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

Overview

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.

Interventions

• Drug Upadacitinib (ABT-494)
  Upadacitinib 15mg Qd for 52 weeks
• Drug Hydroxychloroquine (HCQ)
  Hydroxychloroquine 200mg Bid for 52 weeks

Primary outcome measures

• Treatent response assessed by the Sjögren's Tool for Assessing Response (STAR) [Time frame: week 24]

Secondary outcome measures (5)

• Change From Baseline in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Total Score during treatment [Time frame: week 4, 12, 24, 52]
• Change From Baseline in EULAR SS patient-reported index (ESSPRI) during treatment [Time frame: week 4, 12, 24, 52]
• Variation of lymphocyte subpopulations during the treatment of upadacitinib [Time frame: week 4, 12, 24, 52]
• Alteration of inflammatory biomarkers and pathways after treatment of upadacitinib [Time frame: week 4, 12, 24, 52]
• Change in quality of life(QOL) measured by 5-level EQ-5D version (EQ-5D-5L) compared with baseline [Time frame: week 4, 12, 24, 52]

Eligibility criteria

Inclusion criteria

• Male or female >18 years of age at screening visits
• Participants with diagnosis of pSS according to the 2016 ACR/EULAR criteria
• Participants have an ESSDAI score ≥ 5
• Participants must be on a stable dose of prednisone (≤10mg/day), antimalarials or equivalent, and cholinergic stimulants prior to Baseline.
• 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drugs (methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, iguratimod) should have withdrawn drug for at least 8 weeks (56 days) at the time of screening
• 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.
• 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.
• 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:

• Pregnant or breastfeeding female.
• Diagnosis of other autoimmune disease, or other sicca syndrome.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Rheumatology and Immunology, Peking University People's Hospital — Beijing

Identifiers

NCT: NCT06862284 · pss2024upa

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗