Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren's Syndrome

NCT04496960 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 20013120-D-0131
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Background: An autoimmune disease is one in which the immune system attacks a person's own body. Sjogren's syndrome (SS) is an autoimmune disease. It often involves multiple systems and organs of the body. Researchers are trying to find new, more effective and safe treatments for SS. Objective: To evaluate the safety and tolerance of tofacitinib in people with SS. Eligibility: Adults ages 18-75 with SS. Design: Participants will be screened on a separate protocol. They will undergo:

• Medical and dental history
• Physical exam
• Medicine review
• Electrocardiogram to test the heart s electrical activity (Participants will lay on a table. Sticky pads will be placed on their body.)
• Eye exam and test for dry eyes
• Oral, head, and neck exams
• Plaque collection (Dental plaques and tongue and mucosal scrapings will be collected using a small tongue depressor.)
• Salivary gland ultrasound
• Blood and urine tests
• Minor salivary gland biopsy (The lower lip will be numbed. Several tiny salivary glands will be removed through a small incision.)
• Saliva collection
• Disease assessment. Participants will repeat some of the screening tests during the study. Participants will take capsules of the study drug or a placebo by mouth for 168 days. Participants will have tests to measure blood pressure and the speed of blood flow through the organs. They will also have a test that examines the function and reaction of the blood vessels. For these tests, they will wear blood pressure cuffs and other sensors. Participants will complete questionnaires about their health. Participants will have 9 study visits over 28 weeks. They may be contacted by phone between study visits.

Conditions

Sjogren's Syndrome

Keywords

Salivary; Dry Mouth; Safety; Inflammation; Xerostomia

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 Sjögren'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 Sjögren's Syndrome (SS) Patient Reported Index (ESSPRI)

  Day 168 minus day 1

Study Arms (2)

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

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Placebo OTHER

white, round, film-coated tablet

Placebo

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.

Also known as: Xeljanz

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:

• In order 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
• In good general health as evidenced by medical history
• Meets the 2002 American European Consensus Group classification criteria for primary Sjogren's Syndrome 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 to 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 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:

• In order 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 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.
• 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 aforementioned 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 liver function tests (LFT):
• Alanine aminotransferase (ALT) or aspartate aminotransferase (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, red blood cell (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/microliter or absolute neutrophil count (ANC) \<1,000/microliter, Hgb \<9.0 g/dL or platelets \<70,000/microliter or absolute lymphocyte count \< 500/microliter.
• Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test at screening.
• A history of drug or alcohol abuse within the 6 months prior to 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

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sjogren's Syndrome; Xerostomia; Inflammation

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

Results Point of Contact

• Title: Dr. Blake Warner
• Organization: National Institute of Dental and Craniofacial Research

blake.warner@nih.gov

+1 301 500 8063

Study Officials

• Blake M Warner, D.D.S.

  National Institute of Dental and Craniofacial Research (NIDCR)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2020
• First Posted: August 4, 2020
• Study Start: May 18, 2021
• Primary Completion: January 14, 2025
• Study Completion (Estimated): September 22, 2026
• Last Updated: December 18, 2025
• Results First Posted: December 18, 2025

Record last verified: 2025-12-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: At the time of publication or after 3 years, which ever comes first.
• Access Criteria: NIH's policy for data-sharing for federally funded genome-wide association studies requires that genotypic and phenotypic information from such studies will be made available through the NIH data repository. Only coded de-identified data will be available.

Locations

US (1)