A Study to Evaluate the Efficacy and Safety of VIB4920 in Participants With Sjögren's Syndrome

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the efficacy, safety, and tolerability of VIB4920 (formerly MEDI4920) in adult participants with Sjögren's Syndrome (SS).

Detailed Description
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The study will enrol 2 SS populations: Population 1 will include participants with moderate to high systemic disease activity defined by European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) >= 5; Population 2 will include participants with moderate to severe subjective symptoms defined by EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score >= 5 and residual stimulated salivary flow but with mild systemic disease activity defined by ESSDAI score < 5. This study will include 3 periods: screening (4 weeks), treatment period (40 Weeks) and follow-up period (12 weeks). In the treatment period, participants from each of the populations will be randomized at 1:1 ratio to receive intravenous (IV) dose of VIB4920 or placebo (Stage I). After completion of Stage I, participants randomized to VIB4920 in Stage I will receive placebo and participants randomized to placebo in Stage I will receive VIB4920 (Stage II). Participants who had study drug discontinuation will not be eligible for treatment during Stage II. All participants will be followed for at least 12 weeks after their last dose of study drug administration.

Official Title
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A Phase 2 Randomized, Double-blind, Placebo-controlled, Proof of Concept Study to Evaluate the Efficacy and Safety of VIB4920 in Subjects With Sjögren's Syndrome (SS)

Conditions
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Sjögren's Syndrome

Intervention / Treatment
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* Drug: VIB4920
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with SS by meeting the 2016 American College of Rheumatology (ACR)/EULAR Classification Criteria. Residual salivary gland function as defined by whole stimulated salivary flow > 0.1 mL/min (only for Population 2). Have an ESSDAI score of >= 5 at screening; (not including the peripheral nervous system, central nervous system, and pulmonary domains) (only for Population 1). Have an ESSPRI score of >= 5 at screening (only for Population 2). Have an ESSDAI score of < 5 at screening (only for Population 2). Positive for either anti-Ro autoantibodies or rheumatoid factor, or both at screening. Male and female participants who agree to follow protocol defined contraceptive methods. No active or untreated latent tuberculosis (TB). Exclusion Criteria: Medical history of confirmed deep venous thrombosis or arterial thromboembolism within 2 years of signing the informed consent form (ICF). Risk factors for venous thromboembolism or arterial thrombosis, prothrombotic status. Concomitant polymyositis or dermatomyositis or systemic sclerosis. Active malignancy or history of malignancy, except in situ carcinoma of the cervix and cutaneous basal cell carcinoma. Hepatitis B, hepatitis C, or human immunodeficiency virus infection. More than one episode of herpes zoster and/or an opportunistic infection in the last 12 months. Active viral, bacterial, or other infections or history of more than 2 infections requiring intravenous antibiotics within 12 months prior to signing the ICF. Participants with corona virus disease 2019 (COVID-19) infection or who, in the judgment of the investigator, are at unacceptable risk of COVID-19 or its complications. A documented positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) test within 2 weeks prior to randomization. Received live (attenuated) vaccine within the 4 weeks prior to ICF signature. Treated with any biologic B-cell-depleting therapy within 12 months or other B-cell targeting therapy < 3 months before randomization. Injectable corticosteroids (including intraarticular) or treatment with > 10 mg/day dose oral prednisone or equivalent within 6 weeks prior to randomization (only for Population 1). Treated with systemic corticosteroids for indications other than SS, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) for more than a total of 2 weeks within 24 weeks prior to screening visit (only for Population 1). Received previous treatment with anti-CD40L compounds at any time before screening. Pregnant or lactating or planning to get pregnant during the duration of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: VIB4920 Dose 1 in Population 1<br>Participants in population 1 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II. | Drug: VIB4920<br>* Intravenous Dose 1.<br>* Other names: Dazodalibep;Drug: Placebo<br>* Intravenous dose matched to VIB4920.<br>|
| Placebo Comparator: Placebo in Population 1<br>Participants in population 1 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II. | Drug: VIB4920<br>* Intravenous Dose 1.<br>* Other names: Dazodalibep;Drug: Placebo<br>* Intravenous dose matched to VIB4920.<br>|
| Experimental: VIB4920 Dose 1 in Population 2<br>Participants in population 2 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II. | Drug: VIB4920<br>* Intravenous Dose 1.<br>* Other names: Dazodalibep;Drug: Placebo<br>* Intravenous dose matched to VIB4920.<br>|
| Placebo Comparator: Placebo in Population 2<br>Participants in population 2 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II. | Drug: VIB4920<br>* Intravenous Dose 1.<br>* Other names: Dazodalibep;Drug: Placebo<br>* Intravenous dose matched to VIB4920.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) at Day 169 in Population 1 |  | Baseline (Day 1) and Day 169 | 
| Change From Baseline in EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at Day 169 in Population 2 |  | Baseline (Day 1) and Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in ESSPRI at Day 169 in Population 1 |  | Baseline (Day 1) and Day 169 | 
| Percentage of Participants achieving ESSDAI [3] and ESSDAI [4] response in Population 1 |  | Baseline (Day 1) to Day 169 | 
| Percentage of Participants achieving ESSPRI response in Population 2 |  | Baseline (Day 1) to Day 169 | 
| Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Score at Day 169 in Populations 1 and 2 |  | Baseline (Day 1) and Day 169 | 
| Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169 in Populations 1 and 2 |  | Baseline (Day 1) and Day 169 | 
| Patient's Global Impression of Severity at Day 169 in Populations 1 and 2 |  | Day 169 | 
| Number of participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Populations 1 and 2 |  | From Baseline (Day 1) up to Day 365 | 
| Number of participants With Adverse Events of Special Interest (AESIs) in Populations 1 and 2 |  | From Baseline (Day 1) up to Day 365 | 
| Number of Participants With Abnormal Laboratory Parameters, Vital Signs, and Electrocardiograms (ECGs) Reported as TEAEs in Populations 1 and 2 |  | From Baseline (Day 1) up to Day 365 | 
| Plasma Concentration of VIB4920 |  | Day 1 to Day 365 | 
| Percentage of Participants With Positive Antibody Titer to VIB4920 in Populations 1 and 2 |  | Day 1 to Day 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sjögren's Syndrome, SS, VIB4920, MEDI4920