Ultimate dePletion of autoReactive b cells using Obinutuzumab from sjÖgren's syndrome affected Tissues study- UPROOT study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Radboud universitair medisch centrum Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Decision date (initial)

2026-03-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Roche

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy

To analyze if Obinutuzumab induces depletion of anti-nuclear antibody producing and rheumatoid factor B cells in affected tissues of patients with SjS.

Secondary objectives 3

1. to assess the potential clinical effect of Obinutuzumab in SjS patients.
2. to analyze the indirect effects of Obinutuzumab on other inflammatory cell populations in affected tissues.
3. to assess the effects of Obinutuzumab on aberrant clonally expanded B cells in affected tissues.

Conditions and MedDRA coding

Sjögren's syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. - adult patients, age ≥ 18 years.
2. - patients with with primary SjS fulfilling the EULAR/ACR 2016 classification criteria
3. - Presence of ANA, anti-Ro60, anti-La.
4. - Cryoglobulinemia and/or previous predictors for development lymphoproliferative disease. These consist of at least one of the following: - detectable rheumatoid factor antibodies - a history of lymphadenopathy - a history of salivary gland swelling - a history of purpuric lesions or biopsy-proven vasculitis - a lymphocytic focus score ≥ 3 in a salivary gland biopsy performed for diagnosis or for screening.
5. - In female patients: use of reliable method of contraception during the study and at least until 18 months after the last injection, in women of child bearing potential.
6. - signed written informed consent.
7. - Willingness to undergo study procedures, including tissue biopsies as described in the informed consent.

Exclusion criteria 20

1. - presence of active concurrent inflammatory or infectious condition.
2. - positive serology for hepatitis B, C or Human Immunodeficiency Virus.
3. - positive pregnancy test or breast feeding.
4. - opportunistic infection in the preceding 3 months.
5. - Subjects with current clinical or laboratory evidence of active tuberculosis(TB).
6. - Subjects with a history of active TB treated within the last 3 years.
7. - Subjects with untreated latent TB
8. - heavy alcohol consumption (>3 drinks/day).
9. - liver cirrhosis or severe renal insufficiency.
10. - patients for whom Obinutuzumab is contra-indicated as described in the local label (SmPc).
11. - Necessity to immunize with live or attenuated viral vaccines during treatment with Obinutuzumab and until B-cell recovery.
12. - patients currently participating in any interventional clinical trials.
13. - previous experience with Obinutuzumab through a clinical trial or regular treatment
14. - concomitant use of any biologic DMARDs etanercept, adalimumab, infliximab, anakinra, abatacept, tocilizumab, certolizumab, golimumab) or targeted synthetic DMARDs tofacitinib, baracitinib or filgotinib or any classical DMARD.
15. - treatment with rituximab or any other anti-CD20 therapy < 9 months before inclusion. - In patients treated with rituximab or any other anti-CD20 therapy 9-12 months before inclusion: A CD19+ B-cell count in peripheral blood of < 80 cells/microliter.
16. - concurrent treatment with prednisone > 10 mg orally.
17. - change in prednisone dosage within 4 weeks before the baseline visit
18. - change in prednisone dosage within 4 weeks before the baseline visit
19. - treatment with intra-muscular, intra-articular or intravenous prednisone 4 weeks before the baseline visit.
20. - uncooperative or any condition that could make the patient potentially noncompliant to the study procedures, etc, and, as applicable in the Netherlands, individuals who are institutionalized due to regulatory or legal order.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Depletion of anti-Ro60, anti-Ro52, anti-La and rheumatoid factor B cells in blood, inflamed salivary gland and involved lymph node of patients with SjS at 3 months after initiation of Obinutuzumab compared to sampling before treatment initiation.

Secondary endpoints 7

1. - Change from baseline in ESSDAI score at Week 12, 24 and 36 (11).
2. - Proportion of patients achieving ≥3 points reduction from baseline in ESSDAIscore at Week 12, 24 and 36.
3. - Proportion of patients achieving ESSDAI<5 at Week 12, 24 and 36.
4. - Change from baseline in PhGA of disease activity at Week 12, 24 and 36
5. - Change from baseline in PaGA of disease activity at Week 12, 24 and 36.
6. - Proportion of patients achieving ≥ 1 point or 15% reduction from baseline in ESSPRI at Week 12, 24 and 36 (11).
7. 1. Change from baseline in STAR, Schirmer’s test, unstimulated whole saliva secretion

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Radboud universitair medisch centrum Stichting

Sponsor organisation

Radboud universitair medisch centrum Stichting

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Rogier Thurlings

Public contact point

Organisation

Radboud universitair medisch centrum Stichting

Contact name

Rogier Thurlings

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

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