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)

Bettina Hohberger; Marion Ganslmayer; Thomas Harrer; Friedrich Kruse; Stefanie Maas; Tobias Borst; Ralph Heimke-Brinck; Andreas Stog; Thomas Knauer; Eva Rühl; Victoria Zeisberg; Adam Skornia; Alexander Bartsch; Armin Ströbel; Monika Wytopil; Caroline Merkel; Sophia Hofmann; Katja G Schmidt; Petra Lakatos; Julia Schottenhamml; Martin Herrmann; Christian Mardin; Jürgen Rech

doi:10.1016/j.eclinm.2025.103358

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)

EClinicalMedicine. 2025 Jul 22:86:103358. doi: 10.1016/j.eclinm.2025.103358. eCollection 2025 Aug.

Authors

Bettina Hohberger^{1

2}, Marion Ganslmayer³, Thomas Harrer^{2

4

5}, Friedrich Kruse¹, Stefanie Maas⁶, Tobias Borst⁷, Ralph Heimke-Brinck⁷, Andreas Stog¹, Thomas Knauer¹, Eva Rühl¹, Victoria Zeisberg¹, Adam Skornia¹, Alexander Bartsch¹, Armin Ströbel⁶, Monika Wytopil^{5

8}, Caroline Merkel⁹, Sophia Hofmann¹, Katja G Schmidt^{1

4

5}, Petra Lakatos¹, Julia Schottenhamml¹, Martin Herrmann^{2

5}, Christian Mardin¹, Jürgen Rech^{2

5}

Affiliations

¹ Department of Ophthalmology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
² Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Germany.
³ Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
⁴ Infectious Diseases and Immunodeficiency Section, Department of Medicine 3, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
⁵ Department of Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
⁶ Centre for Clinical Studies (CCS), Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
⁷ Pharmacy of the University Hospital Erlangen, Uniklinikum Erlangen, Erlangen, Germany.
⁸ Institute of Clinical and Molecular Virology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.
⁹ Department of Medicine 2, Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Germany.

Abstract

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.

Keywords: Fatigue; Functional autoantibody; GPCR; GPCR-fAAb; Long-COVID; PCS subtypes; Post-COVID syndrome; Quality of life; Rovunaptabin.