Anti-B-cell therapy in RA-ILD

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

25 May 2026 → ongoing

Decision date (initial)

2026-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objective of this trial is to investigate if rituximab (RTX) is superior to placebo in preserving pulmonary function (% predicted forced vital capacity) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) on a stable conventional background RA therapy.

Secondary objectives 4

1. To compare efficacy of RTX versus placebo in the groups on ILD severity using other outcome measures a) pulmonary function (forced vital capacity (FVC) (mL), percent predicted diffusion capacity of the lung for carbon monoxide (%pDLCO), absolute change of 6-minute walking test (6MWT)), b) radiographic extent (visual assessment of ILD-affected lung volume by radiologist and by lung texture analysis), c) patient-reported lung disease activity, function and health-related quality of life (HRQoL) (questionnaires) at 24 and 48 weeks.
2. To compare efficacy of RTX versus placebo on RA disease control assessed by disease activity measures (erythrocyte sedimentation rate (ESR), clinical disease activity index (CDAI), disease activity scores based on 28 joints (DAS28), c-reactive protein (CRP) DAS28-CRP) and remission rates at 24 and 48 weeks.
3. Safety impact of treatment will be assessed and compared by the frequencies of adverse events (AE) and serious adverse events (SAE) as well as by morbidity and mortality between the RTX and placebo groups.
4. Exploratory objectives include sub-group analyses to compare efficacy of RTX versus placebo on pulmonary function (FVC) at 24 and 48 weeks in the study population grouped by a) radiographic ILD pattern (Usual interstitial pneumonia (UIP) vs non-UIP), b) baseline %pDLCO (≥60 vs <60), c) baseline clinical joint disease activity (remission or not) and d) by MUC5B genotype. Pre-defined and unbiased profiling of plasma biomarkers for ILD activity and for predicting response to RTX will be explored as well.

Conditions and MedDRA coding

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. The subject has given their written consent to participate in the trial.
2. The subject is an adult with rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) positive RA fulfilling the 2010 ACR/EULAR RA classification criteria.
3. The subject has radiographic signs of ILD (defined as non-dependent abnormalities in ≥5% of a lung zone (upper, middle or lower) including ground glass opacities, reticulations, lung distortion, traction bronchiectasis, honey combing and non-emphysematous cysts) on a chest high resolution computed tomography (HRCT) scan (reviewed and concluded by two thoracic radiologists in consensus).
4. The subject has pulmonary function ≥ 50 %pFVC and 40-80 %pDLCO. Participants may be asymptomatic or symptomatic with respect to ILD.
5. The subject has a stable background conventional synthetic (cs) disease modifying anti-rheumatic drug (DMARD) therapy with or without a low dose prednisone since ≥ 12 weeks prior to baseline.

Exclusion criteria 19

1. Subjects with other chronic rheumatic disease, except for secondary Sjögrens syndrome.
2. Subjects with previous treatment with anti-B cell targeted therapy for RA.
3. Subjects with hypersensitivity towards murine proteins or excipients of rituximab drugs.
4. Subjects with inborn error of immunity or acquired severe immunodeficiency including but not limited to total immunoglobulin G < 6g/L.
5. Subjects with active infection (excluding fungal infections of nail beds) requiring hospitalization and/or i.v. anti-infectives ≤ 4 weeks, or oral anti-infectives* ≤ 2 weeks prior to baseline. *Prophylactic anti-viral therapy for chronic Hepatitis B and valaciclovir for Herpes Simplex type 2 are exempt (see exclusion criteria 6 and 7).
6. Subjects with a history of severe infection(s) including but not limited to disseminated and/or recurrent severe Herpes Simplex or Herpes Zoster infections.
7. Subjects with chronic hepatitis B without proper prophylactic therapy. Subjects with chronic hepatitis B can be included only if monitored with Hepatitis B DNA, aminotransferases (ALT and AST) every 12 weeks and treated with anti-viral drug for at least 7 days before RTX infusion and for at least 18 months after last RTX infusion.
8. Subjects with suspected or diagnosed active or latent tuberculosis and/or positive QuantiFERON (or TB-spot) test. Subjects with latent tuberculosis can be included if successfully treated or have initiated prophylaxis therapy ≥ 1 months of baseline.
9. Subjects with biologic or targeted synthetic DMARDs, anti-fibrotic therapy or cyclophosphamide ≤ 12 weeks prior to baseline.
10. Subjects with a history of malignancy ≤ 5 years prior to baseline (except for successfully treated cervical carcinoma in situ, basal cell and squamous cell carcinoma of the skin, with no evidence of recurrence or metastatic disease for at least 3 years).
11. Subjects with severe congestive heart failure (NYHA class 4) or severe uncontrolled heart disease.
12. Subjects with asthma or COPD with FEV1/FVC < 0.7.
13. Subjects with any significant comorbidity or disorder (including clinically significant pathological lab results) that according to the investigator will preclude study participation.
14. Subjects with any other factors (such as significant psychiatric or mental disorder, alcohol or other substance abuse, language barriers) that will make adherence to the protocol difficult.
15. Women of childbearing potential i.e. any female who has experienced menarche and does not meet the criteria for "women not of childbearing potential” defined as: women who are postmenopausal (12 months with no menses without an alternative medical cause) or who are permanently sterilized (e.g. hysterectomy, bilateral oophorectomy, or bilateral salpingectomy)) not willing or able to use highly effective methods of birth control (resulting in a low failure rate of less than 1% per year when used consistently and correctly) from 14 days prior to IMP administration, throughout the duration of the study and up to 6 months after end-of-study (i.e. 12 months after last RTX/Placebo IMP dose).
16. Subject who is, or wish to become, pregnant or lactating during and ≤ 6 months after the study.
17. Subjects with current or recent (≤30 days prior to baseline) participation in a clinical trial with an investigational product.
18. Subjects with absolute neutrophil count <1.5 x10^9/L.
19. Subjects with absolute thrombocyte count <75 x10^9/L.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in mean absolute change of %pFVC from baseline to 48 weeks between RTX treatment and placebo (PBO) groups.

Secondary endpoints 20

1. Absolute change in FVC (mL) at 24 and 48 weeks.
2. Absolute change in %pDLCO (Hb-corrected) at 24 and 48 weeks.
3. Proportions of patients with absolute decline ≥5% in %pFVC at 48 weeks (definition of clinically meaningful progression).
4. Proportions of patients with ≥10% relative decline in %pFVC or ≥5 to <10% relative decline in %pFVC and ≥15% relative decline in %pDLCO at 48 weeks (OMERACT definition of progression).
5. Proportions of patients with stable (<5% absolute change) or improved FVC (%p and mL) at 48 weeks.
6. Time-to-event “progression ≥10% of %pFVC”.
7. Absolute change (in meters) of 6MWT at 48 weeks.
8. Absolute change in overall extent (% affected lung volume) of ILD-associated abnormalities (reticulations, ground glass, fibrosis, traction bronchiectasis, honey combing abnormalities) on HRCT of the lungs at 48 weeks by visual assessment of two radiologists with expertise in ILD.
9. Absolute change in overall (and separate entities) extent (volume) of ILD-associated abnormalities at 48 weeks by lung texture analysis based on CALIPER of HRCT scans.
10. Change in Health Assessment Questionnaire – disability index (HAQ-DI) at 24 and 48 weeks.
11. Change in total (and separate; breathlessness and activities, chest symptoms and psychological) score of King’s Brief Interstitial Lung Disease Questionnaire (K-BILD) at 24 and 48 weeks.
12. Change in total (and separate; physical and emotional) score of Dyspnea-12 Questionnaire (D-12) at 24 and 48 weeks.
13. Change in score on Short Form 36 (SF36) health survey at 24 and 48 weeks.
14. Change in Euro-Qol measure of HRQoL in 5 dimensions (EQ-5D) at 24 and 48 weeks.
15. Frequency of all-cause mortality and all-cause hospitalization during the trial.
16. Frequencies of adverse events (AE) and serious adverse events (SAE) during the trial.
17. Change from baseline in disease activity by swollen and tender joint counts, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), disease activity score based on 28 joints (DAS28), DAS28-CRP, clinical disease activity index (CDAI) and Physician’s/Patient’s Global Assessment (PhGA/PGA) of RA disease activity on VAS at 24 and 48 weeks.
18. Proportions of patients in DAS28-, CDAI- and ACR/EULAR Boolean 2.0 remission respectively at 48 weeks.
19. Subgroup analysis based on baseline ILD type, ILD severity, joint disease activity and by presence of the ILD-associated MUC5B genetic variant.
20. Change from baseline to 24 and 48 weeks of proposed ILD plasma biomarkers KL-6, surfactant protein-D, MMP-7 and CXCL10 as well as of unbiased plasma protein profiles.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vaenersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Sahlgrenska University Hospital, Department of Rheumatology

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Sahlgrenska University Hospital, Department of Rheumatology

Locations

1 EU/EEA country · 6 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

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