A Study to Evaluate the Efficacy and Safety of Dazodalibep in Participants With Sjögren's Syndrome (SS) With Moderate-to-severe Systemic Disease Activity

Study Overview
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Brief Summary
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Primary Objective: To evaluate the effect of dazodalibep on systemic manifestations of Sjögren's Syndrome (SS) in participants with moderate-to-severe systemic disease activity. Secondary Objectives: To evaluate the effect of dazodalibep on patient reported outcomes (PROs) in participants with SS. To evaluate the safety and tolerability of dazodalibep in participants with SS

Official Title
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A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dazodalibep in Participants With Sjögren's Syndrome With Moderate-to-severe Systemic Disease Activity

Conditions
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Sjogren's Syndrome

Intervention / Treatment
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* Drug: Dazodalibep
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosed with Sjögren's syndrome (SS) by meeting the 2016 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) Classification Criteria. Have an European Alliance of Associations for Rheumatology Sjögren's Syndrome Disease Activity Index (ESSDAI) score of >= 5 despite symptomatic or local therapy at screening. Positive for either anti-Ro autoantibodies or rheumatoid factor (RF), or both at screening (as per the central laboratory test). Key Exclusion Criteria: Medical history of confirmed deep vein thrombosis, pulmonary embolism, or arterial thromboembolism within 2 years of screening. Active malignancy or history of malignancy within the last 5 years, except in situ carcinoma of cervix treated with apparent success with curative therapy > 12 months prior to screening OR cutaneous basal cell carcinoma following presumed curative therapy. Individuals with any severe or life-threatening cardiovascular (including vasculitis), respiratory, endocrine, gastrointestinal, hematological, psychiatric, or systemic disorder or any other condition that would place the individual at unacceptable risk of complications, interfere with evaluation of the IP, or confound the interpretation of participant safety or study results. Individuals who have a positive test for, or have been treated for, hepatitis B, hepatitis C (unless they have undergone hepatitis C antiviral treatment and have undetectable viral level of hepatitis C RNA at least 24 weeks following completion of therapy) or human immunodeficiency virus (HIV) infection. Active TB or untreated (per local guidelines) latent TB Individuals with a history of more than one episode of herpes zoster and/or any opportunistic infection in the last 12 months, and active infection requiring systemic treatment at the time of screening or through randomization, or history of more than 2 infections requiring intravenous (IV) antibiotics within 12 months prior to screening. Individuals who have received a live (attenuated) vaccine within the 4 weeks prior to randomization or plan to receive a live vaccine during their participation in the study. Last administration of experimental or investigational biologic or oral agents < 6 months prior to screening. Individuals who have had previous treatment with any biologic B-cell-depleting therapy (eg, rituximab, ocrelizumab, inebilizumab, ofatumumab, or ianalumab) within 12 months or other B-cell-targeting therapy (eg, belimumab) < 3 months prior to screening.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dazodalibep Dose 1<br>Participants will be administered dose 1 of dazodalibep by intravenous (IV) infusion. | Drug: Dazodalibep<br>* IV infusion<br>* Other names: MEDI 4920;|
| Experimental: Dazodalibep Dose 2<br>Participants will be administered dose 2 of dazodalibep by IV infusion. | Drug: Dazodalibep<br>* IV infusion<br>* Other names: MEDI 4920;|
| Placebo Comparator: Placebo<br>Participants will be administered placebo by IV infusion. | Drug: Placebo<br>* IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in European Alliance of Associations for Rheumatology Sjögren's Syndrome Disease Activity Index (ESSDAI) Score |  | At Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving ESSDAI response |  | At Week 48 | 
| Change from baseline in Diary for Assessing Sjogren's Patient-Reported Outcome Index (DASPRI) dryness domain score |  | At Week 48 | 
| Change from baseline in ESSPRI dryness domain score |  | At Week 48 | 
| Change from baseline in tender and swollen joint counts |  | At Week 48 | 
| Change from baseline in Patient-Reported Outcomes Measurement Information System Fatigue-Short Form 10a (PROMIS-Fatigue-SF-10a) |  | At Week 48 | 
| Change from baseline in ESSDAI score |  | Week 12 and Week 24 | 
| Change from baseline in DASPRI total score |  | At Week 48 | 
| Change from baseline in ESSPRI total score |  | At Week 48 | 
| Change from baseline in total stimulated salivary flow |  | At Week 48 | 
| Number of participants With Treatment Emergent Adverse Events (TEAEs) |  | Baseline (Day 1) to Week 56 | 
| Number of participants With Treatment Emergent Serious Adverse Events (TESAEs) |  | Up to Week 56 | 
| Number of participants With Adverse Events of Special Interest (AESIs) |  | Up to Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sjögren's Syndrome With Moderate-to-severe Systemic Disease Activity Study Phase: Phase 3, European Alliance of Associations for Rheumatology Sjögren's Syndrome Disease Activity Index (ESSDAI), European Alliance of Associations for Rheumatology Sjögren's Syndrome Patient Reported Index (ESSPRI), European Alliance of Associations for Rheumatology (EULAR)