罗武那他宾（也称为BC007）对新冠后综合征患者疲劳及生活质量的安全性、耐受性和临床效果（reCOVer）：一项前瞻性、探索性、安慰剂对照、双盲、随机IIa期临床试验（RCT）
Safety, tolerability and clinical effects of rovunaptabin, also known as BC007 on fatigue and quality of life in patients with Post-COVID syndrome (reCOVer): a prospective, exploratory, placebo-controlled, double-blind, randomised phase IIa clinical trial (RCT).
作者信息
Hohberger Bettina, Ganslmayer Marion, Harrer Thomas, Kruse Friedrich, Maas Stefanie, Borst Tobias, Heimke-Brinck Ralph, Stog Andreas, Knauer Thomas, Rühl Eva, Zeisberg Victoria, Skornia Adam, Bartsch Alexander, Ströbel Armin, Wytopil Monika, Merkel Caroline, Hofmann Sophia, Schmidt Katja G, Lakatos Petra, Schottenhamml Julia, Herrmann Martin, Mardin Christian, Rech Jürgen
机构信息
Department of Ophthalmology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Germany.
出版信息
EClinicalMedicine. 2025 Jul 22;86:103358. doi: 10.1016/j.eclinm.2025.103358. eCollection 2025 Aug.
BACKGROUND
Rovunaptabin neutralises functional autoantibodies targeting G-Protein coupled receptors (GPCR-fAAbs), observed in patients with Post-COVID syndrome. As we hypothesise an improvement of PCS by rovunaptabin, the aim of reCOVer was to investigate safety, tolerability, and clinical effects of rovunaptabin in PCS patients.
METHODS
reCOVer is a prospective, exploratory, placebo-controlled, double-blind, randomised phase IIa clinical investigator initiated trial with 1350 mg rovunaptabin with additional cross-over at the Universitätsklinikum Erlangen, Germany. The trial was registered in EudraCT, 2022-001781-35. Screening was done between 21·11·2023 and 25·06·2024. Eligible participants (18-80 years) showed GPCR-fAAbs, at least 3/8 defined PCS symptoms persisting ≥3 months after COVID-19 and fatigue as major symptom. Participants were randomly assigned (1:1) to either receive rovunaptabin or placebo at day 0 (d0) and d48 with a follow-up of 28 days, respectively. Primary endpoint was the number of treatment emergent adverse events (TEAE) at d28 (co-primary endpoint: TEAE at d70); secondary endpoint focused on fatigue and quality of life.
FINDINGS
Thirty PCS patients were randomised and analysed. RCT analysis showed nine (rovunaptabin) and five TEAEs (placebo), yet without statistically significance (p = 0·1299; CI -14·80%; 63·02%); one serious adverse event, not related to treatment, was recorded. Rovunaptabin showed a neutralisation of GPCR-fAAb and a significant improvement of FACIT Fatigue Scale (effect size = 2·10, p = 0·0378), Bell score (effect size = 3·64, p = 0·0004), Fatigue Severity Scale (effect size = -2·66, p = 0·0088), and quality of life (4/8 items).
INTERPRETATION
As this proof-of-concept study showed effects on the patient-centred endpoint PCS and a good safety profil, subsequent studies are needed to confirm these results in a larger cohort.
FUNDING
German Federal Ministry of Education and Research, German Research Foundation.
背景
罗武纳他滨可中和新冠后综合征患者体内靶向G蛋白偶联受体的功能性自身抗体（GPCR-fAAbs）。鉴于我们推测罗武纳他滨可改善新冠后综合征，“reCOVer”研究的目的是调查罗武纳他滨在新冠后综合征患者中的安全性、耐受性和临床效果。
方法
“reCOVer”是一项前瞻性、探索性、安慰剂对照、双盲、随机的IIa期临床研究，由研究者发起，在德国埃尔朗根大学医院使用1350毫克罗武纳他滨，并进行了额外的交叉试验。该试验已在欧盟临床试验数据库（EudraCT）注册，注册号为2022-001781-35。筛查在2023年11月21日至2024年6月25日期间进行。符合条件的参与者（18至80岁）体内存在GPCR-fAAbs，在新冠感染后至少有3/8种定义的新冠后综合征症状持续≥3个月，且以疲劳为主要症状。参与者在第0天（d0）和第48天被随机分配（1:1）接受罗武纳他滨或安慰剂治疗，随访28天。主要终点是第28天出现的治疗中出现的不良事件（TEAE）数量（共同主要终点：第70天的TEAE）；次要终点侧重于疲劳和生活质量。
研究结果
30名新冠后综合征患者被随机分组并进行分析。随机对照试验分析显示，罗武纳他滨组有9例（罗武纳他滨）和安慰剂组有5例出现TEAE，但无统计学意义（p = 0.1299；CI -14.80%；63.02%）；记录到1例与治疗无关的严重不良事件。罗武纳他滨显示出对GPCR-fAAb的中和作用，并且在FACIT疲劳量表（效应大小 = 2.10，p = 0.0378）、贝尔评分（效应大小 = 3.64，p = 0.0004）、疲劳严重程度量表（效应大小 = -2.66，p = 0.0088）和生活质量（8项中的4项）方面有显著改善。
解读
由于这项概念验证研究显示了对以患者为中心的新冠后综合征终点有影响且安全性良好，因此需要后续研究在更大的队列中证实这些结果。
资助
德国联邦教育与研究部、德国研究基金会。
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