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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tofacitinib, a Janus kinase inhibitor, to determine its safety and tolerability for people with Sjogren's syndrome. This autoimmune disease causes the immune system to attack the body, leading to symptoms like dry eyes and mouth. Participants will receive either the drug or a placebo to compare results. Those diagnosed with mild to moderate Sjogren's syndrome who can take oral medication might be suitable for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that tofacitinib is likely to be safe for humans?

Research has shown that tofacitinib is generally safe for humans. In studies involving patients with various conditions, most side effects were mild, though some patients experienced serious side effects. For instance, in one study with 225 patients, 89.3% reported side effects, and 15.1% experienced serious ones. This indicates that while many tolerate tofacitinib well, risks exist.

The FDA has approved tofacitinib for conditions like rheumatoid arthritis and ulcerative colitis, suggesting it is safe for these uses. However, its use for Sjogren's syndrome remains under investigation. Participants should consider the potential benefits and risks before joining a trial. Consulting a healthcare provider is essential before making a decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Sjogren's syndrome?

Most treatments for Sjogren's Syndrome focus on managing symptoms, like artificial tears for dry eyes or medications to increase saliva production. But tofacitinib works differently, targeting the immune system to reduce inflammation. It inhibits Janus kinase (JAK) enzymes, which play a key role in the inflammatory process. Researchers are excited about tofacitinib because it could address the underlying causes of Sjogren's Syndrome rather than just alleviating symptoms, potentially offering a more comprehensive treatment approach.

What evidence suggests that tofacitinib might be an effective treatment for Sjogren's syndrome?

Research has shown that tofacitinib, which participants in this trial may receive, might help people with Sjogren's syndrome. In one study, 80% of patients taking tofacitinib experienced at least a one-point or 15% improvement in their ESSPRI scores, which measure symptoms like pain and tiredness. Another study found that inflammation markers, such as C reactive protein (CRP), dropped by 20% or more. These results suggest that tofacitinib could help reduce symptoms and inflammation in people with Sjogren's syndrome. ^{1 3 6 7 8}

Who Is on the Research Team?

Blake M Warner, D.D.S.

Principal Investigator

National Institute of Dental and Craniofacial Research (NIDCR)

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Drug: Tofacitinib Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

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+

Published Research Related to This Trial

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, 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]

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]

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]

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 (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]

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 (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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10676577/

Tofacitinib in the treatment of primary Sjögren's syndrome ...

This study will be the first randomized controlled trial to investigate tofacitinib compared to the traditional regimen of CYC in combination with AZA in the ...

2.

academic.oup.com

academic.oup.com/rheumatology/advance-article-abstract/doi/10.1093/rheumatology/keaf173/8096387

Evaluating the therapeutic potential of tofacitinib in Sjögren's ...

In total, 80% (8/10) of patients achieved a decrease of at least one point or 15% in ESSPRI scores. A significant reduction in the proportion of ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04496960

NCT04496960 | Safety of Tofacitinib, an Oral Janus Kinase ...

To assess clinical improvement after treatment with Tofacitinib as measured by changes in the European League Against Rheumatism (EULAR) Sjogren's syndrome ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S152169422500052X

Novel therapies in Sjögren's disease: A systematic review ...

Responders to each therapeutic were defined as patients who experienced ≥20 % improvement in C reactive protein (CRP) levels and ≥20 % ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9895869/

JAK/STAT Pathway Targeting in Primary Sjögren Syndrome

In exploratory analyses, the salivary rate and tear production resulted stabilized at similar levels compared with baseline during the treatment with filgotinib ...

6.

academic.oup.com

academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keaf173/8096387

Evaluating the therapeutic potential of tofacitinib in Sjögren's ...

In cohort ǀ, 112 patients treated with tofacitinib showed a significant improvement in the ESSDAI score (median [IQR], 8.00 (4.25, 15.75) vs ...

7.

ard.bmj.com

ard.bmj.com/content/83/11/1561

Safety and efficacy of tofacitinib for the treatment of patients ...

Results Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1–103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients ...

8.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1567576920302460

The off-label uses profile of tofacitinib in systemic ...

Tofacitinib has been approved by the FDA to be used in the treatments of rheumatoid arthritis, psoriatic arthritis, plaque psoriasis and ulcerative colitis.