A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Impact of Intravenous RSLV-132 in Participants with Primary Sjögren's Syndrome (pSS) with Moderate to Severe Symptom Burden

The goal of this clinical study is to learn if RSLV-132 improves the symptoms of pSS in adults. It will also learn about the safety of RSLV-132. The main questions it aims to answer are:
* Does RSLV-132 improve the cardinal symptoms of Sjogren's including fatigue, dryness and pain?
* Does RSLV-132 improve the tiredness/fatigue caused by Sjogren's?
* What are the blood levels of RSLV-132 over time?
* What is the immune (antibody) response in the body to RSLV-132?
* What is the safety profile of RSLV-132?
Researchers will compare RSLV-132 to a placebo (a look-alike substance that contains no drug) to see if RSLV-132 improves the symptoms of pSS.
Participants will:
Take RSLV-132 or a placebo 13 times over 22 weeks Visit the clinic once every week for the first 2 weeks, then every 2 weeks until the end of treatment and then for a final time 4 weeks later (Day 211) for check-ups, tests and to answer questionnaires about their symptoms Record their symptoms every day on an electronic device

Start Date01 Sep 2024

Sponsor / Collaborator

Resolve Therapeutics LLC

NCT04944121 / CompletedPhase 2

A Phase 2, Double-blind, Placebo-controlled Study of RSLV-132 in Subjects With Post-acute COVID-19 (Long COVID)

The purpose of this study is to assess the efficacy (decrease in profound fatigue), safety and pharmacokinetics of RSLV-132 in subjects with long Corona Virus (COVID) syndome

Start Date25 Jun 2021

Sponsor / Collaborator

Resolve Therapeutics LLC

NCT03247686 / CompletedPhase 2

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.

Start Date01 Feb 2017

Sponsor / Collaborator

Resolve Therapeutics LLC

[+2]

100 Clinical Results associated with RSLV-132

100 Translational Medicine associated with RSLV-132

100 Patents (Medical) associated with RSLV-132

Literatures (Medical) associated with RSLV-132

26 Sep 2024·Clinical Infectious Diseases

Assessment of the Impact of RNase in Patients With Severe Fatigue Related to Post-Acute Sequelae of SARS-CoV-2 Infection: A Randomized Phase 2 Trial of RSLV-132

Article

Author: Krusinska, Eva ; Andrews, James S ; Boonyaratanakornkit, Jim B ; Posada, James A ; Allen, Suzanne

AbstractBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and RNA debris persist in viral reservoirs for weeks to months following infection, potentially triggering interferon production and chronic inflammation. RSLV-132 is a biologic drug composed of catalytically active human RNase1 fused to human IgG1 Fc and is designed to remain in circulation and digest extracellular RNA. We hypothesized that removal of SARS-CoV-2 viral RNA from latent reservoirs may improve inflammation, neuroinflammation, and fatigue associated with post-acute sequelae of SARS-CoV-2 infection (PASC).MethodsThis was a phase 2, double-blind, placebo-controlled randomized clinical trial in participants with a 24-week history of PASC and severe fatigue. The primary endpoint of the trial assessed the impact of 6 intravenous doses of RSLV-132 on the mean change from baseline at day 71 in the Patient-Reported Outcomes Measurement Information System Fatigue Short Form 7a (PROMIS Fatigue SF 7a).ResultsA statistically significant difference on day 71 was not observed with respect to the primary or secondary endpoints. This was likely due to a placebo response that increased during the trial. Statistically significant improvement in fatigue as measured by the PROMIS Fatigue SF 7a, Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue), and Physicians Global Assessment (PGA) instruments were observed earlier in the trial, with women demonstrating greater responses to RSLV-132 than men.ConclusionWhile fatigue was not statistically significantly improved at Day 71, earlier timepoints revealed statistically significant improvement in fatigue and physician global assessment. The data suggest eliminating latent viral RNA by increasing serum RNase activity may improve fatigue in PASC patients. Women may respond better to this approach than men. Future studies will aim to confirm these findings.

01 Feb 2024·Lupus Science & Medicine

Evaluation of RNase therapy in systemic lupus erythematosus: a randomised phase 2a clinical trial of RSLV-132

Article

Author: Burge, Daniel J ; Boackle, Susan A ; Werth, Victoria P ; Posada, James

BackgroundCirculating, extracellular RNA is the primary trigger of type I interferon in systemic lupus erythematosus (SLE), and interferon is known to play a central pathogenic role in the disease. RSLV-132 is a catalytically active human RNase molecule fused to human IgG1 Fc designed to digest RNA and thereby decrease the chronic inflammation associated with SLE. The drug was evaluated in a cohort of patients with SLE with moderate-severe cutaneous disease activity and the presence of RNA immune complexes. The primary objective of the study was the assessment of the impact of 13 doses of 10 mg/kg RSLV-132 over 6 months on the mean Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score.MethodsSixty-five patients meeting the entry criteria of a baseline CLASI score of 10 or greater and positivity of at least one of five autoantibodies to RNA-binding proteins (SM/RNP, SSA/Ro, SSB/La, Sm, RNP) were randomly assigned (2:1) to receive 13 doses of RSLV-132 10 mg/kg or placebo, respectively. Participants received study drug for 24 weeks on days 1, 8, 15, 29, 43, 57, 71, 85, 99, 113, 127, 141 and 155 with an end-of-treatment visit on day 169 and a follow-up visit at the end of the study on day 215. The primary objective was assessed on days 85 and 169. Secondary objectives included assessment of systemic disease activity using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the British Isles Lupus Assessment Group 2004 Index and the Physician’s Global Assessment. Data from these instruments were used to calculate the SLE Responder Index 4 (SRI-4) and the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) scores.ResultsThe mean CLASI score change from baseline at day 169 was −5.7 (±7.0) in the placebo group and −6.2 (±8.5) in the RSLV-132 group. A subgroup of participants with moderate-severe systemic disease activity and high baseline SLEDAI scores (≥9) were analysed with respect to BICLA and SRI-4 responses. The RSLV-132 treated participants in the high SLEDAI subgroup had a greater percentage of BICLA responses (62% vs 44%) and SRI-4 responses (23% vs 11%) as compared with placebo. A second subgroup of participants with high baseline CLASI scores (≥21) were analysed with respect to BICLA and SRI-4 responses. The RSLV-132 treated participants in the high CLASI subgroup had a greater percentage of BICLA responses (28% vs 8%) and SRI-4 responses (39% vs 8%) as compared with placebo.ConclusionsSix months of RSLV-132 therapy consisting of a weekly loading dose of RSLV-132 for 1 month, followed by 5 months of biweekly administrations did not significantly improve the mean CLASI score relative to placebo in this cohort of patients with SLE. The study entry criteria selected patients with moderate-severe cutaneous disease activity and no minimum SLEDAI score, which resulted in a wide range of systemic disease activity from inactive to severe as measured by SLEDAI. When the participants with higher SLEDAI and CLASI scores were analysed, a trend towards clinical improvement favouring RSLV-132 was observed. The results warrant further evaluation of RSLV-132 in SLE and suggest that patients with more active systemic disease are most likely to benefit from RNase therapy.

01 Jan 2021·Arthritis & RheumatologyQ1 · MEDICINE

Improvement of Severe Fatigue Following Nuclease Therapy in Patients With Primary Sjögren’s Syndrome: A Randomized Clinical Trial

Q1 · MEDICINE

Article

Author: Wilson, Douglas ; Posada, James ; Barone, Francesca ; Valadkhan, Saba ; Casement, John ; Burge, Daniel ; Gallagher, Peter ; Tarn, Jessica ; Ng, Wan‐Fai ; Fisher, Benjamin A. ; Davies, Kristen ; Jobling, Kerry

ObjectiveTo assess the safety and efficacy of RSLV‐132, an RNase Fc fusion protein, in a phase II randomized, double‐blind, placebo‐controlled clinical trial in patients with primary Sjögren’s syndrome (SS).MethodsThirty patients with primary SS were randomized to receive treatment with RSLV‐132 or placebo intravenously once per week for 2 weeks, and then every 2 weeks for 12 weeks. Eight patients received placebo and 20 patients received RSLV‐132 at a dose of 10 mg/kg. Clinical efficacy measures included the European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease Activity Index, EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐F), Profile of Fatigue (ProF), and the Digit Symbol Substitution Test (DSST).ResultsPatients randomized to receive RSLV‐132 experienced clinically meaningful improvements in the ESSPRI score (P = 0.27), FACIT‐F score (P = 0.05), ProF score (P = 0.07), and DSST (P = 0.02) from baseline to day 99, whereas patients who received placebo showed no changes in any of these clinical efficacy measures. This improvement was significantly correlated with increased expression of selected interferon‐inducible genes (Pearson’s correlations, each P < 0.05).ConclusionAdministration of RSLV‐132 improved severe fatigue, as determined by 4 independent patient‐reported measures of fatigue, in patients with primary SS.

News (Medical) associated with RSLV-132

13 May 2024

·www.prnewswire.com

Resolve Therapeutics Publishes Results of RSLV-132 Phase 2 Long COVID Study

MIAMI, May 13, 2024 /PRNewswire/ -- Resolve Therapeutics, a mid-stage clinical development company pioneering transformative therapies for autoimmune and post-viral illnesses, today announced the publication of its phase 2 long COVID results in Clinical Infectious Diseases. The publication entitled "Assessment of the Impact of RNase in Patients with Severe Fatigue Related to Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): A randomized phase 2 trial of RSLV-132" evaluated the impact of RNase in one hundred and eight patients diagnosed with COVID-19 at least 6 months prior to baseline and with a history of continuous, severe fatigue. Participants received 6 doses of RSLV-132 or placebo over two months. The study measured fatigue and overall disease activity using the PROMIS SF 10a, FACIT-Fatigue, and physician's global assessment. Approximately 18 million Americans suffer the debilitating effects of long COVID. The most common symptoms are extreme fatigue, brain fog, immune dysregulation and depression or anxiety. Despite the large unmet medical need, A recent editorial in The Lancet identified only 12 pharmacological interventional clinical trials in development. Thus, very little progress has been made towards identifying drugs to treat the cardinal symptoms of long COVID. RSLV-132 has demonstrated significant clinical activity in improving autoimmune-related fatigue in Sjogren's syndrome. Results from the current long COVID phase 2 study suggest patients suffering from long COVID may also benefit from the removal of circulating RNA. "We are encouraged by the potential for RSLV-132 to improve the debilitating fatigue suffered by so many long COVID patients" commented Dr. James Posada chief executive officer of Resolve Therapeutics. "Interestingly, our data further suggests that women may respond better to RSLV-132 and digestion of latent viral RNA than men" added Dr. Posada. About RSLV-132 RSLV-132 is a non-immunosuppressive, biologic drug comprised of catalytically active human RNase1 fused to the Fc region of human IgG1. It is designed to remain in serum circulation and digest extracellular pathogenic RNA. RNA is the primary trigger of interferon and cytokine production that drives chronic inflammation in diseases such as SLE, Sjogren's. Recent studies suggest that RNA may play a role in post-viral illnesses such as PASC and ME/CFS as well. Therefore, removing it from circulation may decrease inflammation and improve the symptoms associated with these diseases. About Resolve Therapeutics Resolve is a private biotech company pioneering a transformative approach to autoimmune and post-viral diseases. The company is leveraging the extensive body of scientific discoveries that demonstrate the central role of pathogenic RNA molecules, weather self-derived or from viral sources, in driving inflammatory and neuroinflammatory symptoms. Resolve is actively developing RSLV-132 in mid-stage clinical development programs including SLE, Sjogren's syndrome, and post-acute sequelae of SARS-CoV-2 infection (PASC). For more information please visit: Contact: James Posada Resolve Therapeutics 208-727-7010 [email protected] SOURCE Resolve Therapeutics, LLC

Phase 2Clinical ResultsiRNA

12 Feb 2024

·www.prnewswire.com

Resolve Therapeutics Announces Publication of Lupus Clinical Trial Results

MIAMI, Feb. 12, 2024 /PRNewswire/ -- Resolve Therapeutics, a mid-stage clinical development biotechnology company pioneering first-in-class therapies for autoimmune diseases, today announced the publication of results from its phase 2a clinical trial of RSLV-132 in patients with Systemic Lupus Erythematosus (SLE) in Lupus Science & Medicine. The publication entitled "Evaluation of RNase therapy in systemic lupus erythematosus: a randomized phase 2a clinical trial of RSLV-132" describes a proof-of-concept study in SLE patients with moderate-severe cutaneous disease activity. The findings suggest that patients with Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k) scores above nine respond preferentially to digestion of extracellular RNA as compared to patients with lower SLEDAI-2k scores less than nine. "We would like to express our deepest gratitude to the patients that participated in the study" commented Dr. James Posada chief executive officer of Resolve Therapeutics. "Mounting evidence substantiates the importance of extracellular RNA as a drug target in autoimmune diseases such as SLE and Sjogren's. Our study demonstrates the potential benefit of digesting circulating pathogenic RNA in selected SLE patients with active systemic disease and circulating RNA-containing autoantibodies" added Dr. Posada. About RSLV-132 RSLV-132 is a non-immunosuppressive, biologic drug comprised of catalytically active human RNase1 fused to the Fc region of human IgG1. It is designed to remain in serum circulation and digest extracellular pathogenic RNA in patients with autoimmune diseases. RNA is the primary trigger of interferon production and drives chronic inflammation in autoimmune diseases such as SLE and Sjogren's, therefore removing it from circulation may decrease inflammation and improve the symptoms associated with these autoimmune diseases. About Resolve Therapeutics Resolve is a private biotech company pioneering a completely new approach to autoimmune disease. The company is leveraging the extensive body of scientific discoveries that demonstrate the central role of pathogenic RNA molecules in autoimmune disease. Resolve is actively developing RSLV-132 in mid-stage clinical development programs icluding SLE, Sjogren's syndrome, and post-acute sequelae of SARS-CoV-2 infection (PASC). For more information please visit: Contact: James Posada Resolve Therapeutics 208-727-7010 [email protected] SOURCE Resolve Therapeutics, LLC

Phase 2Clinical ResultsiRNA

09 Nov 2022

·www.prnewswire.com

Resolve Therapeutics Completes Enrollment of Phase 2 Long Covid Clinical Trial

ST. PETERSBURG, Fla., Nov. 9, 2022 /PRNewswire/ -- Resolve Therapeutics, pioneering first-in-class, targeted, safe therapies for underserved autoimmune diseases, today announced that its phase 2 clinical trial of RSLV-132 in patients with long covid has been fully enrolled (NCT04944121). The randomized, double-blind, placebo-controlled study in patients with long covid who are suffering from debilitating fatigue has enrolled 113 participants into the study. The primary endpoint of the study will analyze an improvement in patient fatigue using the PROMIS SF 7a instrument. The last participant will complete the study in January and top-line data will be released in the first quarter of 2023. "We wish to extend our sincere thanks to the participants of the study. The knowledge gained through your participation will hopefully lead to a treatment for the tens of millions of patients suffering from long covid." Commented Dr. James Posada chief executive officer of Resolve Therapeutics. About RSLV-132 RSLV-132 is a safe, novel, targeted biologic drug designed to remove pro-inflammatory nucleic acids from the circulation of patients, which is one of the key triggers of multiple pro-inflammatory cascades. The compound consists of a catalytically active human RNase moiety fused to a human IgG1 Fc domain which digests RNA circulating in the blood and thereby decreases inflammation. About Resolve Therapeutics Resolve Therapeutics is pioneering safe, targeted therapies for underserved autoimmune diseases with large unmet medical need. The Company's lead compound, RSLV-132, a first-in-class investigational treatment in development for lupus and Sjogren's syndrome. The drug eliminates the inflammatory material found in the blood of patients with autoimmune diseases, thereby preventing the activation of numerous pro-inflammatory cascades. RSLV-132 removes just the inflammatory stimulating molecules, without shutting down the immune system or interfering with key steps in the innate immune system. For more information, visit . Contacts: James Posada Resolve Therapeutics 208-727-7010 [email protected] SOURCE Resolve Therapeutics, LLC

First in Class

100 Deals associated with RSLV-132

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Post Acute COVID 19 Syndrome	Phase 2	US	Resolve Therapeutics LLC	25 Jun 2021
Primary Sjögren's syndrome	Phase 2	GB	Resolve Therapeutics LLC	01 Feb 2017
Systemic Lupus Erythematosus	Phase 2	US	Resolve Therapeutics LLC	03 Jan 2016
Subarachnoid Hemorrhage	Preclinical	US	Resolve Therapeutics LLC	01 Nov 2024

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03247686 (RSLV-132, CTgov)	Phase 2	Primary Sjögren's syndrome	28	Placebo (Placebo)	yqfvjgobbr(hecauuaevr) = dwpwmfqqdp stklxkcvjj (zqytisbpkr, hmlviozgye - muqrynisjj) View more	-	02 Apr 2021
				RSLV-132 (RSLV-132)	gtsjdtjcel(mxhqylziqz) = vygrpofpku lfovxsffqw (fmdsyyewvl, pcwtxclsnt - xfrqskhddx) View more
NCT02660944 (CTgov)	Phase 2	Systemic Lupus Erythematosus	64	RSLV-132 (RSLV-132)	egerlwgbvf(mdwnbpomjq) = rbaaalzjdf glwxtldxst (hwllmipqtk, qrxjzjzxii - vwdlwceyzk) View more	-	10 Mar 2021
				Placebo (Placebo)	egerlwgbvf(mdwnbpomjq) = cetgkucawk glwxtldxst (hwllmipqtk, dtxncpyudu - xwmbiyxyph) View more
NCT03247686 (Pubmed \| Arthritis Rheumatol) Manual	Phase 2	Fatigue \| Primary Sjögren's syndrome	28	RSLV-132	(cicggdkrrf): P-Value = 0.02 View more	Positive	01 Jan 2021
				Placebo

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