Sjogren's SyndromePhase 2RSLV-132NCT03247686
A Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome
A Phase 2 study testing RSLV-132 in people with Sjogren's Syndrome, run by Resolve Therapeutics at 2 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Sjogren's Syndrome
- What is being tested?
- RSLV-132
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 Feb 2017to 1 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
University Hospitals Birmingham
Birmingham, Edgbaston, B16 6TT
Newcastle upon Tyne Hospitals
Newcastle upon Tyne, Gosforth, NE3 3HD
About this study
Official title: A Phase 2, Double-blind, Placebo-controlled Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome
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.
Read the 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.
- Conditions
- Sjogren's Syndrome
- Being tested
- RSLV-132, Placebo
- Medical subject headings
- Sjogren's Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RSLV-132Drug
RNase Fc fusion protein
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
| RSLV-132 | Active comparator | Experimental drug Receives: Drug: RSLV-132 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 and Day 99
Secondary outcomes (1)
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).
Measured: Days 1, 29, 57, 85 and 99
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2017
- Study start1 Feb 2017
- Primary completion15 Jul 2018
- Study completion1 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sjogren's SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Resolve Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University Hospital Birmingham, Newcastle-upon-Tyne Hospitals NHS Trust
- Responsible party
- Sponsor
- Investigators
- James Posada, Ph.D., Study director, Resolve Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03247686
- Sponsor's protocol ID
- 132-04
- Acronym
- RSLV-132
- Status last verified
- Oct 2020
- First submitted
- 3 Aug 2017
- Last updated
- 2 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32798283
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-blind, Placebo-controlled Study of RSLV-132 in Subjects With Primary Sjogren's Syndrome
- ClinicalTrials.gov ID
- NCT03247686
- Acronym / sponsor ID
- RSLV-132 / 132-04
- Conditions
- Sjogren's Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Resolve TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- University Hospital Birmingham, Newcastle-upon-Tyne Hospitals NHS Trust
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 15 Jul 2018 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 14 Aug 2017 (actual)
- Results
- Posted 2 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
| RSLV-132 | Active comparator | Drug: RSLV-132Experimental drug |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RSLV-132RNase Fc fusion protein | Drug | RSLV-132 |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
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.
1 secondary outcome
EULAR ESSDAI Total Score.
Time frame: Days 1, 29, 57, 85 and 99
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32798283Posada 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Posada, Ph.D. study director
Resolve Therapeutics
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RSLV-132 in people with Sjogren's Syndrome, run by Resolve Therapeutics at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood Cell Gene Expression (time frame: Day 1 and Day 99). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03247686, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2021; AzTrials last refreshed its copy on 6 Nov 2026.