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

• 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: Resolve Therapeutics
• Collaborators: University Hospital Birmingham; Newcastle-upon-Tyne Hospitals NHS Trust
• Information provided by (Responsible Party): Resolve Therapeutics

Tracking Information

• First Submitted Date: August 3, 2017
• First Posted Date: August 14, 2017
• Results First Submitted Date: December 1, 2020
• Results First Posted Date: April 2, 2021
• Last Update Posted Date: April 2, 2021
• Actual Study Start Date: February 1, 2017
• Actual Primary Completion Date: July 15, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 9, 2021)

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.

Original Primary Outcome Measures (submitted: August 10, 2017)

blood cell gene expression [ Time Frame: Day 99 ]

Interferon gene expression

Current Secondary Outcome Measures (submitted: March 9, 2021)

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).

Original Secondary Outcome Measures (submitted: August 10, 2017)

European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI). [ Time Frame: Day 99 ]

clinical disease activity

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Sjogren's Syndrome

Intervention

• Drug: RSLV-132
  RNase Fc fusion protein
• Drug: Placebo
  Placebo

Study Arms

• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo
• Active Comparator: RSLV-132
  Experimental drug
  Intervention: Drug: RSLV-132

• Publications *: Posada J, Valadkhan S, Burge D, Davies K, Tarn J, Casement J, Jobling K, Gallagher P, Wilson D, Barone F, Fisher BA, Ng WF. Improvement of Severe Fatigue Following Nuclease Therapy in Patients With Primary Sjogren's Syndrome: A Randomized Clinical Trial. Arthritis Rheumatol. 2021 Jan;73(1):143-150. doi: 10.1002/art.41489. Epub 2020 Nov 22.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 10, 2017): 28
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 1, 2019
• Actual Primary Completion Date: July 15, 2018 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03247686
• Other Study ID Numbers: 132-04
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Resolve Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Resolve Therapeutics
• Original Study Sponsor: Same as current

Collaborators

• University Hospital Birmingham
• Newcastle-upon-Tyne Hospitals NHS Trust

Investigators

• Study Director: James Posada, Ph.D.; Resolve Therapeutics

• PRS Account: Resolve Therapeutics
• Verification Date: October 2020