A Study to Evaluate the Efficacy and Safety of Telitacicept in Subjects With Active Primary Sjogren's Syndrome

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of subcutaneous Telitacicept versus placebo in subjects with active primary Sjogren's Syndrome.

Detailed Description
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This is a phase Ⅲ, multi-center, randomized, placebo-controlled, study. Subjects with active primary Sjogren's Syndrome (pSS) will be randomized to receive subcutaneous Telitacicept 80 mg, Telitacicept 160 mg or placebo weekly for a total of 48 weeks. Subjects are allowed to be transferred to another group after Week 24 by the investigator so that those randomized to the placebo group are able to receive either Telitacicept 80 mg or Telitacicept 160 mg afterwards. Subjects who are randomized to Telitacicept 80 mg and Telitacicept 160 mg groups will remain in the previous treatment group even if the investigator chooses to transfer them. Subjects and investigators are blinded throughout the study.

Official Title
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A Phase Ⅲ, Multi-center, Randomized, Placebo-controlled, Study to Evaluate the Efficacy and Safety of Subcutaneous Telitacicept in Subjects With Active Primary Sjogren's Syndrome

Conditions
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Primary Sjogren's Syndrome

Intervention / Treatment
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* Biological: Telitacicept 80 mg
* Biological: Telitacicept 160 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Written informed consent provided. Males and females, 18-70 years of age. Fulfilled the classification criteria of pSS according to ACR/EULAR (2016). Anti-SSA antibody tested positive at screening. ESSDAI score ≥ 5 at screening. Main Exclusion Criteria: Secondary Sjogren's syndrome. Severe organ involvement related to pSS in the opinion of the investigator, including but not limited to a) severe vasculitis (not cutaneous vasculitis) affecting the kidney, gastrointestinal system, cardiac, pulmonary or central nervous system (CNS); b) active CNS or peripheral nervous system involvement requiring high dose corticosteroids; c) severe kidney involvement, e.g. GFR < 60 ml/min, serum creatinine > 2 mg/dL, or proteinuria > 3g/d; d) severe pulmonary involvement, e.g. shortness of breath at rest, FVC < 60% or DLCO < 40%; e) muscle diseases requiring high dose corticosteroids; f) lymphoma. Received sodium hyaluronate eye drops, artificial tears or artificial saliva within 7 days prior to screening. Received live vaccine within 28 days prior to randomization. Active hepatitis or history of severe liver diseases. HIV positive. Patients with malignant tumors. Received investigational pharmaceutical within 28 days or 5 half-lives prior to randomization, whichever is longer. Nursing or pregnant female, or male or female who prepared for parenthood during the study. Any condition that, in the opinion of the investigator, makes it unsuitable for the subject to participate, e.g., poorly controlled high blood pressure, diabetes, heart failure or mental illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telitacicept 80 mg<br>Subjects will be given subcutaneous Telitacicept 80 mg once a week for 48 weeks. | Biological: Telitacicept 80 mg<br>* Telitacicept 80 mg subcutaneously once a week.<br>* Other names: RC 18 80 mg;|
| Experimental: Telitacicept 160 mg<br>Subjects will be given subcutaneous Telitacicept 160 mg once a week for 48 weeks. | Biological: Telitacicept 160 mg<br>* Telitacicept 160 mg subcutaneously once a week.<br>* Other names: RC 18 160 mg;|
| Placebo Comparator: Placebo<br>Subjects will be given subcutaneous placebo once a week for 24-48 weeks. Subjects who are randomized to the placebo group are allowed to be transferred to either Telitacicept 80 mg or Telitacicept 160 mg after Week 24 by the investigator. Subjects and investigators are blinded throughout the study. | Drug: Placebo<br>* Subjects will be given subcutaneous placebo once a week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ESSDAI score | The EULAR Sjogren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. It includes 12 domains (ie, organ systems: cutaneous, respiratory, renal, articular, muscular, peripheral nervous system (PNS), central nervous system (CNS), haematological, glandular, constitutional, lymphadenopathic, biological). Each domain is divided into 3-4 levels of activity (no, low, moderate, high). Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A higher score indicates worsening of the disease. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in ESSDAI score | The EULAR Sjogren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. It includes 12 domains (ie, organ systems: cutaneous, respiratory, renal, articular, muscular, peripheral nervous system (PNS), central nervous system (CNS), haematological, glandular, constitutional, lymphadenopathic, biological). Each domain is divided into 3-4 levels of activity (no, low, moderate, high). Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A higher score indicates worsening of the disease. | Week 48 | 
| Percentage of subjects with ESSDAI score decreased from baseline by at least 3 points | The EULAR Sjogren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. It includes 12 domains (ie, organ systems: cutaneous, respiratory, renal, articular, muscular, peripheral nervous system (PNS), central nervous system (CNS), haematological, glandular, constitutional, lymphadenopathic, biological). Each domain is divided into 3-4 levels of activity (no, low, moderate, high). Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A higher score indicates worsening of the disease | Week 24 & Week 48 | 
| Percentage of subjects with ESSDAI score < 5 | The EULAR Sjogren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. It includes 12 domains (ie, organ systems: cutaneous, respiratory, renal, articular, muscular, peripheral nervous system (PNS), central nervous system (CNS), haematological, glandular, constitutional, lymphadenopathic, biological). Each domain is divided into 3-4 levels of activity (no, low, moderate, high). Overall score is calculated as sum of all individual weighted domain scores (ranges from 0 (best) to 123 (worst activity). A higher score indicates worsening of the disease. | Week 24 & Week 48 | 
| Percentage of subjects with ESSPRI score decreased from baseline by at least 1 point or 15% | The EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) is a patient-reported, subjective symptom index for primary Sjögren's syndrome. 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. | Week 24 & Week 48 | 
| Change from baseline in MFI-20 | The multidimensional fatigue inventory (MFI-20) is a 20-item self-report instrument designed to measure fatigue. It covers the following dimensions: general fatigue, physical fatigue, reduced activity, reduced motivation and mental fatigue. Each question is scored from one to five and each dimension consists of five questions. The dimensional score consequently ranges from 4 to 20 (a higher score indicates more fatigue). | Week 24 & Week 48 | 
| Incidence of AEs, SAEs | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death; is life-threatening experience; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or is a congenital anomaly/ birth defect; or any other important medical event that may not be immediately life-threatening or result in death or hospitalization but may require intervention to prevent one of the other serious outcomes listed in the definition above. | Up to Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pSS, primary Sjogren's Syndrome, RC18