Trial Outcomes & Findings for Pilot Trial of Ustekinumab for Primary Sjögren's Syndrome (NCT NCT04093531)

Last Updated: 2024-06-25

Results Overview

The primary endpoint is a well-established, patient reported questionnaire for use in PSS, the ESSPRI. The ESSPRI is composed of 3 scales - dryness, fatigue, and pain. Each scale is measured 0 - 10, 0 being no symptoms, 10 being maximal imaginable dryness, fatigue or pain. The total score is the mean score of the three scales which ranges from 0- 10. Baseline ESSPRI total score will be compared to week 24, end of treatment, ESSPRI total score.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

baseline to 24 weeks

Results posted on

2024-06-25

Participant Flow

12 subjects were consented. 4 failed screening.

Participant milestones

Participant milestones
Measure	Ustekinumab All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel. Ustekinumab: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Overall Study STARTED	12
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Ustekinumab All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel. Ustekinumab: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Overall Study failed screening	4

Baseline Characteristics

Pilot Trial of Ustekinumab for Primary Sjögren's Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ustekinumab n=8 Participants All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel. Ustekinumab: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Age, Continuous	47.3 years n=93 Participants
Sex: Female, Male Female	8 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	8 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	8 participants n=93 Participants

PRIMARY outcome

Timeframe: baseline to 24 weeks

Outcome measures

Outcome measures
Measure	Ustekinumab n=8 Participants All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel. Ustekinumab: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Change in The European League Against Rheumatism (EULAR) Sjogren's Syndrome Patient Reported Index (ESSPRI) Score From Baseline to Week 24	-0.125 score on a scale Interval -1.0 to 2.0

SECONDARY outcome

Timeframe: baseline to 24 weeks

The SF-36 is a measure of health-related quality-of-life. It's a 36-item patient-reported questionnaire that covers 8 health domains. Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state. Changes in total scores in each domain from BL to week 24 will be measured for physical function, energy/fatigue, pain and general health.

Outcome measures

Outcome measures
Measure	Ustekinumab n=8 Participants All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel. Ustekinumab: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Change in the Short Form Health Survey (SF-36) Patient Reported Outcome Measure Between Day 0 and Week 24 physical function	11.1 score on a scale Standard Deviation 8.9
Change in the Short Form Health Survey (SF-36) Patient Reported Outcome Measure Between Day 0 and Week 24 energy/fatigue	7.5 score on a scale Standard Deviation 17.9
Change in the Short Form Health Survey (SF-36) Patient Reported Outcome Measure Between Day 0 and Week 24 pain	5.25 score on a scale Standard Deviation 15.5
Change in the Short Form Health Survey (SF-36) Patient Reported Outcome Measure Between Day 0 and Week 24 general health	0.6 score on a scale Standard Deviation 20.1

SECONDARY outcome

Timeframe: baseline to 24 weeks

To determine whether the standard dosing schedule for ustekinumab lowers serum biomarkers of inflammation in patients with PSS blood will be collected at baseline and week 24 for the following mechanistic studies: Serum levels of TNFα, IL-6, IL17, IL17A, IL17F, IL22, IL12, IL23, BAFF, B and T cell, blood interferon signature.

Outcome measures

Outcome measures
Measure	Ustekinumab n=8 Participants All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel. Ustekinumab: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IFNa2	6.984 pg/mL Standard Deviation 0.2922
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IL12p40	12.62 pg/mL Standard Deviation 0.0893
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IP-10	111.3 pg/mL Standard Deviation 0.6145
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IL-17F	0.02175 pg/mL Standard Deviation 0.3683
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IFNg	-0.3912 pg/mL Standard Deviation 0.9705
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IL12p70	3.054 pg/mL Standard Deviation 0.0204
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IL-13	1.689 pg/mL Standard Deviation 0.6965
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IL17A	-1.236 pg/mL Standard Deviation 0.4774
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IL-22	0.2963 pg/mL Standard Deviation 0.2742
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IL-23	1.456 pg/mL Standard Deviation 0.1801
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 IL-6	2.411 pg/mL Standard Deviation 0.2198
Change in Mean Serum Biomarkers of Inflammation From Baseline to Week 24 TNFa	1.374 pg/mL Standard Deviation 0.1252

SECONDARY outcome

Timeframe: 24 weeks.

The ESSDAI is a disease activity measurement that has 12 domains. The score of each domain is the product of the weight of the domain by the level of activity. Lower numbers indicate less activity. The total score is the sum of the score of all domains. The total score ranges from 0-123. Mean scores at baseline and week 24 are reported.

Outcome measures

Outcome measures
Measure	Ustekinumab n=8 Participants All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel. Ustekinumab: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Total Score of the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) Baseline	2.86 score on a scale Standard Deviation 3.563
Total Score of the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) Week 24	1.75 score on a scale Standard Deviation 1.5811

Adverse Events

Ustekinumab

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Ustekinumab n=8 participants at risk All subjects will receive an intravenous loading dose of 6 mg/kg at their baseline visit. 650mg acetaminophen and 60mg allegra will be given as premedication to the infusion. All patients will receive 90mg ustekinumab by a subcutaneous injection at all subsequent dosing visits. Subcutaneous injections do not require any premedication. Drug will be administered by qualified personnel. Ustekinumab: Up to 15 subjects will receive an infusion loading dose of 6 mg/kg of ustekinumab at baseline, and 90 mg of ustekinumab subcutaneously at week 4, week 12 and week 20. Subjects will be followed for 24 weeks.
Musculoskeletal and connective tissue disorders bilateral leg pain	12.5% 1/8 • 24 weeks
General disorders chest heaviness	12.5% 1/8 • 24 weeks
Eye disorders Conjunctival Hemorrhage in right eye	12.5% 1/8 • 24 weeks
Gastrointestinal disorders Diarrhea	12.5% 1/8 • 24 weeks
Eye disorders Double Vision	12.5% 1/8 • 24 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	12.5% 1/8 • 24 weeks
Blood and lymphatic system disorders Enlarged lymph node	25.0% 2/8 • 24 weeks
Skin and subcutaneous tissue disorders Erythema right eyebrow	12.5% 1/8 • 24 weeks
General disorders Fever	25.0% 2/8 • 24 weeks
Nervous system disorders headache	12.5% 1/8 • 24 weeks
Gastrointestinal disorders abdominal pain	12.5% 1/8 • 24 weeks
Reproductive system and breast disorders menopause	12.5% 1/8 • 24 weeks
Musculoskeletal and connective tissue disorders muscle tenderness right shoudler	12.5% 1/8 • 24 weeks
Gastrointestinal disorders nausea	62.5% 5/8 • 24 weeks
Injury, poisoning and procedural complications right ankle sprain	12.5% 1/8 • 24 weeks
Skin and subcutaneous tissue disorders scalp rash	12.5% 1/8 • 24 weeks
Infections and infestations sinus infection	12.5% 1/8 • 24 weeks
Ear and labyrinth disorders vertigo	12.5% 1/8 • 24 weeks
Gastrointestinal disorders worsening GI reflux	12.5% 1/8 • 24 weeks
Vascular disorders worsening hypertension	12.5% 1/8 • 24 weeks

Additional Information

Ummara Shah, MD

University of Rochester

Phone: 585-275-1643

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place