Belimumab in SLE Synovial Inflammation and Lymph Nodes

NCT06327724 | Recruiting FDA Drug

• 1 other identifier: 12434
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Systemic lupus erythematosus (SLE)is an immune-mediated inflammatory disease (IMIDs) of which the cellular and molecular alterations of the immune system driving the diseases still remains largely unknown. Accordingly, it remains difficult to predict the individual patient's response to treatment. Moreover, the patient's response to treatment remains heterogeneous and difficult to predict, despite the development of a variety of novel and powerful drugs (including the so-called biologicals). Therefore, there is a clear need for the identification and validation of cellular and molecular biomarkers which can provide useful clinical information for diagnosis, classification, prognosis and treatment, as well as the development of new therapeutic strategies. Biomarkers can be found and analyzed in different body compartments, of which the peripheral blood and the intra-articular synovial fluid or tissue are most easily accessible. However, previous studies in RA and other IMIDs showed that adaptive immune responses in other tissues such as lymph nodes also play an important role. Investigating other immune compartments of the body such as the lymph nodes could result in new insights. To study the early pathogenesis of inflammatory conditions, in 2008 our department initiated core-needle inguinal lymph node biopsy sampling. Since then more than 100 lymph node biopsy procedures were performed. The procedure is well-tolerated and, other than a small hematoma which does not require therapy in most of the cases, no complications were reported. In the current study, the effects of belimumab (anti-BAFF) in SLE will be investigated by studying the immune alterations taking place in lymph nodes in comparison to peripheral blood and immune alterations taking place in the end-organ, e.g. the joint (wrist, knee or ankle) by taking synovial biopsies during a needle- or mini-arthroscopy. This procedure has been performed frequently in our department over the last 15 years. In this way immune alterations in the lymph nodes (secondary lymphoid organ), peripheral blood (systemic) and the joint (end organ for the disease) will be assessed and compared.

Conditions

Systemic Lupus Erythematosus

Keywords

lymph node; synovial tissue

Outcome Measures

Primary Outcomes (1)

• Differences in lymph node cellular composition as assessed by advanced flow cytometry

  Differences in lymph node cellular composition and functional aspects in SLE patients after belimumab treatment compared to SLE patients starting any other effective treatment.

  4 weeks

Secondary Outcomes (2)

• Differences in peripheral blood cellular composition as assessed by advanced flow cytometry

  4 weeks

• Differences in synovial tissue cellular composition as assessed by advanced flow cytometry

  4 weeks

Interventions

Belimumab DRUG

Start of new treatment due to active disease

Also known as: Any other treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

SLE patients

You may qualify if:

• SLE patients who:
• fulfill ACR 1997 and/or SLICC and/or ACR/ EULAR 2019 criteria,
• have active joint disease (arthritis) in wrist, knee or ankle joints.
• have a SLEDAI-2K score ≥6.
• are aged between 18-75
• start with belimumab or any other immunosuppressive treatment

You may not qualify if:

• Patients who are not able to give informed consent.
• Pregnancy
• Severe renal impairment (eGFR \<30ml/min/1.73m2)
• Active nephritis
• Present or previous treatment with any cell depleting therapies, including anti-B-cell therapy or other investigational agents
• Intravenous cyclophosphamide 90 days prior to belimumab
• Any non-biologic investigational agent 30 Days Prior to belimumab (or 5 half-lives, whichever is greater)
• Live vaccines within 30 days prior to baseline or concurrently with belimumab
• Presence of any other disease for which study subjects need chronic or intermittent immunosuppressive therapy (e.g. prednisolon for COPD).
• History of malignancies neoplasm within the last 5 years except basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years
• Have any intercurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study, including evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, poses a significant suicide risk
• Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior to Day 0
• Have a historically positive HIV test or test positive at screening for HIV, or other immunodeficiency

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Amsterdam UMC; location Academic Medical Center

Amsterdam, 1100DD, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

PBMC Lymph node biopsy Synovial tissue biopsy

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

belimumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Sander W Tas, Prof. dr.

CONTACT

+31 20 56 67765; secr-reumatologie@amsterdamumc.nl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Study Record Dates

• First Submitted: March 13, 2024
• First Posted: March 25, 2024
• Study Start: September 1, 2023
• Primary Completion: January 1, 2025
• Study Completion: March 1, 2025
• Last Updated: March 25, 2024

Record last verified: 2024-03

Locations

NL (1)