 and 28
the Sjögren's Tool for Assessing Response (STAR)	The STAR is a composite responder index that includes 5 items, and the score is from 0 to 9, while more than 5 points means improvement.	week 28
Schirmer test	Schirmer test is a assay to detect the production of tears and less than 5mm means abnormal.	Week 0 and 28
Score of salivary ultrasounds	The Hocevar scoring system was used investigating (1) parenchymal echogenicity compared with the thyroid gland, graded 0-1; (2) homogeneity, graded 0-3; (3) presence of hypoechogenicareas, graded 0-3; (4) hyperechogenic reflections, graded 0-3 in parotid glands and 0-1 in submandibular glands; and (5) clearness of the salivary gland border, graded 0-3, in both parotid and submandibular salivary glands. Total ultrasound score was the sum of these five domains and can range from 0 to 48. A higher score usually represents more severe disease.	week 0 and 28
salivary flow rate	Salivary flow rate is measured by unstimulated whole saliva. A higher salivary flow rate represents lower disease activity.	week 0 and 28

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Shengjing Hospital; The Affiliated Hospital of Qingdao University; Children's Hospital of Fudan University; Shanghai Children's Hospital; The First Hospital of Jilin University; Central South University; Shenzhen Children's Hospital; Children's Hospital of Chongqing Medical University; Children's Hospital of Nanjing Medical University; Tianjin Children's Hospital; Children's Hospital of The Capital Institute of Pediatrics

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 29, 2024
• First Submitted That Met QC Criteria: May 7, 2024
• First Posted (Actual): May 13, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Rituximab; Belimumab
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab; Belimumab
• Other Study ID Numbers: K3926

Drug and device information, study documents

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