Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren's Syndrome
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04496960|
Recruitment Status : Recruiting
First Posted : August 4, 2020
Last Update Posted : June 28, 2022
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.
To evaluate the safety and tolerance of tofacitinib in people with SS.
Adults ages 18-75 with SS.
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.
|Condition or disease||Intervention/treatment||Phase|
|Sjogren's Syndrome||Drug: tofacitinib Other: Placebo||Phase 1 Phase 2|
As a primary objective, this study represents an innovative investigative measure of the safety and tolerability of JAK inhibition in participants with primary Sj(SqrRoot)(Delta)gren'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.
-To determine the safety and tolerability of Tofacitinib in participants with SS and mild to moderate disease activity.
- To assess clinical improvement after treatment with Tofacitinib as measured by changes in the European League Against Rheumatism (EULAR) Sj(SqrRoot)(Delta)gren'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.
-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).
Preliminary assessments of clinical response will be measured
- 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.
|Study Type :||Interventional|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sj(SqrRoot)(Delta)Gren's Syndrome; a Phase Ib-IIa Placebo-controlled Clinical Trial and Associated Mechanistic Studies|
|Actual Study Start Date :||May 18, 2021|
|Estimated Primary Completion Date :||September 21, 2023|
|Estimated Study Completion Date :||September 20, 2024|
Placebo Comparator: Placebo group
white, round, film-coated tablet
Experimental: Subjects with SS
XELJANZ(R) is the citrate salt of tofacitinib. Tofacitinib citrate is a white to off-white powder with the following chemical name: (3R,4R)-4-methyl-3-(methyl-7H-pyrrolo [2,3-d]pyrimidin-4-ylamino) -beta-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-propanetricarboxylate (1:1) It is freely soluble in water and has a molecular weight of 504.5 Daltons. XELJANZ(R) is supplied for oral administration as 5 mg tofacitinib (equivalent to 8 mg tofacitinib citrate) white round, immediate-release film-coated tablet. Each tablet of XELJANZ(R) contains the appropriate amount of XELJANZ(R) as a citrate salt and the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, HPMC 2910/Hypromellose 6cP, titanium dioxide, macrogol/PEG3350, and triacetin.
- safety and tolerability of tofacitinib [ Time Frame: week 24 (end of Treatment) ]To determine the safety and tolerability of tofacitinib in subjects with SS and mild to moderate disease activity.
- ESSDAI [ Time Frame: Week 24 ]The ESSDAI was developed to be used as an outcome measure in clinical trials involving Sjogren s Syndrome patient cohorts and allows for assessment/scoring of major domain activity relevant to a SS population.
- changes in salivary flow rates [ Time Frame: week 24 ]salivary flow rates are an objective measure of organ function. Low salivary flow is a primary feature of SS and may be used as a non-invasive measure of therapeutic intervention. Studying the effects of tofacitinib versus placebo via randomized trial provides the best opportunity to show causality and association.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04496960
|Contact: Sasha D Clary||(301) firstname.lastname@example.org|
|Contact: Blake M Warner, D.D.S.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Blake M Warner, D.D.S.||National Institute of Dental and Craniofacial Research (NIDCR)|