Efficacy, Safety and Immunological Evaluation of Tofacitinib in the Treatment of Primary Sjogren's Syndrome

Efficacy, Safety and Immunological Evaluation of Tofacitinib in the Treatment of Primary Sjögren's Syndrome:a Prospective Observational Study

This study aims to explore the clinical and immunological efficacy of tofacitinib on primary Sjögren's Syndrome

Study Overview

• Status: Recruiting
• Conditions: Primary Sjögren's Syndrome
• Intervention / Treatment: Drug: Tofacitinib

Detailed Description

The investigators designed a single center, open-label, prospective study. Adults with active primary Sjögren's Syndrome will be enrolled, meeting the American College of Rheumatology(ACR) & European allance of associations for rheumatology(EULAR)(2016) diagnostic criteria . Tofacitinib 5 mg bd was administered for 6 months to explore its efficacy and safety. The improvement of clinical and laboratory indexes was evaluated. Changes of immune cell subsets and cytokines were monitored.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qinghong Liu; Phone Number: +86 15774917676; Email: 166618530@qq.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Recruiting
      • Department of Rheumatology and Immunology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female >18 years of age at screening visits
2. Patients meet the American-European Consensus Group 2002 classification criteria
3. 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.

4. Dosing of antimalarials, prednisone or equivalent, cholinergic stimulants, and topical cyclosporine required to be stable for at least 4 weeks before screening and during study; maximum doses allowed:

   • Hydroxychloroquinone, 400 mg/day;
   • Prednisone, 10 mg/day

Exclusion Criteria:

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

1. Laboratory abnormality:

   • Hb≤9 g/dl
   • Neutrophil <1.0 x 109/l
   • lymphocyte<0.5 x 109/l
2. Diagnosis of other autoimmune disease, or other sicca syndrome.
3. Use rituximab or other monoclonal antibodies within 6 months.
4. Received high doses of glucocorticoid (>10 mg/d) within 1 month.
5. Serious complications: including heart failure (≥ New York Heart Association (NYHA) class III), renal insufficiency (creatinine clearance ≤ 30 ml/min), liver dysfunction (serum Alanine transaminase (ALT) or aspartate aminotransferase (AST) greater than three times the upper limit of normal, or total bilirubin greater than Normal upper limit)
6. Known allergies, hyperreactivity or intolerance of tofacitinib or its excipients.
7. Have a serious infection needing hospitalization (including but not limited to hepatitis, pneumonia, bacteremia, pyelonephritis, EB virus, tuberculosis infection), or use intravenous antibiotics to treat infection in 2 months before the enrollment.
8. Infection with HIV (HIV antibody positive serology) or hepatitis C (Hep C antibody positive serology). If seropositive, it is recommended to consult a doctor who has expertise in treating HIV or hepatitis C virus infection.
9. Any known history of malignancy in the past 5 years (except for non-melanoma skin cancer, non-melanoma skin cancer or cervical tumor without recurrence within 3 months after surgical cure prior to the first study preparation).
10. Uncontrolled mental or emotional disorders, including a history of drug and alcohol abuse over the past 3 years, may hinder the successful completion of the study.
11. Pregnant, lactating women (WCBP) are reluctant to use medically approved contraceptives during treatment and 12 months after treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: tofacitinib; Tofacitinib 5mg was taken orally twice a day for 6 months	Drug: Tofacitinib; Tofacitinib 5mg was taken orally twice a day for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological Responses	Analysis interleukin 17 (IL-17)-producing helper T (Th17) cells before and during tofacitinib treatment. P values below 0.05 are considered statistically significant in this study.	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvements in EULAR SS patient-reported index (ESSPRI), other clinical and immunological parameters	ESSPRI ranges from 0 to 10. The patient's acceptability/satisfaction of its current state (taking account of his symptoms: dryness, fatigue and pain) should be recorded. For addressing patient-reported outcomes, we define response as an improvement of ESSPRI at least one point or 15% .	week 24
Safety and tolerability of tofacitinib as assessed by incidence of adverse events reported and observed	we will report frequency of adverse events.Adverse events includes infection, tumor, abnormal neutrophil and lymphocyte count, anemia,drug-induced liver and kidney damage.	up tp 24 weeks

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 20, 2021
• Primary Completion (ANTICIPATED): January 1, 2023
• Study Completion (ANTICIPATED): October 1, 2023

Study Registration Dates

• First Submitted: October 8, 2021
• First Submitted That Met QC Criteria: October 8, 2021
• First Posted (ACTUAL): October 21, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 28, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Stomatognathic Diseases; Mouth Diseases; Lacrimal Apparatus Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Syndrome; Sjogren's Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: 20210918pss

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No