NCT04496960

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

Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren's Syndrome; a Phase Ib-IIa Placebo-controlled Clinical Trial and Associated Mechanistic Studies

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: National Institute of Dental and Craniofacial Research (NIDCR) · NIH
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Study Description: As a primary objective, this study represents an innovative investigative measure of the safety and tolerability of JAK inhibition in participants with primary Sjogren's syndrome. Secondary objectives will include investigating the effects of Tofacitinib on target tissues (e.g., salivary glands), systemic inflammation, and on vascular function in SS participants. We also aim to identify biomarkers of response that may be useful as endpoints in future studies. Objectives: Primary Objective: -To determine the safety and tolerability of Tofacitinib in participants with SS and mild to moderate disease activity. Secondary Objectives: * To assess clinical improvement after treatment with Tofacitinib as measured by changes in the European League Against Rheumatism (EULAR) Sjogren's syndrome Disease Activity Index (ESSDAI) and no worsening on the Physician s Global assessment Scale (PGA). * To demonstrate that treatment with Tofacitinib is effective clinically and biologically in SS individuals with mild to moderate disease. * To investigate the effects of Tofacitinib on systemic biomarkers of SS as measures biological effects that can be used as outcome measures to power a larger Clinical Trial. Endpoints: Primary Endpoint: -Safety and tolerability will be measured by assessment of adverse events (AEs) and clinical safety laboratory tests throughout the study. Toxicity is defined as any study drug-related Grade 3 adverse event or higher (as measured by the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0). Secondary Endpoints: Preliminary assessments of clinical response will be measured by: * Changes in the ESSDAI score between Baseline and Day 168 (end of treatment) * Changes in the Physician's Global Assessment (PGA) scores between baseline and study day 168.

Conditions

• Sjogren's Syndrome

Interventions

Type	Name	Description
DRUG	tofacitinib	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.
OTHER	Placebo	white, round, film-coated tablet

Timeline

• Start date: 2021-05-18
• Primary completion: 2025-01-14
• Completion: 2026-09-22
• First posted: 2020-08-04
• Last updated: 2025-12-18
• Results posted: 2025-12-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study