A randomized controlled phase II, double blinded trial to investigate pulmonary function after treatment with rituximab compared to placebo in patients with Granulomatous Lymphocytic Interstitial Lung Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

17 Dec 2025 → ongoing

Decision date (initial)

2025-06-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

KLINBEFORSK (Norwegian National Programme for Clinicial Research in Specialist Health Care)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To determine the effect of rituximab vs. placebo on diffusion capacity of the lung (DLCO) in Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) patients at Week 27.

Secondary objectives 5

1. To evaluate the effect of rituximab vs. placebo on DLCO in GLILD patients at Week 13, 53 and 78.
2. To evaluate the effect of rituximab vs. placebo on Forced Vital Capacity (FVC) in GLILD patients.
3. To evaluate the effect of rituximab vs. placebo on High Resolution Computed Tomography (HRCT) in GLILD patients.
4. To evaluate the effect of rituximab on Patient Related Outcomes as dyspnea and health-related quality of life.
5. To evaluate if rituximab affects levels of serum protein markers of lymphocyte activation.

Conditions and MedDRA coding

Granulomatous Lymphocytic Interstitial Lung Disease (GLILD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age between 18-70 years, inclusive at the time of signing the informed consent.
2. Body weight within 50-130 kg.
3. Fulfilment of the Europen Society of Immunodeficiencies (ESID) 2019 diagnostic criteria for Common Variable Immunodeficiency (CVID).
4. Diagnosis of GLILD by a consensus evaluation involving a clinician treating patients with primary immunodeficiency, a chest radiologist and a pulmonologist, based on radiological and clinical findings, with or without histological findings compatible with GLILD.
5. Disease progression as defined as follows: • An absolute decrease of >10 p.p. in % of predicted DLCO within the last 12 months combined with increasing* HRCT findings. OR • DLCO between 70 % and 80% of predicted value combined with increasing* HRCT findings (* compared to the most recent HRCT examination within the last 3 years). OR • DLCO between 50% and 70% of predicted value.
6. Other causes of pulmonary function decline and/or HRCT findings (including infection) are rendered unlikely based on blood inflammatory markers, serology, PCR and microbiological sampling from airways as appropriate.
7. Female participants of childbearing potential must be willing to use highly effective contraceptive measures during the study intervention period and 12 months after the last dose of IMP.
8. The participant must be capable of giving signed informed consent.

Exclusion criteria 22

1. DLCO <50% of predicted.
2. FVC < 50% of predicted.
3. The participant has predominantly fibrotic features on HRCT.
4. The participant is currently in recovery, defined as: a. DLCO improvement of ≥ 10 p.p. of predicted value within the last 12 months (if previous measurements are available). OR b. Significant improvement of HRCT findings over the last 12 months (if previous HRCTs are available).
5. Stage C or D heart failure according to 2022 AHA/ACC/HFSA Guidelines, unmanaged cardiac arrhythmia, unstable coronary heart disease or cardiomyopathy. All participants will be screened by questioning regarding symptoms, history of cardiac disease, ECG and measurement of NT-pro-BNPand troponin T. Echocardiography will be performed if needed for assessment.
6. HIV infection.
7. Chronic or latent hepatitis B or C infection.
8. Active or latent tuberculosis.
9. Concomitant other chronic or acute systemic infection.
10. Inadequate IgG substitution therapy during last 3 months.
11. History of Progressive Multifocal Leukencephalopathy (PML).
12. Known hypersensitivity to rituximab or murine proteins.
13. Known previous significant adverse reaction or side effect to rituximab treatment.
14. Neutrophil count < 1.0 x 109/L.
15. CD4+ T-cell count < 200 x 106/L.
16. The participant is on current or recent immune modulating treatment for any condition, defined as one or more of the following: a. Last dose of rituximab (or other anti-CD20 mAbs) < 2 years before enrollment. b. Treatment with corticosteroids doses equivalent to ≥ 7,5 mg prednisolone daily for more than 7 days within the three last months. c. Maintenance treatment with > 5 mg prednisolone (or equivalent dose of any other corticosteroid) daily. d. Other immune modulating treatment including (but not limited to) TNF inhibitor, abatacept, methotrexate, sirolimus and JAK inhibitor treatment with last dose administered < 6 months before enrollment.
17. The participant is currently enrolled in another therapeutic trial.
18. The participant is pregnant (a negative pregnancy test is required) or planning pregnancy during the next 2 years.
19. Presence of active malignancy.
20. Presence of any hematological malignant disease (deemed cured or not) during the last 5 years.
21. Life expectancy less than 12 months.
22. Other conditions that the investigators agree upon contraindicate participation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. DLCO (expressed in p.p. of predicted DLCO value) at Week 27 (continuous).

Secondary endpoints 8

1. DLCO (expressed in p.p. of predicted DLCO value) at baseline, Week 13, 53 and 78 (continuous).
2. Reaching a 10 p.p. increase in % of predicted DLCO from baseline to Week 27 (dichotomous).
3. FVC (expressed in p.p. of predicted FVC value) at Week 13, 27, 53 and 78 (continuous).
4. Reaching a 5 p.p. increase in % of predicted FVC from baseline to Week 27 (dichotomous).
5. HRCT ILD score at baseline, Week 27 and 53 (continuous).
6. King’s Brief Interstitial Lung Disease (K-BILD) Questionnaire scores (total and per domain) at baseline and Week 27 (continuous).
7. Short Form 36 Health Survey (SF-36) scores (total and per domain/concept) at baseline and Week 27 (continuous).
8. Serum levels of sCD25, sTIM3, BAFF and sBCMA at baseline, Week 13, 27 and 53 (continuous).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Børre Fevang

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Børre Fevang

Third parties 2

Locations

4 EU/EEA countries · 9 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 23 files

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

Application history

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