M35 NULL NULL
Conditions
Interventions
Eligible participants will be randomized on Day 1 in a 1:1:1 ratio using IRT to 1 of the following 3 treatment groups for a duration of 52 weeks: DEUC 3 mg BID - Eligible participants will be randomiz
Sponsors
Bristol Myers Squibb Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key inclusion criteria (English): 1)Signed Written Informed Consent a) Participants must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form (ICF) in accordance with regulatory, local, and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care. 2) Type of Participant and Target Disease Characteristics a) Participants meeting 2016 ACR/EULAR Classification Criteria for SjS with disease duration (from time of diagnosis) of at least 16 weeks prior to screening. i) If a prior labial or parotid gland biopsy was performed, this information will be reported in the Case Report Form (CRF), and the biopsy report should be obtained for the source documents. b) Disease duration since diagnosis of SjS = 10 years before screening. c) ESSDAI score of = 5 (moderate to severe disease, including disease activity from the following domains: articular, cutaneous, glandular, lymphadenopathy, renal, constitutional, biologic, and/or hematologic) at screening. Note: Participants may have activity in the other 4 domains (ie, central nervous system, peripheral nervous system, pulmonary system, and muscular systems). However, these domains will not be counted towards eligibility. The complete ESSDAI (12 domains) score will be used for stratification and to assess disease activity in the study. d) Positive anti-Ro/SSA at screening. e) A stimulated whole salivary flow of = 0.05 mL/min at screening or unstimulated whole saliva secretion = 0.01 mL/min at screening. 3) Age of Participant a) Participant must be at least 18 years or local age of majority at the time of signing the ICF. 4) Reproductive Status • Investigators shall counsel women of childbearing potential (WOCBP) participants (as defined in Appendix 4) and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. • The investigator shall evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. • Local laws and regulations may require the use of alternative and/or additional contraception methods. a) Female Participants: i) Female participants who are not of childbearing potential must have documented proof. Note: Documentation can come from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview. (1) Women who are not of childbearing potential (as defined in Appendix 4) are exempt from contraceptive requirements. ii) WOCBP must have a negative highly sensitive serum pregnancy test at screening visit and a negative highly sensitive urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study intervention. •If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. • Additional requirements for pregnancy testing during and after study intervention are in Section 2: Schedule of Activities. • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to potentially decrease the risk for inclusion of a woman with an undetected pregnancy. iii) WOCBP must
Exclusion criteria
Exclusion criteria: 1) Target Disease Exclusions a) Participants who have a systemic autoimmune disease other than SjS, such as rheumatoid arthritis, SLE, or systemic sclerosis, that can better explain the majority of the symptoms (eg, secondary Sjögren’s syndrome). b) Participants who have another autoimmune disease or inflammatory condition that could interfere with assessment of response of SjS to therapy (eg, IgG4-related disease, systemic sclerosis, inflammatory bowel disease). c) Participants with any other medical condition associated with sicca syndrome (eg, history of head and neck radiation treatment, sarcoidosis, chronic graft-versus-host disease). Participants with sicca symptoms secondary to ongoing medication use based on the investigator’s assessment are to be excluded. d) Active fibromyalgia with pain symptoms or signs that would interfere with joint assessment or requiring adjustment in medication within the 3 months before screening to control symptoms; participants with fibromyalgia that is well controlled on stable treatment may otherwise be considered. e) Severe complications of SjS at the time of screening, including, but not restricted to, the following: i) Vasculitis with renal, digestive, cardiac, pulmonary, or central nervous system (CNS) involvement characterized as severe (Note: cutaneous vasculitis is allowed). ii) Active CNS or peripheral nervous system (PNS) involvement requiring high-dose steroids (> 10 mg/day prednisone or equivalent). iii) Renal disease including, but not limited to, the following: (1) Proliferative glomerulonephritis requiring high-dose steroids (> 10 mg/day prednisone or equivalent) or cytotoxic agents. (2) Nephrotic syndrome with proteinuria > 3 g/day or urine protein:creatinine ratio (UPCR) > 339 mg/mmol. Participants with prior, controlled renal disease with current serum creatinine = 2× upper limit of normal (ULN) and either residual proteinuria up to 3 g/day or a UPCR of 3 mg/mg or 339 mg/mmol are allowed. Control of renal disease must be documented with at least 2 measurements of proteinuria or UPCR over the past 6 months. iv) Severe pulmonary disease based on the investigator’s assessment. Note: Participant must not have shortness of breath at rest. v) Active myositis requiring more than the maximum dose of corticosteroids (> 10 mg/day prednisone or equivalent). 2) General Medical Conditions and History a) Any major illness/condition or evidence of an unstable clinical condition (eg, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, immunologic, psychiatric) or local active infection/infectious illness that, in the investigator’s judgment, will substantially increase the risk to the participant if he/she participates in the study. b) Any major surgery within the last 30 days prior to randomization, or any surgery planned for the first 52 weeks of the study. c) Participants with cancer or history of cancer within the previous 5 years except for: i) Treated (eg, cured) basal cell or squamous cell in situ skin carcinomas. ii) Treated (eg, cured) cervical intraepithelial neoplasia or carcinoma in situ of the cervix with no evidence of recurrence within 5 years of the screening visit. d) Any history of lymphoproliferative disease including prelymphoma (pseudolymphoma of the orbit and small intestine, lymphomatoid granulomatosis, angioimmunoblastic lymphadenopathy, and lymphoid interstitial pneumonitis). e) Acute coronary syndrome (eg, myocardial infarction, unstable angina pectoris)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in ESSDAI at Week 52 NAME OF THE RESULT: To compare the efficacy of DEUC versus PBO in participants with active SjS by ESSDAI improvement at Week 52 PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| ESSDAI i. Change from baseline in ESSDAI over time (by visit) up to Week 52 ii. Percentage (%) of participants with decrease in ESSDAI = 3 points from baseline over time (by visit) up to Week 52 iii. Percentage (%) of participants with ESSDAI 0 at baseline/Any change in UWSF if score = 0 at baseline OR Decrease of gland ultrasonography = 25% v) 1 point: Decrease of RF = 25% OR Decrease of IgG = 10% • Change from baseline in DAS28-CRP over time (by visit) up to Week 52 • Change from baseline in CDAI over time (by visit) up to Week 52 • Proportion of participants meeting achievement of total CRESS response over time (by visit) up to Week 52 where total CRESS response is defined as response on at least 3 of the 5 following items: i) ClinESSDAI 0 at baseline/Any change in UWSF if score = 0 at baseline OR Decrease of gland ultrasonography = 25% v. 1 point: Decrease of RF = 25% OR Decrease of IgG = 10% • Change from baseline in DAS28-CRP at Week 104, Week 156, and over time (by visit) • Change from baseline in CDAI at Week 104, Week 156, and over time (by visit) • Proportion of participants meeting achievement of total CRESS response at Week 104, Week 156, and over time (by visit) where total CRESS response is defined as response on at least 3 of the 5 following items: i) ClinESSDAI < 5 points ii) Decrease of ESSPRI = 1 point or 15% iii) Increase of Schirmer's test = 5 mm if abnormal baseline/No change of Schirmer's test to abnormal if normal baseline OR Decrease of OSS = 2 if abnormal baseline/No change of OSS to abnormal if normal baseline iv) Increase of UWSF = 25% OR Decrease of gland ultrasonography = 25% v) Decrease of RF = 25% OR Decrease of IgG = 10% NAME OF THE RESULT: Disease Activity: To compare the efficacy of DEUC versus PBO in participants with active SjS based on disease activity at Week 104, Week 156, and over time (by visit) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Until the end of study;Ch | — |
Countries
Argentina, Brazil, Bulgaria, Canada, China, Colombia, France, Germany, Hong Kong, Ireland, Italy, Korea South, Lithuania, Mexico, Peru, Poland, Romania, Turkey, United States
Contacts
Public ContactJACKELYN ELENA BORJA
BRISTOL-MYERS SQUIBB PERU S.A.
Outcome results
None listed