Clinical trial NCT06862284: Therapeutic Effect of Upadacitinib in Primary Sjögren's Syndrome
Official title: Efficacy, Safety and Immunological Effect of Upadacitinib in the Treatment of Primary Sjögren's Syndrome
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Primary Sjögren's Syndrome (pSS)
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2025-03-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to explore the efficacy and safety of upadacitinib and clarify the influence on immune function in the treatment of primary Sjögren's Syndrome.

Detailed description: This is an open-label, single-center, randomized controlled trial of upadacitinib in the treatment of active primary Sjögren's Syndrome. The enrollment was based on the American College of Rheumatology(ACR) and European League Against Rheumatism (EULAR)(2016) diagnostic criteria. The efficacy and safety were evaluated in participants given upadacitinib 15mg/day and a proper, stable dose of hydroxychloroquine 400mg/day. Changes in clinical manifestation, laboratory indexes, and immunological indicators were explored in the process.

Eligibility criteria: Inclusion Criteria:

1. Male or female \>18 years of age at screening visits
2. Participants with diagnosis of pSS according to the 2016 ACR/EULAR criteria
3. Participants have an ESSDAI score ≥ 5
4. Participants must be on a stable dose of prednisone (≤10mg/day), antimalarials or equivalent, and cholinergic stimulants prior to Baseline.
5. Participants previously on other immunosuppressive drugs (methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, iguratimod) should have withdrawn drug for at least 8 weeks (56 days) at the time of screening
6. If the subject has evidence of new latent tuberculosis (TB) infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis before continuing to receive the study drug.
7. If female, the subject must be postmenopausal, OR permanently surgically sterile, OR for women of childbearing potential practicing at least one protocol-specified method of birth control, that is effective from Study Day 1 through at least 30 days after the last dose of study drug.
8. The patient must be informed in writing of the consent to participate in the trial and the patient is expected to be able to comply with the requirements of the study follow-up plan and other protocols.

Exclusion Criteria:

Any subject meeting any of the following criteria should be excluded:

1. Pregnant or breastfeeding female.
2. Diagnosis of other autoimmune disease, or other sicca syndrome.
3. Laboratory value abnormality:

(1)Serum aspartate transaminase (AST) or alanine transaminase (ALT) \> 3.0 × upper limit of normal (ULN); (2)Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula \< 40 mL/min/1.73m\^2; (3)Total white blood cell count (WBC) \< 2,000/μL; (4)Absolute neutrophil count (ANC) \< 1,000/μL; (5)Platelet count \< 50,000/μL; (6)Absolute lymphocytes count \< 500/μL; (7)Hemoglobin \< 8 g/dL.

4. Ongoing infections at Week 0 that have not been successfully treated.

5. Infection with HIV ( HIV antibody positive serological test ) or hepatitis C ( hepatitis C antibody positive serological test ). If the serum reaction is positive, it is recommended to consult a doctor with expertise in the treatment of HIV or hepatitis C virus infection.

6. History of any known malignancy in the last 5 years (except non-melanoma skin cancer, non-melanoma skin cancer or cervical tumors that have not recurred within 3 months after surgical cure prior to screening).

7. Underlying cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal, hematological or neurological conditions, chronic or latent infectious diseases, or immune deficiency which places the patient at an unacceptable risk for participation in the study.

8. Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tocilizumab, sirukumab, sarilumab, upadacitinib, tofacitinib, baricitinib, ruxolitinib, peficitinib, and filgotinib).

9. Exposure to biological DMARDs in two months before screening.

10. Enrollment in another interventional clinical study while participating in this study.

11. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive the study drug.

Primary outcomes:
measure: Treatent response assessed by the Sjögren's Tool for Assessing Response (STAR)
timeFrame: week 24
Secondary outcomes:
measure: Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score during treatment
timeFrame: week 4, 12, 24, 52
measure: Change From Baseline in EULAR SS patient-reported index (ESSPRI) during treatment
timeFrame: week 4, 12, 24, 52
measure: Variation of lymphocyte subpopulations during the treatment of upadacitinib
timeFrame: week 4, 12, 24, 52
measure: Alteration of inflammatory biomarkers and pathways after treatment of upadacitinib
timeFrame: week 4, 12, 24, 52
measure: Change in quality of life(QOL) measured by 5-level EQ-5D version (EQ-5D-5L) compared with baseline
timeFrame: week 4, 12, 24, 52
Other outcomes:
Locations:
city: Beijing
country: China
facility: Department of Rheumatology and Immunology, Peking University People's Hospital
Study officials:
affiliation: Peking University Institute of Rheuamotology and Immunology
name: Jing He
role: PRINCIPAL_INVESTIGATOR
References: