Clinical trial: Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren's Syndrome (NCT04496960)

Eligibility criteria:
-  INCLUSION CRITERIA:

        In order to be eligible to participate in this study, an individual must meet all of the
        following criteria:

          1. Ability of participant to understand and the willingness to sign a written informed
             consentdocument.

          2. Participation and enrollment in companion protocol, 15-D-0051, Characterization of
             Diseases with Salivary Gland Involvement

          3. Stated willingness to comply with all study procedures and availability for the
             duration of the study

          4. Male or female, aged between 18-75 years

          5. In good general health as evidenced by medical history

          6. Meets the 2002 American European Consensus Group classification criteria for primary
             Sjogren's Syndrome with mild to moderate disease activity defined as ESSDAI between 2
             to 13 at the screening visit and >0 ml/min/gland stimulated saliva flow.

          7. Ability to take oral medication and be willing to adhere to the study intervention
             regimen

          8. If on glucocorticoids, the dose must be less than 10 mg daily and stable for the 4
             weeks (28 days) prior to screening visit.

          9. 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.

         10. 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.

         11. 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.

         12. Agreement to adhere to Lifestyle Considerations throughout study duration

        EXCLUSION CRITERIA:

        In order to be eligible to participate in this study, an individual must not meet any of
        the following criteria:

          1. Current or prior treatment with rituximab, belimumab or any other biologic agent in
             the 6 months prior to screening.

          2. Current treatment with methotrexate, azathioprine, mycophenolate mofetil,
             cyclosporine, tacrolimus). Participants previously on methotrexate, azathioprine,
             mycophenolate mofetil, cyclosporine or tacrolimus should have withdrawn drug for at
             least 8 weeks (56 days) at the time of screening.

          3. Treatment with cyclophosphamide, pulse methylprednisolone or IVIG within 6 months
             prior to screening.

          4. 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.

          5. Focus Score <= 1.0 at their last salivary gland biopsy

          6. History of chronic liver disease or elevated LFTs:

          7. ALT or AST >= 2x upper limit of normal at screening

          8. Serum unconjugated bilirubin > 2mg/dL at screening

          9. Serum creatinine >1.5mg/dL.

         10. Protein to creatinine ratio of more than 1mg/dL repeated and confirmed three times or
             confirmed with 24 hours urine protein of more than 1000 mg).

         11. Active urinary sediment (WBC, RBC or mixed cellular casts 1+ or more /hpf).

         12. 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.

         13. WBC <2500/microliter or ANC <1,000/microliter, Hgb <9.0 g/dL or platelets
             <70,000/microliter or absolute lymphocyte count < 500/microliter.

         14. Pregnant or lactating women. Women of childbearing potential are required to have a
             negative pregnancy test at screening.

         15. A history of drug or alcohol abuse within the 6 months prior to screening.

         16. Currently receiving hemodialysis, peritoneal dialysis, or intestinal dialysis.

         17. Active infection that requires the use of oral or intravenous antibiotics unresolved
             at least

        14 days prior to the administration of the first dose of study medication.

        18. Active chronic infections including but not limited to HIV, Hepatitis B, Hepatitis C,
        and BK viremia at screening visit.

        19. Current or previous diagnosis of malignant disease, except for basal cell or squamous
        cell carcinoma of the skin with complete excision and clear borders or adequately treated
        in situ carcinoma of the cervix.

        20. Known active tuberculosis. Participants with untreated latent tuberculosis (LTB) will
        not be excluded but will be evaluated by an infectious disease (I.D.) consultant and may
        become eligible for trial based on infectious disease consultant recommendations.

        21. History of opportunistic infections.

        22. Participants with active renal or central nervous system disease or a high activity
        level in any organ system (except articular) in ESSDAI .

        23. Significant impairment of major organ function (lung, heart, liver, kidney) or any
        condition that, in the opinion of the Investigator, would jeopardize the participant s
        safety following exposure to the study drug.

        24. Known history of arterial or venous thrombosis or at high risk for clotting disorder

        25. Psychiatric illness or history of medical non-compliance that the study team feels will
        make the patient unlikely to complete the study

        26. Uncontrolled thyroid disease as per PI or medically responsible investigator.

        27. Known allergic reactions to Tofacitinib or its components

        28. Treatment with another investigational drug/intervention within six months.

        29. Current smoker or tobacco use within 3 months.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 75 Years

Patient description (medical language): A 40-year-old woman comes to the clinic complaining of gritty sensation in her eyes. She also has difficulty swallowing dry foods with no pain or heartburn.  The patient is a schoolteacher and must drink water frequently during lectures due to her mouth dryness.  She also reports occasional joint pain.  Medical history is not significant other than the confirmed Sjogren disease with no other rheumatologic disease.  She is sexually active with her husband and has 2 children both delivered by natural vaginal delivery. She has no history of any kind of surgery. Physical examination shows conjunctival erythema and cracking of the lips. The remainder of the examination and history is normal. Her lab result shows elevated ESR (50 mm/h)

Patient description (patient's own words): I went to the clinic because I had a terrible gritty sensation in my eyes. It was also hard to swallow dry food, but it didn't burn, and there was no pain. I'm a 40-year-old female school teacher and I should drink water for the lectures because otherwise, my mouth gets really dry. I also have joint pain from time to time. I have been diagnosed with Sjogren disease but no other rheumatologic disease. I have a husband, we're sexually active, and I also have two lovely children that I delivered both naturally. I never undergone any surgery. Physical examination when I came to the clinic, and it showed cracking on my lips and a pink eye. The rest was fine. I also did some lab tests, and they came back with high ESR.

Does the patient match the trial criteria? 1