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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03247686
Recruitment Status : Completed
First Posted : August 14, 2017
Results First Posted : April 2, 2021
Last Update Posted : April 2, 2021
Sponsor:
Collaborators:
University Hospital Birmingham
Newcastle-upon-Tyne Hospitals NHS Trust
Information provided by (Responsible Party):
Resolve Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Sjogren's Syndrome Drug: RSLV-132 Drug: Placebo Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Double-blind, Placebo-controlled Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : July 15, 2018
Actual Study Completion Date : August 1, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo

Active Comparator: RSLV-132
Experimental drug
Drug: RSLV-132
RNase Fc fusion protein




Primary Outcome Measures :
  1. Blood Cell Gene Expression [ Time Frame: Day 1 and Day 99 ]
    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.


Secondary Outcome Measures :
  1. EULAR ESSDAI Total Score. [ Time Frame: Days 1, 29, 57, 85 and 99 ]
    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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Meet 4 of 6 criteria of 2002 American-European Consensus Group (AECG) criteria for Primary Sjogren's Syndrome
  2. Presence of anti Ro autoantibodies
  3. Presence of interferon signature

Exclusion Criteria:

  1. Use fo hydroxychloroquine within 30 days of baseline
  2. Use of cyclophosphamide within 180 days of baseline
  3. Use of oral corticosteroids greater than 10 mg/day
  4. Known IgG4-related disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03247686


Locations
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United Kingdom
University Hospitals Birmingham
Birmingham, Edgbaston, United Kingdom, B16 6TT
Newcastle upon Tyne Hospitals
Newcastle upon Tyne, Gosforth, United Kingdom, NE3 3HD
Sponsors and Collaborators
Resolve Therapeutics
University Hospital Birmingham
Newcastle-upon-Tyne Hospitals NHS Trust
Investigators
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Study Director: James Posada, Ph.D. Resolve Therapeutics
  Study Documents (Full-Text)

Documents provided by Resolve Therapeutics:
Study Protocol  [PDF] April 19, 2017
Statistical Analysis Plan  [PDF] July 18, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Resolve Therapeutics
ClinicalTrials.gov Identifier: NCT03247686    
Other Study ID Numbers: 132-04
First Posted: August 14, 2017    Key Record Dates
Results First Posted: April 2, 2021
Last Update Posted: April 2, 2021
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Sjogren's Syndrome
Syndrome
Disease
Pathologic Processes
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases