Belimumab After Rituximab in Resistant Primary Juvenile SS

NCT06410833 | Recruiting Phase 4

• 1 other identifier: K3926
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Sjogren's Syndrome; Pediatric ALL

Keywords

Rituximab; Belimumab

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change From Baseline in European League Against Rheumatism (EULAR) Sjogren's Syndrome Disease Activity Index (ESSDAI) at Week 28

  week 0 and 28

• Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) at Week 28

  week 0 and 28

• the Sjögren's Tool for Assessing Response (STAR)

  week 28

• Schirmer test

  Week 0 and 28

• salivary flow rate

  week 0 and 28

Study Arms (1)

sequential use of rituximab and belimumab

EXPERIMENTAL

Drug: Rituximab; Drug: Belimumab

Interventions

Rituximab DRUG

Rituximab weekly until B%\<0.5% or B#\<20×10\^6/L

sequential use of rituximab and belimumab

Belimumab DRUG

Belimumab every four weeks

sequential use of rituximab and belimumab

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 5-18 years old.
• Meets SS diagnostic AECG criteria or Japan criteria.
• 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
• Agree to receive the treatment of rituximab combined with belimumab

You may not qualify if:

• Previously treated with rituximab within six months, or previously treated with other biologics, including belimumab or Telitacicept
• Participate in other clinical trials within 6 months
• eGFR\<30ml/min
• 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.
• 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).
• Primary immunodeficiency
• History of malignant neoplasm
• 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
• Comorbidities not SS related currently requiring systemic corticosteroid therapy.
• Within 10 days before the first administration of Belimumab, IgG\<4g/L or IgA\<0.1g/L
• WBC\<1.5 × 109/L within 10 days before the first administration of Belimumab or neutrophils\<1 × 109/L

Sponsors & Collaborators

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

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Conditions

Sjogren's Syndrome; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Rituximab; belimumab

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Zhou

CONTACT

+86 01069156251; yzhou11@tsinghua.org.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 29, 2024
• First Posted: May 13, 2024
• Study Start: March 9, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 16, 2024

Record last verified: 2024-05

Locations

CN (1)