A Study of INCB050465 in Primary Sjögren's Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to assess the impact of parsaclisib on the signs and symptoms of Sjögren's syndrome (SS).

Official Title
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An Open-Label Phase 2 Study of INCB050465 in Participants With Primary Sjögren's Syndrome

Conditions
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Primary Sjögren's Syndrome

Intervention / Treatment
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* Drug: Parsaclisib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary SS diagnosed according to the revised American-European Consensus Group (AECG) criteria. Minimum score of 2 on the SGUS score for parotid and submandibular glands. EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ≥ 5. Positive serum titers of anti-SS-A and/or anti-SS-B antibodies. Symptomatic oral dryness score of at least 5 on patient questionnaire. Willingness to avoid pregnancy or fathering children based on protocol-defined criteria. Exclusion Criteria: Diagnosis of secondary SS according to the revised AECG criteria (eg, the presence of a previously diagnosed or a present diagnosis of rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, polymyositis, dermatomyositis, immunoglobulin G4-related disorder, sarcoidosis, or any other defined autoimmune rheumatologic disorder). Concurrent conditions and history of other diseases per protocol-defined criteria. Positive test results for tuberculosis (TB) from the QuantiFERON-TB Gold test or T-spot.TB test. Positive serology test results for HIV antibody, hepatitis B surface antigen, hepatitis B surface antigen antibody, HBV core antibody, or HCV (HCV antibody with positive HCV-RNA). Severely impaired liver function (Child-Pugh Class C). Prior or ongoing therapy with protocol-defined drugs. Receipt of any live vaccine in the 30 days before screening. No major surgery within 30 days before screening. Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy. Current alcohol or drug use that, in the opinion of the investigator, will interfere with the participant's ability to comply with the dose regimen and study evaluations. Laboratory values at screening outside the protocol-defined ranges.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Parsaclisib<br> | Drug: Parsaclisib<br>* Parsaclisib administered orally once daily at the protocol-defined dose.<br>* Other names: INCB050465;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With a 1 Point or Greater Change on the Salivary Gland Ultrasound (SGUS) Score for Parotid and Submandibular Glands | The SGUS is a combination of the scores of the 4 salivary glands (2 parotid and 2 submandibular) each gland is scored on a 5-point scale (0 to 4; 4 being more severe), with the maximum total score being 16. | Week 4 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Salivary CXCL13 Levels | To assess the impact of parsaclisib on salivary CXCL13. | Baseline, Week 4 and Week 12 | 
| Number of Participants With Treatment-emergent Adverse Events | Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to 21 weeks | 
| Change in Whole Salivary Flow | Defined as change in stimulated and unstimulated whole salivary flow from baseline | Baseline, Weeks 4, 8, and 12 | 
| Change in EULAR Sjögren's Syndrome Disease Activity Index | Defined as change in ESSDAI. The ESSDAI is a physician-assessed disease activity index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of 44 items in 12 organ-specific 'domains' contributing to disease activity (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. An overall score is then calculated as the sum of all individual weighted domain scores. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). | Week 12 | 
| Change in EULAR Sjögren's Syndrome Patient Reported Index | Defined as Change in ESSPRI. EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. | Weeks 4, 8, and 12 | 
| Change in Symptom Scores for Dryness | Defined as change in symptom scores for dryness of eyes, mouth, and vagina. The dryness questionnaire will ask participants to rate the dryness of eyes, mouth, or vagina (female participants only) with 24-hour recall using an 11-point numerical rating system ranging from 0 (no dryness) to 10 | Weeks 4, 8, and 12. | 
| Patient Global Impression of Change Questionnaire | Defined as proportions of participants in each PGIC category. The PGIC asks a single question regarding how the patient is feeling since beginning new therapy. The questionnaire uses a 7-point scale (from 1 to 7), ranging from very much improved, 1 to very much worse, 7 | Baseline, Weeks 4, 8, and 12 | 
| Change in PROMIS Fatigue Short Form | Defined as change in PROMIS Fatigue short form. The PROMIS fatigue short form includes 7 items with a rating scale of 1 to 5, 1 being no fatigue and 5 being severe fatigue. The recall period is 7 days. | Weeks 4, 8, and 12 | 
| Female Participants Only : Change in Female Sexual Function Index | Defined as change in FSFI. The FSFI is a brief, self-report measure of female sexual function (female participants only). The questionnaire contains 19 item sexual functioning questionnaire to rate sexual function between 2.0 and 36.0, where 2.0 is low sexual function and 36.0 is high sexual function. Difference in FSFI scores are reported. | Weeks 4, 8, and 12 | 
| Change in European Quality of Life 5 Dimensions Questionnaire | Defined as change in EQ-5D. The EQ-5D is a standardized measure of health status. It consists of 5 questions, each with a 5-item rating scale plus a visual analog scale rating from 1 to 100 for overall health status. Higher score represents more severe symptoms. | Weeks 4, 8, and 12 | 
| Percentage Change in Whole Salivary Flow | Defined as change and percent change in stimulated and unstimulated whole salivary flow from baseline | Baseline, Weeks 4, 8, and 12 | 
| Percentage Change in EULAR Sjögren's Syndrome Disease Activity Index | Defined as percent change in ESSDAI. The ESSDAI is a physician-assessed disease activity index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of 44 items in 12 organ-specific 'domains' contributing to disease activity (constitutional, lymphadenopathy, articular, muscular, cutaneous, glandular, pulmonary, renal, peripheral nervous system, central nervous system, hematological, biological). Each domain is assessed for activity level (i.e., no, low, moderate, high) and assigned a numerical score based on pre-determined weighting of each individual domain. An overall score is then calculated as the sum of all individual weighted domain scores. Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). | Week 12 | 
| Percentage Change in EULAR Sjögren's Syndrome Patient Reported Index | Defined as percentage change in ESSPRI. EULAR Sjogren's Syndrome Patient-Reported Index (ESSPRI) Score is defined as the change in score between baseline (Week -1) and Week 12. The ESSPRI is a patient-reported, subjective symptom index for primary Sjögren's syndrome developed by the EULAR consortium. It consists of three questions covering the cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain (articular and/or muscular). Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and an overall score is calculated as the mean of the three individual domains where all domains carry the same weight. | Weeks 4, 8, and 12 | 
| Percentage Change in Symptom Scores for Dryness | Defined as percent change in symptom scores for dryness of eyes, mouth, and vagina. The dryness questionnaire will ask participants to rate the dryness of eyes, mouth, or vagina (female participants only) with 24-hour recall using an 11-point numerical rating system ranging from 0 (no dryness) to 10 | Weeks 4, 8, and 12. | 
| Percentage Change in PROMIS Fatigue Short Form | Defined as percent change in PROMIS Fatigue short form. The PROMIS fatigue short form includes 7 items with a rating scale of 1 to 5, 1 being no fatigue and 5 being severe fatigue. The recall period is 7 days. | Weeks 4, 8, and 12 | 
| Female Participants Only : Percentage Change in Female Sexual Function Index | Defined as percent change in FSFI. The FSFI is a brief, self-report measure of female sexual function (female participants only). The questionnaire contains 19 item sexual functioning questionnaire to rate sexual function between 2.0 and 36.0, where 2.0 is low sexual function and 36.0 is high sexual function. Difference in FSFI scores are reported. | Weeks 4, 8, and 12 | 
| Percentage Change in European Quality of Life 5 Dimensions Questionnaire | Defined as percent change in EQ-5D. The EQ-5D is a standardized measure of health status. It consists of 5 questions, each with a 5-item rating scale plus a visual analog scale rating from 1 to 100 for overall health status. Higher score represents more severe symptoms. | Weeks 4, 8, and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Sjögren's syndrome, PI3Kδ inhibitor