Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren Disease

NCT07281456 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10002290002290-D
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Sjogren disease is an autoimmune disease - that is, a disease that causes the body's immune system to attack its own organs and tissues. Sjogren disease can affect the kidneys, lungs, or other organs. It can also cause dry mouth and eyes, fever, joint pain, rashes, and other symptoms. Researchers want to know if a drug approved to treat rheumatoid arthritis and other autoimmune diseases can help people with Sjogren disease. Objective: To test a drug (tofacitinib) in people with Sjogren disease. Eligibility: People aged 18 to 75 years with Sjogren disease. They must be enrolled in protocol 15-D-0051. Design:

• Participants will be screened. They will have a physical exam with blood and urine tests. They will give samples of saliva; a small sample of tissue will be taken from a salivary gland. They will have a test of their heart function. They will have an eye exam, including a test for dry eyes.
• Tofacitinib is a tablet taken by mouth. Participants will take the drug twice a day at home.
• Participants will have 9 clinic visits over 28 weeks. Each visit will take up to 5 hours. In addition to repeated tests, they will have tests of the speed and pressure of blood flow through their body. They will complete health questionnaires throughout the study.
• Participants will also have 5 phone visits during the study. They will review their health and study treatments.
• They will have 1 final visit after they stop taking the drug.

Conditions

Sjogren's Syndrome

Keywords

Salivary; Dry Mouth; Safety; Inflammation; Xerostomia; Jak; Autoimmune; Xerophthalmia; Lacrimal; Exocrine

Outcome Measures

Primary Outcomes (2)

• Number of Adverse Events by Grade/Category

  Count of adverse events by grade was assessed using the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to adverse event. Serious is defined as any grade 3 or higher adverse event. Toxicity is defined as any study drug-related Grade 3 or higher adverse event.

  Up to Day 196

• Participants With Adverse Events

  Number participants with any adverse events by grade and severity was assessed using the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activity of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event. Serious is defined as any grade 3 or higher adverse event. Toxicity is defined as any study drug-related Grade 3 or higher adverse event.

  Up to Day 196

Secondary Outcomes (5)

• Change in Physicians Global Assessment (PGA) Score

  Day 168 minus Day 1

• Change in EULAR Sjogren's Syndrome (SS) Disease Activity Index (ESSDAI) Score

  Day 168 minus Day 1

• Change in Whole Unstimulated Saliva Flow

  Day 168 minus Day 1

• Change in Whole Stimulated Saliva Flow

  Day 168 minus Day 1

• Change in EULAR Sjogren's Syndrome (SS) Patient Reported Index (ESSPRI)

  Day 168 minus Day 1

Study Arms (1)

Drug: Tofacitinib

EXPERIMENTAL

Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.

Drug: Tofacitinib

Interventions

Tofacitinib DRUG

XELJANZ(R) is the citrate salt of tofacitinib. Tofacitinib citrate is a white to off-white powder. XELJANZ(R) is supplied for oral administration as 5 mg tofacitinib (equivalent to 8 mg tofacitinib citrate) white round, immediate-release film-coated tablet.

Drug: Tofacitinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Additionally, 20-D-0131(Safety of Tofacitinib, an oral Janus Kinase Inhibitor, in primary Sjogren's syndrome Phase Ib-IIa placebo-controlled clinical trial and associated mechanistic studies) participants who, at unblinding, received a placebo will be contacted and asked to return to the study to participate in this study.
• To be eligible to participate in this study, an individual must meet all of the following criteria:
• Ability of participant to understand and the willingness to sign a written informed consent document.
• Participation and enrollment in companion protocol, 15-D-0051, Characterization of Diseases with Salivary Gland Involvement.
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged between 18-75 years old
• In good general health as evidenced by medical history
• Meets the 2002 American European Consensus Group classification criteria for Sjogren's disease or 2016 American College of Rheumatology/European League against Rheumatism Classification Criteria (ACR-EULAR) with mild to moderate disease activity defined as ESSDAI between 0 and 13 at the screening visit and \>0 ml/min/gland stimulated saliva flow.
• Ability to take oral medication and be willing to adhere to the study intervention regimen
• If on glucocorticoids, the dose must be less than 10 mg daily and stable for the 4 weeks (28 days) prior to the screening visit.
• If on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, the dose must have been stable for the 12 weeks (96 days) prior to screening visit. The maximum allowed dose is hydroxychloroquine up to 400 mg/day or 6.5 mg/kg/day if more than 400 mg/day. The maximum allowed dose for chloroquine phosphate is up to 500 mg daily and for quinacrine up to 100 mg daily.
• Participants may be on lipid lowering medications if initiated at least 3 months prior to the screening visit and dose must be stable for 4 weeks (28 days) prior to study entry.
• Males and females with potential for reproduction must agree to practice effective birth control measures. Females should be on adequate contraception if they are of child-bearing potential documented by a clinician, unless participants or spouse have previously undergone a sterilization procedure. Adequate birth control measures are: intrauterine device (IUD) alone or hormone implants, hormone patches, injectable, or oral contraceptives plus a barrier method (male condom, female condom or diaphragm), abstinence or a vasectomized partner.
• Agreement to adhere to Lifestyle Considerations throughout study duration

You may not qualify if:

• To be eligible to participate in this study, an individual must not meet any of the following criteria:
• Current or prior treatment with rituximab, belimumab, or any other biologic agent in the 6 months prior to screening.
• Current or prior treatment with Tofacitinib for more than 6 months in the last 2 years prior to screening.
• Current treatment with methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, or other less common immunomodulatory drugs such as those falling into the class of disease-modifying antirheumatic drugs (DMARDs), not otherwise specified herein. Participants previously on methotrexate, azathioprine, mycophenolate mofetil, cyclosporine or tacrolimus, or other DMARDs should have withdrawn drug for at least 8 weeks (56 days) at the time of screening. The use of topical or ophthalmic preparations of cyclosporine, tacrolimus, or other DMARDs is permitted and does not require an 8-week withdrawal period.
• Treatment with cyclophosphamide, pulse methylprednisolone or IVIG within 6 months prior to screening.
• Current treatment with potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., ketoconazole) or receiving one or more concomitant medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole) that would increase serum availability of Tofacitinib. Past treatment with the agent is allowed if it was more than a week prior to the administration of the first dose of study medication.
• History of chronic liver disease, not including well-controlled Sjogren's-related chronic liver disease or elevated LFTs:
• ALT or AST \>= 2x upper limit of normal at screening
• Serum unconjugated bilirubin \> 2mg/dL at screening
• Serum creatinine \>1.5mg/dL.
• Protein to creatinine ratio of more than 1mg/dL at screening (repeated and confirmed three times or confirmed with 24 hours urine protein of more than 1000mg).
• Active urinary sediment (WBC, RBC or mixed cellular casts 1+ or more /hpf).
• Hypercholesterolemia: Values after 8-12 hour fasting blood specimen: total cholesterol \>250 mg/dL or LDL \>180 mg/dL or hypertriglyceridemia (triglyceride \>300 mg/dL) within - 45 days of screening visit.
• WBC \<2500/microL or ANC \<1,000/microL, Hgb \<9.0 g/dL or platelets \<70,000/microL or absolute lymphocyte count \< 500/microL.
• Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test at screening.

Sponsors & Collaborators

• National Institute of Dental and Craniofacial Research (NIDCR): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sjogren's Syndrome; Xerostomia; Inflammation; Xerophthalmia

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Conjunctival Diseases

Study Officials

• Blake M Warner, D.D.S.

  National Institute of Dental and Craniofacial Research (NIDCR)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sasha D Nuby

CONTACT

(301) 529-7924; sasha.clary@nih.gov

Blake M Warner, D.D.S.

CONTACT

(301) 500-8063; blake.warner@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: December 15, 2025
• Study Start: December 18, 2025
• Primary Completion (Estimated): December 15, 2030
• Study Completion (Estimated): December 15, 2030
• Last Updated: March 30, 2026

Record last verified: 2026-03-24

Data Sharing

• IPD Sharing: Will share
• Time Frame: At the time of publication or after 3 years, whichever comes first.
• Access Criteria: This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed journals. Data from this study may be requested from other researchers 3 years after the completion of the primary endpoint.

Locations

US (1)