Tofacitinib for Sjogren's Syndrome

Overseen By Sasha D Clary

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

Must be taking: Antimalarials, Glucocorticoids

Must not be taking: Biologics, DMARDs, CYP3A4 inhibitors

Disqualifiers: Chronic liver disease, Renal failure, Infections, Malignant disease, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 10

Duration: 24 weeks

23 Participants Needed

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.

Will I have to stop taking my current medications?

You may need to stop certain medications before joining the trial. If you are taking methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, or other similar drugs, you must stop them at least 8 weeks before the trial. If you are on glucocorticoids or antimalarials, your dose must be stable for a certain period before the trial.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug tofacitinib for treating Sjogren's Syndrome?

Tofacitinib has been shown to reduce inflammation and improve symptoms in conditions like rheumatoid arthritis, which are also autoimmune diseases. Its ability to alleviate inflammation suggests it might help with Sjogren's Syndrome, especially since it has anti-inflammatory effects that could benefit related lung conditions. ^{1 2 3 4 5}

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. ^{2 3 5 6 7}

Is tofacitinib generally safe for humans?

Tofacitinib, also known as Xeljanz, has been studied for various conditions like rheumatoid arthritis and psoriatic arthritis. It generally has an acceptable safety profile, but some serious side effects have been observed, including infections, malignancies (cancers), and cardiovascular events, which require careful monitoring. ^{2 3 5 6 7}

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. ^{2 3 8 9 10}

How is the drug tofacitinib unique for treating Sjogren's Syndrome?

Tofacitinib is unique because it is an oral drug that works by selectively inhibiting Janus kinase (JAK) enzymes, which helps reduce inflammation and fibrosis (thickening and scarring of tissue) in conditions like Sjogren's Syndrome-associated interstitial lung disease. This mechanism is different from other treatments that may not target these specific pathways. ^{2 3 8 9 10}

Research Team

Blake M Warner, D.D.S.

Principal Investigator

National Institute of Dental and Craniofacial Research (NIDCR)

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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive tofacitinib or placebo for 168 days to evaluate safety and tolerance

24 weeks

9 visits (in-person), phone contacts between visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tofacitinib

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

National Institute of Dental and Craniofacial Research (NIDCR)

Lead Sponsor

Trials

312

Recruited

853,000+

Findings from Research

Tofacitinib significantly improved symptoms of rheumatoid arthritis (RA) in Chinese patients, with ACR20 response rates of 67.4% and 70.6% for 5 mg and 10 mg doses respectively, compared to 34.1% for placebo after 6 months.

The safety profile of tofacitinib was consistent with global data, indicating it is a safe treatment option for RA, with efficacy maintained over a 48-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis. Li, ZG., Liu, Y., Xu, HJ., et al.[2022]

Tofacitinib, a JAK1 and JAK3 inhibitor, is being tested in a 52-week trial involving 120 patients to determine its effectiveness compared to traditional therapies for treating interstitial lung disease associated with primary Sjögren's syndrome.

The primary goal of the study is to measure improvements in lung function (forced vital capacity) after treatment, while also assessing safety and other health-related quality of life indicators.

NCBI (Pubmed)

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. Gao, R., Pu, J., Wang, Y., et al.[2023]

Tofacitinib, an oral JAK inhibitor, demonstrated bioequivalence to Xeljanz® in a phase I trial involving 32 healthy Chinese subjects, with pharmacokinetic parameters such as peak concentration and area under the curve falling within the acceptable range of 80-125%.

The safety profile of tofacitinib was found to be comparable to that of Xeljanz®, supporting its potential for clinical use in treating inflammatory and autoimmune diseases.

NCBI (Pubmed)

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. Xu, Z., Wang, Y., Liu, Z., et al.[2022]

Tofacitinib is an effective treatment for moderate to severe rheumatoid arthritis (RA), showing significant improvements in symptoms and quality of life in clinical studies lasting up to 96 months, whether used alone or in combination with other DMARDs.

The medication is generally well tolerated, with most side effects being mild to moderate, although there is a higher incidence of herpes zoster compared to the general RA population, indicating that while manageable, monitoring for infections is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Rheumatoid Arthritis. Dhillon, S.[2022]

Tofacitinib (Xeljanz®) is an effective oral treatment for rheumatoid arthritis (RA), showing significant improvements in symptoms and quality of life compared to placebo, as demonstrated in Phase III clinical trials.

While tofacitinib has a generally acceptable safety profile, it can lead to serious adverse effects such as infections and cardiovascular events, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European perspective on the management of rheumatoid arthritis: clinical utility of tofacitinib. Kawalec, P., Śladowska, K., Malinowska-Lipień, I., et al.[2020]

Tofacitinib (Xeljanz) is an effective treatment for rheumatoid arthritis (RA), showing comparable efficacy to adalimumab and improving disease control when used alone or with methotrexate.

While tofacitinib can reduce structural damage in RA, it carries risks of side effects such as upper respiratory infections and tuberculosis, necessitating careful monitoring of blood counts, lipids, and organ function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A new therapeutical option for chronic inflammation in rheumatology: janus kinases inhibitors (JAK)]. Varisco, PA., So, A.[2014]

Tofacitinib (5 mg twice daily) significantly improves key symptoms of active psoriatic arthritis (PsA) and related conditions after 3 months of treatment, with benefits maintained for up to 30 months in ongoing studies.

The drug has an acceptable safety profile, showing low rates of serious infections, malignancies, and other adverse events over 36 months, indicating it is a viable option for patients who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib: A Review in Psoriatic Arthritis. Paik, J., Deeks, ED.[2020]

In a phase 3 study involving 611 patients, tofacitinib significantly improved symptoms of rheumatoid arthritis, with 59.8% and 65.7% of patients achieving at least a 20% improvement in the ACR scale at 5 mg and 10 mg doses, respectively, compared to only 26.7% in the placebo group.

Tofacitinib treatment led to greater improvements in physical function as measured by the HAQ-DI scores, but it did not significantly increase the percentage of patients achieving low disease activity (DAS28-4[ESR] < 2.6) compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. Fleischmann, R., Kremer, J., Cush, J., et al.[2022]

In a 12-month phase 3 trial with 717 rheumatoid arthritis patients, tofacitinib (5 mg and 10 mg doses) showed significantly higher efficacy compared to placebo, with ACR 20 response rates of 51.5% and 52.6%, respectively, indicating effective improvement in symptoms.

Tofacitinib was found to have a higher incidence of adverse events compared to placebo, including cases of pulmonary tuberculosis and changes in cholesterol and neutrophil levels, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. van Vollenhoven, RF., Fleischmann, R., Cohen, S., et al.[2022]

Tofacitinib, an oral medication for rheumatoid arthritis, allows patients to maintain remission or low disease activity even after discontinuing methotrexate or glucocorticoids, with 70.4% and 72.7% of patients respectively achieving these outcomes by year 3.

Patients who had an incomplete response to tofacitinib may benefit from adding methotrexate, as those who initiated it after showing inadequate response experienced significant improvements in their RA symptoms.

NCBI (Pubmed)

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. Fleischmann, R., Wollenhaupt, J., Cohen, S., et al.[2020]

References

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

Efficacy and Safety of Tofacitinib in Chinese Patients with Rheumatoid Arthritis. [2022]

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]

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]

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

Tofacitinib: A Review in Rheumatoid Arthritis. [2022]

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

European perspective on the management of rheumatoid arthritis: clinical utility of tofacitinib. [2020]

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

[A new therapeutical option for chronic inflammation in rheumatology: janus kinases inhibitors (JAK)]. [2014]

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

Tofacitinib: A Review in Psoriatic Arthritis. [2020]

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

Placebo-controlled trial of tofacitinib monotherapy in rheumatoid arthritis. [2022]

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

Tofacitinib or adalimumab versus placebo in rheumatoid arthritis. [2022]

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]