A Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome

Study Overview
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Brief Summary
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The present study will examine the role of circulating RNA complexed with autoantibodies and immune complexes and its role in activation of inflammatory pathways in patients with primary Sjogren's syndrome. The study will be conducted in a subset of Sjogren's patients who have elevated levels of autoantibodies and a pattern of elevated interferon-stimulated gene expression in blood cells. A number of biochemical and clinical parameters will be analyzed to determine the potential therapeutic utility of nuclease therapy in Sjogren's syndrome.

Detailed Description
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This is a multi-center, double-blind, placebo-controlled study to evaluate the impact of 8 intravenous infusions of RSLV-132 in 28 patients with primary Sjogren's syndrome. Each of the subjects will be randomized 3:1 (active:placebo) and will receive 8 infusions of 10 mg/kg of RSLV-132 or placebo as follows on days: • 1, 8, 15, 29, 43, 57, 71, and 85 Potential subjects will be screened to assess their eligibility to enter the study within 60 days prior to study entry (i.e., prior to Baseline visit). Following Baseline evaluations on Day 1, subjects will receive their first infusion of RSLV-132 or placebo. Subjects will return to the research unit for follow-up visits as described in Appendix A. Dose selection rationale: The dose level was chosen based on safety and tolerability data from Protocol 132-02 (multiple ascending dose study in SLE patients). Additionally, in a 6-month toxicology study in cynomolgus monkeys, 50 mg/kg of RSLV-132 was administered by IV infusion weekly. No dose-limiting toxicity was noted, therefore the No Observed Adverse Effect Level is at least 50 mg/kg, providing at least a 5-fold safety margin for this study. RSLV-132 shall be prepared for each subject from individual stock vials provided by Sponsor. Details of dilution, dose preparation, and administration instructions will be provided in the Study Drug Reference Guide. The dose for each individual shall be based on the subject's body weight.

Official Title
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A Phase 2, Double-blind, Placebo-controlled Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome

Conditions
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Sjogren's Syndrome

Intervention / Treatment
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* Drug: RSLV-132
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet 4 of 6 criteria of 2002 American-European Consensus Group (AECG) criteria for Primary Sjogren's Syndrome Presence of anti Ro autoantibodies Presence of interferon signature Exclusion Criteria: Use fo hydroxychloroquine within 30 days of baseline Use of cyclophosphamide within 180 days of baseline Use of oral corticosteroids greater than 10 mg/day Known IgG4-related disease

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: RSLV-132<br>Experimental drug | Drug: RSLV-132<br>* RNase Fc fusion protein<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Cell Gene Expression | Interferon gene expression (mean log2 fold change from baseline to Day 99). The of expression of three IFN-inducible genes (HERC5, EPSTI1, CMPK2) was measured by qPCR to assess the IFN signature status (the altered pattern of gene expression) of Sjögren's syndrome patients. | Day 1 and Day 99 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EULAR ESSDAI Total Score. | Clinical disease activity: Change from Baseline to Day 99 in European League Against Rheumatism Sjögren's Syndrome Disease Activity Index Total Scores (imputed values with last observation carried forward). The scale ranges from 0 to 123. A higher score means more disease activity (worse outcome). | Days 1, 29, 57, 85 and 99 |