A randomized, parallel-group, open-label, Phase IIb pilot trial to evaluate the effectiveness in reducing systemic disease activity with methotrexate compared with hydroxychloroquine in adult male and female participants with moderate-to-severe primary Sjögren’s disease (MOSAIC STUDY)

Trial details

Who runs it

Fondazione Policlinico Universitario Campus Bio-medico In Forma A Bbreviata Fon

Trial code

EU 2026-526767-38-00

Record updated

2026. október 15.

Original description

The primary objective of this study is to evaluate the comparative efficacy of methotrexate (MTX) versus hydroxychloroquine (HCQ) in reducing systemic disease activity in adult patients with moderate-to-severe primary Sjögren’s disease. This will be assessed by comparing the change in systemic disease activity, as measured by the ESSDAI score, between treatment groups from baseline to Week 74 (end of treatment period). The primary clinical question of interest is: What is the difference in mean change in ESSDAI score from baseline to Week 74 in adult patients with primary Sjögren’s disease treated with methotrexate compared with hydroxychloroquine, regardless of treatment discontinuation or use of concomitant therapies?Read full original descriptionShow less

The primary objective of this study is to evaluate the comparative efficacy of methotrexate (MTX) versus hydroxychloroquine (HCQ) in reducing systemic disease activity in adult patients with moderate-to-severe primary Sjögren’s disease. This will be assessed by comparing the change in systemic disease activity, as measured by the ESSDAI score, between treatment groups from baseline to Week 74 (end of treatment period). The primary clinical question of interest is: What is the difference in mean change in ESSDAI score from baseline to Week 74 in adult patients with primary Sjögren’s disease treated with methotrexate compared with hydroxychloroquine, regardless of treatment discontinuation or use of concomitant therapies?

Inclusion: Age ≥ 18 and < 75 years of age at the time of signing the informed consent form (ICF); Have a diagnosis of primary Sjögren’s disease and fulfill the 2016 ACR/EULAR Classification Criteria at the time of screening. Note: Classification may be confirmed using both historical documentation and assessments performed during the Screening Period; Have moderate to severe systemic disease activity as defined by an ESSDAI score ≥ 5 at screening; Are seropositive for anti-SSA/Ro antibodies at screening or documented in previous medical records; Have evidence of residual salivary gland function, defined as stimulated whole salivary flow > 0.1 mL/min; If receiving treatment for primary Sjögren’s disease, are on a stable therapeutic regimen prior to screening and are expected to remain on a stable dose during the study, unless modification is required for safety reasons; Are able and willing to provide written informed consent and comply with study procedures; Female participants of childbearing potential agree to use highly effective contraception during the study and for an appropriate period after the last dose of study treatment.

Exclusion: Have received live attenuated vaccines within 4 weeks prior to screening or are expected to receive them during the study; Have participated in another interventional clinical trial within 30 days prior to screening; Are receiving prohibited immunosuppressive or biologic therapies or have received high-dose corticosteroids (≥ 15 mg/day prednisone equivalent) within 6 weeks prior to randomization; Have a diagnosis of other systemic autoimmune diseases that may interfere with the assessment of primary Sjögren’s disease; Clinically significant pre-existing interstitial lung disease (ILD) or active pulmonary fibrosis of any etiology, including Sjögren-associated ILD requiring ongoing immunosuppressive or antifibrotic therapy, as determined by clinical history, chest imaging, or pulmonary function testing; History of methotrexate-induced pneumonitis or other drug-induced hypersensitivity pneumonitis attributed to methotrexate; Hepatitis B virus (HBV) infection, defined as a positive Hepatitis B surface antigen (HBsAg) result. Participants who are HBsAg-negative but Hepatitis B core antibody (HBcAb)-positive are eligible only if HBV DNA by quantitative PCR is undetectable at screening, subject to HBV DNA monitoring every 12 weeks during the treatment period; Have any condition that, in the opinion of the Investigator, would compromise participant safety or interfere with study assessments; Have a history of lymphoproliferative disease or active malignancy (with the exception of adequately treated non-invasive malignancies); Have clinically significant cardiovascular, pulmonary, renal, or neurological disease that may interfere with study participation or outcome assessment; Have active or severe infection, including chronic or recurrent infections, or positive screening for HIV, hepatitis B or C, or tuberculosis; Have known hypersensitivity or contraindications to methotrexate or hydroxychloroquine; Active hepatitis C virus (HCV) infection, defined as a positive HCV antibody result with detectable HCV RNA by quantitative PCR. Participants with a documented Sustained Virological Response (SVR) following antiviral treatment, or spontaneous viral clearance, confirmed by undetectable HCV RNA at screening, are eligible; Have clinically significant laboratory abnormalities at screening (including but not limited to liver dysfunction, cytopenias, or impaired renal function); Presence or history of clinically significant maculopathy, retinopathy of any etiology (e.g., age-related macular degeneration, diabetic retinopathy, hereditary retinal dystrophies), or other clinically significant retinal disorder that could either confound the assessment of hydroxychloroquine-associated ocular toxicity or increase the participant’s baseline risk of visual impairment, as determined at the baseline ophthalmological examination described in Section 8.4.7; Are pregnant or breastfeeding, or planning pregnancy during the study period.

EU CTIS 2026-526767-38-00