Belimumab in SLE

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Immune System Diseases [C20]

Trial duration

25 Nov 2024 → ongoing

Decision date (initial)

2024-11-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518966-28-00

EudraCT number

2022-000321-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary goal of this study is to investigate the effects of belimumab on the composition of lymph nodes and the inflamed synovial tissue as well as (subsets of) immune cells in the peripheral blood. In addition, we will identify immunological alterations in lymphoid tissue and inflamed synovial tissue of SLE patients and to correlate these alterations with disease stage/phenotype, prognosis, and belimumab treatment response. We thereby aim to identify and validate novel biomarkers that can be used for personalized medicine in SLE.

Conditions and MedDRA coding

Systemic lupus erythematodes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1.  SLE patients who: 1. fulfill ACR 1997 and/or SLICC and/or ACR/ EULAR 2019 criteria 2. have a SLEDAI-2K score ≥6 3. active joint disease (arthritis) in wrist, knee or ankle joints (optional) 4. are aged between 18-75 5. start with belimumab For comparison reasons, we will also include 5 SLE patients who do not start belimumab but receive intensified treatment with other drugs (i.e. steroids or DMARDs) to discriminate belimumab-specific effects from general immunosuppressive effects. Patients are allowed to use stable dosages or concomitant medication such as hydroxychloroquine, azathioprine, and/or low dose steroids (<10 mg), as well as medication of therapeutic classes other than immunosuppressants. All patients will be counseled to use appropriate contraceptive measures as is done routinely in clinical care when prescribing these type of medications

Exclusion criteria 1

1.  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 (e.g., abetimus sodium, anti CD40L antibody, BG9588/ IDEC 131). Investigational agent applies to any drug not approved for sale in the country in which it is being used.  90 days prior to belimumab: • Intravenous cyclophosphamide  30 Days Prior to belimumab (or 5 half-lives, whichever is greater) • Any non-biologic investigational agent. Investigational agent applies to any drug not approved for sale in the country in which it is being use  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 infection: • Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria) • Hospitalization for treatment of infection within 60 days of Day 0. • Use of parenteral (IV or IM) antibiotics (anti-bacterial, antiviral, anti-fungal, or anti-parasitic agents) within 60 days of Day 0  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 a history of a primary immunodeficiency, including significant IgG deficiency (IgG level < 400 mg/dL) or IgA deficiency (IgA level < 10 mg/dL)  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  Hepatitis status: • Serologic evidence of current or past Hepatitis B (HB) infection based on the results of testing for HBsAg and HBcAb as follows: patients positive for HBsAg or HBcAb are excluded • Positive test for Hepatitis C antibody  Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies  Have any other clinically significant abnormal laboratory value in the opinion of the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. the change in the composition of B lineage cells in the peripheral blood and lymph nodes. These will be separate co-primary endpoints. We will investigate the differences between SLE patients treated with belimumab compared to SLE patients treated with other drugs, expecting a more profound effect in patients treated with belimumab.

Secondary endpoints 1

1. Correlation between changes in B lineage cells in peripheral blood/tissues and clinical response. Alterations in the B cell lineage will be related to clinical response (defined as a >4 point improvement in cSLEDAI or any improvement in BILAG-2004 score) in a 2x2 chi-square test for all patients. Further secondary and exploratory outcomes are changes in B lineage cells and associated (pathogenic) T cell subsets in lymph nodes of SLE patients in comparison to the changes in the peripheral blood

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Sander Tas

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Sander Tas

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications