Tofacitinib for Sjogren's Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by Blake M Warner, D.D.S.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial protocol specifies that you must stop certain medications before joining. If you are currently taking methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, or other DMARDs, you need to stop them at least 8 weeks before screening. If you are on glucocorticoids, the dose must be less than 10 mg daily and stable for 4 weeks before screening. If you are on hydroxychloroquine or other antimalarials, the dose must be stable for 12 weeks before screening. You can continue lipid-lowering medications if they were started at least 3 months before screening and the dose is stable for 4 weeks before study entry.

What data supports the idea that Tofacitinib for Sjogren's Syndrome is an effective treatment?

The available research shows that Tofacitinib may help with lung problems related to Sjogren's Syndrome due to its ability to reduce inflammation and prevent tissue damage. However, most of the data focuses on its use for rheumatoid arthritis, where it has been shown to reduce symptoms and improve quality of life. This suggests it might be effective for similar inflammatory conditions, but more specific studies on Sjogren's Syndrome are needed to confirm its effectiveness.

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What safety data is available for Tofacitinib?

Tofacitinib, also known as Xeljanz, is a Janus kinase (JAK) inhibitor used for treating various inflammatory and autoimmune diseases, including rheumatoid arthritis and psoriatic arthritis. Safety data from clinical trials indicate that Tofacitinib has an acceptable safety profile, but some severe adverse effects have been observed. These include serious infections, opportunistic infections (such as tuberculosis and herpes zoster), malignancies, and cardiovascular events, which require strict monitoring. Common side effects include upper respiratory tract infections. Laboratory parameters generally remain stable over long-term treatment. Tofacitinib offers a convenient oral administration alternative to subcutaneous or intravenous biologic drugs.

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Is the drug Tofacitinib a promising treatment for Sjogren's Syndrome?

Tofacitinib shows promise as a treatment for Sjogren's Syndrome because it has anti-inflammatory and antifibrotic effects that may help improve lung conditions associated with the disease.

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Eligibility Criteria

Adults aged 18-75 with Primary Sjogren's Syndrome (SS) who have mild-to-moderate disease activity. Participants can be new to treatment or may have tried some immunosuppressive therapies, but not certain strong medications. They must be in good health overall and agree to use effective birth control if applicable.

Inclusion Criteria

I can take pills and will follow the study's treatment plan.

I have Sjögren's syndrome with mild to moderate symptoms.

Ability of participant to understand and the willingness to sign a written informed consent document

Exclusion Criteria

You are allergic to Tofacitinib or any of its ingredients.

I have had infections due to a weakened immune system.

I haven't taken rituximab, belimumab, or similar drugs in the last 6 months.

Participant Groups

The trial is testing the safety and tolerance of Tofacitinib, an oral medication, compared to a placebo over a period of 168 days. It includes various tests like heart exams, eye exams, saliva collection, blood pressure monitoring, and questionnaires about health during nine study visits over 28 weeks.

Group I: Subjects with SS Experimental Treatment 1 Intervention

Receiving tofacidinib

Group II: Placebo group Placebo Group 1 Intervention

Receiving placebo

Tofacitinib is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Xeljanz for:

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Ankylosing Spondylitis
• Polyarticular Course Juvenile Idiopathic Arthritis

🇪🇺 Approved in European Union as Xeljanz for:

• Rheumatoid Arthritis
• Psoriatic Arthritis
• Ulcerative Colitis
• Ankylosing Spondylitis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Institute of Dental and Craniofacial Research (NIDCR) Lead Sponsor

References

1. China pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis. [2022] Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies.

2. England pubmed.ncbi.nlm.nih.gov

Tofacitinib in the treatment of primary Sjögren's syndrome-associated interstitial lung disease: study protocol for a prospective, randomized, controlled and open-label trial. [2023] Tofacitinib, a selective inhibitor of JAK1 and/or JAK3, is considered to alleviate the pulmonary condition of primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD) through its anti-inflammatory and antifibrotic effects.

3. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized, crossover, phase I clinical study to evaluate bioequivalence and safety of tofacitinib and Xeljanz® in Chinese healthy subjects. [2022] Tofacitinib is an oral Janus kinase (JAK) inhibitor that has been marketed and approved in the USA for the clinical treatment of rheumatoid arthritis, psoriasis and other inflammatory and autoimmune diseases. A phase I clinical trial was conducted to compare the bioequivalence and safety of tofacitinib (Chia Tai Tianqing Pharmaceutical Group Co., Ltd.) and Xeljanz® (Pfizer Inc.) in healthy Chinese subjects, providing basis for the clinical application of tofacitinib.

4. New Zealand pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Rheumatoid Arthritis. [2022] Tofacitinib (Xeljanz®) is a potent, selective JAK inhibitor that preferentially inhibits Janus kinase (JAK) 1 and JAK3. In the EU, oral tofacitinib 5 mg twice daily is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant of, one or more DMARDs. Several clinical studies of ≤ 24 months' duration showed that tofacitinib monotherapy (as first- or second-line treatment) and combination therapy with a conventional synthetic DMARD (csDMARD; as second- or third-line treatment) was effective in reducing signs and symptoms of disease and improving health-related quality of life (HR-QOL), with benefits sustained during long-term therapy (≤ 96 months). Tofacitinib monotherapy inhibited progression of structural damage in methotrexate-naïve patients during ≤ 24 months' treatment, with beneficial effects also seen in patients receiving tofacitinib plus methotrexate as second-line therapy for 12 months. Tofacitinib was generally well tolerated during ≤ 114 months' treatment, with most adverse events of mild or moderate severity. The tolerability profile of tofacitinib was generally similar to that of biological DMARDs (bDMARDs), with infections and infestations the most common adverse events (AEs) in tofacitinib recipients. However, the incidence of herpes zoster (HZ) was higher with tofacitinib than in the general RA population, although infections were clinically manageable. When added to background methotrexate, tofacitinib was noninferior to adalimumab in terms of efficacy, and both combination therapies had generally similar tolerability profiles. Although additional comparative studies are needed to more definitively position tofacitinib relative to bDMARDs and other targeted synthetic DMARDs, current evidence indicates that oral tofacitinib is a useful option for the treatment of patients with RA.

5. New Zealand pubmed.ncbi.nlm.nih.gov

European perspective on the management of rheumatoid arthritis: clinical utility of tofacitinib. [2020] Xeljanz® (tofacitinib) is an oral small-molecule inhibitor that reversibly inhibits Janus-activated kinase (JAK)-dependent cytokine signaling, thus reducing inflammation. As a result of these mechanisms, effects on the immune system such as a moderate decrease in the total lymphocyte count, a dose-dependent decrease in natural killer (NK) cell count, and an increase in B-cell count have been observed. Therefore, tofacitinib provides an innovative approach to modulating the immune and inflammatory responses in patients with rheumatoid arthritis (RA), which is especially important in individuals who do not respond to tumor necrosis factor inhibitors or show a loss of response over time. The aim of this article was to review studies on the pharmacology, mode of action, pharmacokinetics, efficacy, and safety of tofacitinib in patients with RA. Tofacitinib has been shown to reduce symptoms of RA and improve the quality of life in the analyzed groups of patients. Moreover, it showed high efficacy and an acceptable safety profile in Phase III randomized clinical trials on RA and was the first JAK inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in the RA therapy, thus providing a useful alternative treatment strategy. Randomized controlled studies revealed a significant benefit over placebo in efficacy outcomes (American College of Rheumatology [ACR] 20 and ACR50 response rates); accordingly, clinically meaningful improvements in patient-related outcomes compared with placebo have been reported. The safety profile seems acceptable, although some severe adverse effects have been observed, including serious infections, opportunistic infections (including tuberculosis and herpes zoster), malignancies, and cardiovascular events, which require strict monitoring irrespective of the duration of tofacitinib administration. As an oral drug, tofacitinib offers an alternative to subcutaneous or intravenous biologic drugs and should be recognized as a more convenient way of drug administration.

6. Switzerland pubmed.ncbi.nlm.nih.gov

[A new therapeutical option for chronic inflammation in rheumatology: janus kinases inhibitors (JAK)]. [2014] In the last 15 years, the therapeutical options for the treatment of chronic inflammatory diseases in rheumatology have increased a lot. Nevertheless, some patients do not respond or respond partially to the current therapies--including to the biologics therapy. Tofacitinib (Xeljanz) is now on the Swiss market. It inhibits the JAK pathway. Tofacitinib--as monotherapy or with methotrexate--improves the control of rheumatoid arthritis (RA). In a comparative study, tofacitinib was as effective as adalimumab. Further, tofacitinib reduced structural damages in RA and is considered as an alternative, in case of non-response, to anti-TNF and probably to other biologics therapy. The side effects are upper respiratory tract and opportunist infections and tuberculosis. Blood count, lipids, kidney function, liver tests, CK and blood pressure have to be monitored.

7. New Zealand pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Psoriatic Arthritis. [2020] Tofacitinib (Xeljanz®) is the first Janus kinase (JAK) inhibitor approved at a dosage of 5 mg twice daily (BID) in the EU and the USA for the treatment of active psoriatic arthritis (PsA), where it is indicated in combination with methotrexate for patients who have had an inadequate response or who have been intolerant to a prior therapy with a disease-modifying antirheumatic drug (DMARD). Two well-designed phase III trials (OPAL Broaden and OPAL Beyond) in patients with PsA with or without prior tumour necrosis factor inhibitor (TNFi) therapy showed that tofacitinib 5 mg BID (co-administered with methotrexate or another approved conventional synthetic DMARD) significantly improved the key clinical signs/symptoms and disability associated with PsA after 3 months of treatment, while also improving skin psoriasis, enthesitis, dactylitis, physical function and fatigue. According to interim data, the improvements in clinical signs/symptoms were maintained for up to 30 months in the ongoing long-term extension study OPAL Balance, with minimal radiographic progression seen after 12 months' therapy in the OPAL Broaden study. Tofacitinib 5 mg BID had an acceptable tolerability profile, with low incidences of serious infections, malignancies, cardiovascular events and gastrointestinal perforations over 36 months. Changes in laboratory parameters generally remained stable over 36 months of treatment. Although further studies are required to more definitively establish its efficacy and safety, currently available evidence indicates that tofacitinib expands the treatment options available for the treatment of PsA in patients who have had an inadequate response or who have been intolerant to a prior DMARD therapy.

8. United States pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. [2022] Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis.

9. United States pubmed.ncbi.nlm.nih.gov

Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. [2022] Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis.

10. England pubmed.ncbi.nlm.nih.gov

Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis. [2020] Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy.