Trial Outcomes & Findings for Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Primary Sjogren's Syndrome (NCT NCT04496960)

NCT ID: NCT04496960

Last Updated: 2025-12-18

Results Overview

Count of adverse events by grade was assessed using the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to adverse event. Serious is defined as any grade 3 or higher adverse event. Toxicity is defined as any study drug-related Grade 3 or higher adverse event.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1/PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Up to day 196

Results posted on

2025-12-18

Participant Flow

23 Participants were consented * 12 participants started the study * 11 participants were screen failure

Participant milestones

Participant milestones
Measure
Drug: Tofacitinib
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Overall Study
STARTED
8
4
Overall Study
COMPLETED
8
3
Overall Study
NOT COMPLETED
0
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Drug: Tofacitinib
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Overall Study
Physician Decision
0
1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Drug: Tofacitinib
n=8 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=4 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Total
n=12 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=47 Participants
0 Participants
n=41 Participants
0 Participants
n=88 Participants
Age, Categorical
Between 18 and 65 years
7 Participants
n=47 Participants
3 Participants
n=41 Participants
10 Participants
n=88 Participants
Age, Categorical
>=65 years
1 Participants
n=47 Participants
1 Participants
n=41 Participants
2 Participants
n=88 Participants
Sex: Female, Male
Female
8 Participants
n=47 Participants
4 Participants
n=41 Participants
12 Participants
n=88 Participants
Sex: Female, Male
Male
0 Participants
n=47 Participants
0 Participants
n=41 Participants
0 Participants
n=88 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
n=47 Participants
0 Participants
n=41 Participants
2 Participants
n=88 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants
n=47 Participants
4 Participants
n=41 Participants
10 Participants
n=88 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=47 Participants
0 Participants
n=41 Participants
0 Participants
n=88 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=47 Participants
0 Participants
n=41 Participants
0 Participants
n=88 Participants
Race (NIH/OMB)
Asian
1 Participants
n=47 Participants
0 Participants
n=41 Participants
1 Participants
n=88 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=47 Participants
0 Participants
n=41 Participants
0 Participants
n=88 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=47 Participants
0 Participants
n=41 Participants
0 Participants
n=88 Participants
Race (NIH/OMB)
White
6 Participants
n=47 Participants
4 Participants
n=41 Participants
10 Participants
n=88 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=47 Participants
0 Participants
n=41 Participants
1 Participants
n=88 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=47 Participants
0 Participants
n=41 Participants
0 Participants
n=88 Participants

PRIMARY outcome

Timeframe: Up to day 196

Population: Intent to treat population

Count of adverse events by grade was assessed using the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to adverse event. Serious is defined as any grade 3 or higher adverse event. Toxicity is defined as any study drug-related Grade 3 or higher adverse event.

Outcome measures

Outcome measures
Measure
Drug: Tofacitinib
n=33 Count of adverse events
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=12 Count of adverse events
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Number of Adverse Events by Grade/Category
Grade 1
19 Count of adverse events
3 Count of adverse events
Number of Adverse Events by Grade/Category
Grade 2
10 Count of adverse events
7 Count of adverse events
Number of Adverse Events by Grade/Category
Grade 3
4 Count of adverse events
2 Count of adverse events
Number of Adverse Events by Grade/Category
Grade 4
0 Count of adverse events
0 Count of adverse events
Number of Adverse Events by Grade/Category
Grade 5
0 Count of adverse events
0 Count of adverse events
Number of Adverse Events by Grade/Category
Serious
4 Count of adverse events
1 Count of adverse events
Number of Adverse Events by Grade/Category
Toxicity
4 Count of adverse events
0 Count of adverse events

PRIMARY outcome

Timeframe: Up to day 196

Population: Intent to treat population

Number participants with any adverse events by grade and severity was assessed using the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental activity of daily living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event. Serious is defined as any grade 3 or higher adverse event. Toxicity is defined as any study drug-related Grade 3 or higher adverse event.

Outcome measures

Outcome measures
Measure
Drug: Tofacitinib
n=8 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=4 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Participants With Adverse Events
Subjects with at least one adverse event
7 Participants
3 Participants
Participants With Adverse Events
Subjects with at least one adverse event with grade 3 and above
1 Participants
1 Participants
Participants With Adverse Events
Subjects with at least one Severe adverse event (SAE)
1 Participants
1 Participants
Participants With Adverse Events
Subjects with at least one toxicity
1 Participants
0 Participants

SECONDARY outcome

Timeframe: Day 168 minus day 1

Population: Intent to treat population

The Physician Global Activity (PGA) is a subjective physician reported disease activity index that uses a 10-cm Visual Analog Scale (VAS) to score a patient's disease activity. The 10-cm visual analogue scale (VAS) was scored by a physician with a vertical line on the scale marking disease activity where 0 cm indicates no evidence of disease activity, and 10 cm indicates severe disease activity, with score reported on a scale from 0-10. Higher score indicates more disease activity. Change in disease activity index was measured as the mean difference in disease activity scores between time points. Data was analyzed as the change in score between day 1 (baseline) and study day 168 (Change = day 168 - day 1) for the treatment/placebo groups as repeated measures.

Outcome measures

Outcome measures
Measure
Drug: Tofacitinib
n=8 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=3 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Change in Physicians Global Assessment (PGA) Score
0 Units on a scale
Standard Deviation 3.07
-1.67 Units on a scale
Standard Deviation 2.89

SECONDARY outcome

Timeframe: Day 168 minus day 1

Population: Intent to treat population

The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index designed to measure disease activity in patients with primary SS. It includes 12 organ domains (e.g., constitutional, glandular, neurological) for disease activity, each with a 4-point scale (0 = No activity; 3=High activity). These scores are then multiplied by domain-specific weights (1-6) and summed to produce a total score ranging from 0 to 123, with higher scores indicating greater disease activity. Data was analyzed as the change in score between day 1 (baseline) and study day 168 (Change = day 168 - day 1) for the treatment/placebo groups as repeated measures.

Outcome measures

Outcome measures
Measure
Drug: Tofacitinib
n=8 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=3 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Change in EULAR Sjögren's Syndrome (SS) Disease Activity Index (ESSDAI) Score
-0.13 Units on a scale
Standard Deviation 1.13
-1.33 Units on a scale
Standard Deviation 2.31

SECONDARY outcome

Timeframe: Day 168 minus day 1

Population: Intent to treat population

Changes in salivary flow was assessed by measuring whole unstimulated saliva flow (WUS) and glandular parotid and submandibular/sublingual unstimulated and 0.2% citric acid stimulated flow rates using ultrasonograph. Validated scoring criteria was used to assess ultrasonographic feature parameters at baseline and at the study day 168. Data was analyzed as the change in score between day 1 (baseline) and study day 168 (Change = day 168 - day 1) for the treatment/placebo groups as repeated measures.

Outcome measures

Outcome measures
Measure
Drug: Tofacitinib
n=8 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=3 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Change in Whole Unstimulated Saliva Flow
-0.13 ml/min/gland
Standard Deviation 1.13
-1.33 ml/min/gland
Standard Deviation 2.31

SECONDARY outcome

Timeframe: Day 168 minus day 1

Population: Intent to treat population

Changes in salivary flow was assessed by measuring whole stimulated saliva flow and glandular parotid and submandibular/sublingual stimulated and 0.2% citric acid stimulated flow rates using ultrasonograph. Validated scoring criteria was used to assess ultrasonographic feature parameters at baseline and at the study day 168. Data was analyzed as the change in score between day 1 (baseline) and study day 168 (Change = day 168 - day 1) for the treatment/placebo groups as repeated measures.

Outcome measures

Outcome measures
Measure
Drug: Tofacitinib
n=8 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=3 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Change in Whole Stimulated Saliva Flow
10.6 ml/min/gland
Standard Deviation 1.13
6.21 ml/min/gland
Standard Deviation 2.31

SECONDARY outcome

Timeframe: Day 168 minus day 1

Population: Intent to treat population

The EULAR Sjögren's Syndrome (SS) Patient Reported Index (ESSPRI) is a patient-reported outcome measure (PROM) that focuses on the subjective experience of symptoms in SS. The tool assesses the key symptoms of dryness, pain and fatigue. A single 0-10 numerical scale is used to assess each of these symptoms. Final score is the average of the scores from the three domains. A final ESSPRI score of less than 5 is considered indicative of acceptable disease status, while a score of 5 or higher suggests high disease activity. Questionnaire was completed at baseline and day 168. Data was analyzed as

Outcome measures

Outcome measures
Measure
Drug: Tofacitinib
n=8 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=3 Participants
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Change in EULAR Sjögren's Syndrome (SS) Patient Reported Index (ESSPRI)
-1.33 Units on a scale
Standard Deviation 2.04
0.78 Units on a scale
Standard Deviation 0.51

Adverse Events

Drug: Tofacitinib

Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths

Placebo

Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Drug: Tofacitinib
n=8 participants at risk
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=3 participants at risk
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Investigations
Neutrophil count decreased
12.5%
1/8 • Up to day 196
33.3%
1/3 • Up to day 196

Other adverse events

Other adverse events
Measure
Drug: Tofacitinib
n=8 participants at risk
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive tofacitinib 5 mg orally twice daily for 168 days.
Placebo
n=3 participants at risk
Sjogren's Disease (SjD) patients with mild to moderate disease activity receive placebo orally twice daily for 168 days.
Surgical and medical procedures
Spinal fusion surgery
0.00%
0/8 • Up to day 196
33.3%
1/3 • Up to day 196
Infections and infestations
Vaginal infection
0.00%
0/8 • Up to day 196
33.3%
1/3 • Up to day 196
Injury, poisoning and procedural complications
Barotrauma
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Investigations
Neutrophil count decreased
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Musculoskeletal and connective tissue disorders
Arthralgia
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Musculoskeletal and connective tissue disorders
Back pain
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Musculoskeletal and connective tissue disorders
Myalgia
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Nervous system disorders
Headache
0.00%
0/8 • Up to day 196
33.3%
1/3 • Up to day 196
Respiratory, thoracic and mediastinal disorders
Nasal congestion
0.00%
0/8 • Up to day 196
33.3%
1/3 • Up to day 196
Respiratory, thoracic and mediastinal disorders
Reflux laryngitis
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
62.5%
5/8 • Up to day 196
33.3%
1/3 • Up to day 196
Skin and subcutaneous tissue disorders
Rash maculo-papular
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Gastrointestinal disorders
Abdominal pain
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Gastrointestinal disorders
Diarrhoea
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Gastrointestinal disorders
Nausea
0.00%
0/8 • Up to day 196
33.3%
1/3 • Up to day 196
Gastrointestinal disorders
Salivary gland calculus
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Gastrointestinal disorders
Vomiting
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Immune system disorders
Allergy to arthropod sting
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Infections and infestations
Herpes simplex reactivation
0.00%
0/8 • Up to day 196
33.3%
1/3 • Up to day 196
Infections and infestations
BK virus infection
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Infections and infestations
Conjunctivitis
0.00%
0/8 • Up to day 196
33.3%
1/3 • Up to day 196
Infections and infestations
Oral candidiasis
12.5%
1/8 • Up to day 196
33.3%
1/3 • Up to day 196
Infections and infestations
Otitis media
12.5%
1/8 • Up to day 196
0.00%
0/3 • Up to day 196
Infections and infestations
Urinary tract infection
25.0%
2/8 • Up to day 196
0.00%
0/3 • Up to day 196

Additional Information

Dr. Blake Warner

National Institute of Dental and Craniofacial Research

Phone: +1 301 500 8063

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place