Rituximab and obinutuzumab 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] - 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

2024-518965-85-00

EudraCT number

2022-004335-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary goal of this study is to investigate the potential differential effects of RTX and OBI on the composition of lymph nodes and other target organs (i.e. skin and/or kidney) as well as (subsets of) immune cells in the peripheral blood. In addition, we will identify immunological alterations in lymphoid tissue and inflamed skin and/or kidney tissues of SLE patients and to correlate these alterations with disease stage/phenotype, prognosis, and 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. Inclusion criteria: SLE patients who: 1. fulfill ACR 1997 and/or SLICC and/or ACR/ EULAR 2019 criteria 2. have a SLEDAI-2K score ≥6 3. are aged between 18-75 4. are clinically determined to have severity of disease and refractoriness that supports the off-label use of anti-CD20 therapy

Exclusion criteria 1

1. Exclusion criteria Patients who are not able to give informed consent.  Pregnancy  Severe renal impairment (eGFR <30ml/min/1.73m2 according to CKD-EPI formula)  Present or previous treatment with any cell depleting therapies, including anti-B-cell therapy, belimumab or other investigational agents (e.g., abetimus sodium, anti CD40L antibody, BG9588/ IDEC 131) in the last 3 years. Investigational agent applies to any drug not approved for sale in the country in which it is being used.  90 days prior to anti-CD20 therapy: • Intravenous cyclophosphamide  30 Days Prior to anti-CD20 therapy (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 anti-CD20 therapy  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 proportion of patients with depletion of total CD19+ B cells in the peripheral blood (quantitative using highly-sensitivity flow cytometry) and lymph nodes, defined as a decrease of >2 points on a 4-point semi-quantitative scale. These will be separate co-primary endpoints. We will statistically test the difference in the proportions of patients with depletion by these criteria in RTX- versus OBI-treated patients,

Secondary endpoints 1

1. Correlation between CD19+ lymphocyte (and other B lineage cells) depletion in peripheral blood/tissues and clinical response. Depletion (defined as a decrease of >2 points on a 4-point semi-quantitative scale of CD19+ cells in the lymph node) 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 20 patients. Changes in B lineage cells and associated T cell subsets in lymph nodes and skin of SLE

Investigational products

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

Test 2

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 5 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