RITUXIMAB for Granulomatous lymphocytic interstitial lung disease (GLILD)

Inclusion criteria

• {"criterion_text":"- Age between 18-70 years, inclusive at the time of signing the informed consent.\n- Body weight within 50-130 kg.\n- Fulfilment of the Europen Society of Immunodeficiencies (ESID) 2019 diagnostic criteria for Common Variable Immunodeficiency (CVID).\n- 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.\n- Disease progression as defined as follows: •\tAn absolute decrease of >10 p.p. in % of predicted DLCO within the last 12 months combined with increasing* HRCT findings. OR •\tDLCO 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 •\tDLCO between 50% and 70% of predicted value.\n- 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.\n- 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.\n- The participant must be capable of giving signed informed consent."}

Exclusion criteria

• {"criterion_text":"- DLCO <50% of predicted.\n- Inadequate IgG substitution therapy during last 3 months.\n- History of Progressive Multifocal Leukencephalopathy (PML).\n- Known hypersensitivity to rituximab or murine proteins.\n- Known previous significant adverse reaction or side effect to rituximab treatment.\n- Neutrophil count < 1.0 x 109/L.\n- CD4+ T-cell count < 200 x 106/L.\n- The participant is on current or recent immune modulating treatment for any condition, defined as one or more of the following: a.\tLast dose of rituximab (or other anti-CD20 mAbs) < 2 years before enrollment. b.\tTreatment with corticosteroids doses equivalent to ≥ 7,5 mg prednisolone daily for more than 7 days within the three last months. c.\tMaintenance treatment with > 5 mg prednisolone (or equivalent dose of any other corticosteroid) daily. d.\tOther 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.\n- The participant is currently enrolled in another therapeutic trial.\n- The participant is pregnant (a negative pregnancy test is required) or planning pregnancy during the next 2 years.\n- Presence of active malignancy.\n- FVC < 50% of predicted.\n- Presence of any hematological malignant disease (deemed cured or not) during the last 5 years.\n- Life expectancy less than 12 months.\n- Other conditions that the investigators agree upon contraindicate participation.\n- The participant has predominantly fibrotic features on HRCT.\n- The participant is currently in recovery, defined as: a.\tDLCO improvement of ≥ 10 p.p. of predicted value within the last 12 months (if previous measurements are available). OR b.\tSignificant improvement of HRCT findings over the last 12 months (if previous HRCTs are available).\n- 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.\n- HIV infection.\n- Chronic or latent hepatitis B or C infection.\n- Active or latent tuberculosis.\n- Concomitant other chronic or acute systemic infection."}

Primary endpoints

• {"endpoint_text":"- DLCO (expressed in p.p. of predicted DLCO value) at Week 27 (continuous).","definition_or_measurement_approach":"Diffusion capacity of the lung for carbon monoxide (DLCO) expressed in percentage points of predicted DLCO value measured at Week 27 (continuous outcome)."}

Secondary endpoints

• {"endpoint_text":"- DLCO (expressed in p.p. of predicted DLCO value) at baseline, Week 13, 53 and 78 (continuous).","definition_or_measurement_approach":"DLCO measured at baseline and Weeks 13, 53 and 78, expressed in percentage points of predicted DLCO (continuous)."}
• {"endpoint_text":"- Reaching a 10 p.p. increase in % of predicted DLCO from baseline to Week 27 (dichotomous).","definition_or_measurement_approach":"Proportion of participants achieving ≥10 percentage point increase in predicted DLCO from baseline to Week 27 (yes/no, dichotomous)."}
• {"endpoint_text":"- FVC (expressed in p.p. of predicted FVC value) at Week 13, 27, 53 and 78 (continuous).","definition_or_measurement_approach":"Forced vital capacity (FVC) measured at Weeks 13, 27, 53 and 78, expressed in percentage points of predicted FVC (continuous)."}
• {"endpoint_text":"- Reaching a 5 p.p. increase in % of predicted FVC from baseline to Week 27 (dichotomous).","definition_or_measurement_approach":"Proportion of participants achieving ≥5 percentage point increase in predicted FVC from baseline to Week 27 (dichotomous)."}
• {"endpoint_text":"- HRCT ILD score at baseline, Week 27 and 53 (continuous).","definition_or_measurement_approach":"High-resolution CT interstitial lung disease score assessed at baseline, Week 27 and Week 53 (continuous)."}
• {"endpoint_text":"- King’s Brief Interstitial Lung Disease (K-BILD) Questionnaire scores (total and per domain) at baseline and Week 27 (continuous).","definition_or_measurement_approach":"Patient-reported outcomes using K-BILD questionnaire total and domain scores at baseline and Week 27 (continuous)."}
• {"endpoint_text":"- Short Form 36 Health Survey (SF-36) scores (total and per domain/concept) at baseline and Week 27 (continuous).","definition_or_measurement_approach":"Patient-reported health-related quality of life measured by SF-36 total and domain scores at baseline and Week 27 (continuous)."}
• {"endpoint_text":"- Serum levels of sCD25, sTIM3, BAFF and sBCMA at baseline, Week 13, 27 and 53 (continuous).","definition_or_measurement_approach":"Biomarker measurements (serum sCD25, sTIM3, BAFF, sBCMA) at baseline and Weeks 13, 27 and 53 (continuous)."}

Denmark

Earliest CTIS Part Ii Submission Date

04-06-2025

Latest Decision Or Authorization Date

10-06-2025

Processing Time Days

6

Number Of Sites

2

Number Of Participants

10

Norway

Earliest CTIS Part Ii Submission Date

02-05-2025

Latest Decision Or Authorization Date

09-06-2025

Processing Time Days

38

Number Of Sites

4

Number Of Participants

10

Finland

Earliest CTIS Part Ii Submission Date

11-05-2025

Latest Decision Or Authorization Date

09-06-2025

Processing Time Days

29

Number Of Sites

1

Number Of Participants

10

Sweden

Earliest CTIS Part Ii Submission Date

30-04-2025

Latest Decision Or Authorization Date

09-06-2025

Processing Time Days

40

Number Of Sites

2

Number Of Participants

10

Primary sponsor

Full Name

Oslo University Hospital HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"code 1","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"code 1","organisation_type":"Hospital/Clinic/Other health care facility"}