NCT04916756

A Prospective Pilot Study to Explore Efficacy and Safety of Baricitinib in Active Primary Sjogren's Syndrome Patients

Completed Phase 1, PHASE2 Last updated 30 June 2021

What this trial tests

Phase 1, PHASE2 trial testing Baricitinib 2 MG in Sjogren's Syndrome in 11 participants. Completed in 25 March 2021.

Timeline

16 January 2020

Primary endpoint
24 December 2020

25 March 2021

Quick facts

Lead sponsor	Peking Union Medical College Hospital
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	11
Start date	16 January 2020
Primary completion	24 December 2020
Estimated completion	25 March 2021
Sites	1 location across China

Drugs / interventions tested

• Baricitinib 2 MG — full drug profile →

Conditions studied

• Sjogren's Syndrome — all drugs for Sjogren's Syndrome →

Sponsor

Peking Union Medical College Hospital

Who can join

18 and older, any sex, with Sjogren's Syndrome. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Primary Sjogren's syndrome (pSS) is a systemic autoimmune disease characterized by dysfunction of the exocrine glands, which results in sicca symptoms in affected patients. JAK/STAT signaling pathway is activated and playing as a key pathway in the differentiation and activation of many lymphocytes, so that affect the pathogenesis of many autoimmune diseases including pSS. JAK inhibitors have also been widely used in the treatment of rheumatoid arthritis and other autoimmune diseases.

Some studies have confirmed that JAK/STAT pathway is activated in patients with pSS, and JAK inhibitor may be effective for pSS. Filgotinib, the selective JAK1 inhibitor, is one of the "secondary generation" JAK inhibitors developed these years. Lee et al. found that filgotinib suppressed the IFN-induced transcription of differentially expressed genes and BAFF in human primary salivary gland epithelial cells. In addition, filgotinib-treated mice exhibited increased salivary flow rates and marked reductions in the lymphocytic infiltration of SGs, indicating that JAK inhibitors may be a novel therapeutic approach for pSS. A randomized phase 2 study is currently in progress to assess the safety and efficacy of filgotinib in adult subjects with active Sjogren's syndrome. So far, there is no evidence of the safety and efficacy of baricitinib in patients with pSS.

Baricitinib, an oral inhibitor of JAK1/JAK2, was the second JAK inhibitor approved for clinical use in RA. It has been approved for the treatment for moderate to severe active RA in adult patients who have responded inadequately to, or are intolerant to, one or more disease-modifying anti-rheumatic drugs (DMARDs). The efficacy and safety of baricitinib in RA have been extensively evaluated in pre-clinical animal models of arthritis, as well as in clinical studies. There are also some reports of baricitinib used in other autoimmune diseases, such as systemic lupus erythematosus, dermatomyositis and PMR/GCA. In a double-blind, multicenter, randomized, placebo-controlled, 24-week phase 2 study across 11 countries, baricitinib treatment at a dose of 4 mg dose significantly improved the signs and symptoms of active SLE, with a high-resolution rate of 67% in SLEDAI-2K arthritis or rash, and showed a safety profile consistent with previous studies into baricitinib to treat RA. The study focused on specific organ manifestations, which benefited patients treated with baricitinib with rash and arthritis. So far, only one study has focused on the potential efficacy of baricitinib in SS. In that study, Aota et al. demonstrated baricitinib suppressed IFN-γ-induced CXCL10 expression in human salivary gland ductal cells and suggested its potential for the treatment of SS. Based on these, we thought that baricitinib might have therapeutic benefit in patients with pSS.

We plan to explore the efficacy and safety of baricitinib in patients with pSS in this single-center, prospective, open label, 24-weeks pilot study. We plan to enroll 11 patients diagnosed as active pSS in Peking Union Medical College Hospital, Beijing, China. They will be treated with baricitinib 2mg once a day for 24 weeks. We'll evaluate the disease activity mainly by ESSDAI and ESSPRI score. And we'll also record the adverse reactions. The primary endpoint of the study is the change of ESSDAI score at 12 weeks. The secondary endpoints include: the minimal clinically important improvement (MCII) of ESSDAI, which was defined as an improvement of ESSDAI of at least three points; the change of ESSDAI score at 24 weeks; the change of ESSPRI and PGA score at 12 and 24 weeks; and remissions of organ involvement at 12 and 24 weeks. The main inclusion criteria include: (1) ≥18 years old, (2) fulfill the criteria of the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification for primary SS, (3) with moderate or high activity of SS, which was defined as EULAR primary SS disease activity index (ESSDAI) ≥5, and (4) with serological activity defined as elevated C-reactive protein, erythrocyte sedimentation rate (ESR), and/or immunoglobulin G (IgG) level (excluding acute and chronic infection and other factors). The main exclusion criteria include: (1) patients diagnosed with an active central nervous system disease or dysfunction of a major organ (heart, liver, kidney); (2) pregnant or lactating women; (3) current severe infections; and (5) undergoing glucocorticoids or immunosuppressants treatment with stable dosage for less than 12 weeks.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. STAT proteins: a kaleidoscope of canonical and non-canonical functions in immunity and cancer.
   Awasthi N, Liongue C, Ward AC. · · 2021 · cited 97× · PMID 34809691 · DOI 10.1186/s13045-021-01214-y
2. The Shared Mechanism and Candidate Drugs of Multiple Sclerosis and Sjögren's Syndrome Analyzed by Bioinformatics Based on GWAS and Transcriptome Data.
   Hong X, Wang X, Rang X, Yin X, et al · · 2022 · cited 17× · PMID 35356004 · DOI 10.3389/fimmu.2022.857014
3. Role of JAK-STAT signaling pathway in pathogenesis and treatment of primary Sjögren's syndrome.
   Li M, Li M, Qiao L, Wu C, et al · · 2023 · cited 13× · PMID 37185152 · DOI 10.1097/cm9.0000000000002539
4. The Future of Targeted Treatment of Primary Sjögren's Syndrome: A Focus on Extra-Glandular Pathology.
   Zeng W, Zhou X, Yu S, Liu R, et al · · 2022 · cited 12× · PMID 36430611 · DOI 10.3390/ijms232214135
5. The role of cytokines from salivary gland epithelial cells in the immunopathology of Sjögren's syndrome.
   Dong Y, Wang T, Wu H. · · 2024 · cited 6× · PMID 39346911 · DOI 10.3389/fimmu.2024.1443455
6. Pathogenesis and Treatment of T-Large Granular Lymphocytic Leukemia (T-LGLL) in the Setting of Rheumatic Disease.
   Couette N, Jarjour W, Brammer JE, Simon Meara A. · · 2022 · cited 5× · PMID 35747794 · DOI 10.3389/fonc.2022.854499
7. Sjögren's Syndrome: Epidemiology, Classification Criteria, Molecular Pathogenesis, Diagnosis, and Treatment.
   Hu Y, Wen B, Zhang Y, Wang X, et al · · 2025 · cited 3× · PMID 40656544 · DOI 10.1002/mco2.70297