评估 RNase 在严重疲劳与 SARS-CoV-2 感染后急性后遗症相关患者中的影响：RSLV-132 的一项随机 2 期试验。

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.

机构信息

Department of Rheumatology, University of Alabama, Birmingham, Alabama, USA.

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington, USA.

出版信息

Clin Infect Dis. 2024 Sep 26;79(3):635-642. doi: 10.1093/cid/ciae205.

DOI:10.1093/cid/ciae205

PMID:38728385

Abstract

BACKGROUND

Severe 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).

METHODS

This 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).

RESULTS

A 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.

CONCLUSION

While 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.

摘要

背景

严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的 RNA 和 RNA 碎片在感染后数周至数月内持续存在于病毒库中，可能会引发干扰素的产生和慢性炎症。RSLV-132 是一种由具有催化活性的人 RNase1 与 IgG1 Fc 融合而成的生物药物，旨在保持循环并消化细胞外 RNA。我们假设从潜伏的病毒库中清除 SARS-CoV-2 病毒 RNA 可能会改善与 SARS-CoV-2 感染后急性后遗症（PASC）相关的炎症、神经炎症和疲劳。

方法

这是一项针对 24 周 PASC 病史和严重疲劳的参与者的 2 期、双盲、安慰剂对照随机临床试验。该试验的主要终点评估了 6 次静脉注射 RSLV-132 对第 71 天基线时的变化的影响，使用患者报告的结局测量信息系统疲劳简短表单 7a（PROMIS 疲劳 SF 7a）进行评估。

结果

主要或次要终点在第 71 天没有观察到统计学上的显著差异。这可能是由于试验期间安慰剂的反应增加。通过 PROMIS 疲劳 SF 7a、慢性病治疗疲劳功能评估（FACIT-Fatigue）和医生总体评估（PGA）工具测量的疲劳得到了显著改善，并且女性对 RSLV-132 的反应大于男性，这些改善在试验早期就观察到了。