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)

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.

Fig. 1

Trial profile. The population included all treated participants who received at least one administration of the study drug. The population enrolled was randomised by our study pharmacy of the Universitätsklinikum Erlangen. Randomised participants passed all study inclusion or exclusion criteria. Before the infusion of either rovunaptabin (dosage: 1350 mg) or placebo PCS patients had to undergo a gargle water PCR-COVID-test in order to exclude acute SARS-CoV-2 infections. RCT: patients received either rovunaptabin/placebo on their 2nd visit with seven visits as follow-up; cross-over: patients received rovunaptabin–placebo or placebo–rovunaptabin at the 8th visit with 7 visits as follow-up. In total 14 visits were planned for each study-participant. RCT: missing visits n = 1 (rovunaptabin group); missing visits n = 0 (placebo group); cross-over: missing visits n = 2 (rovunaptabin–placebo); missing visits n = 2 (placebo–rovunaptabin); total missing visits were n = 5; for the primary variable TAE all documented TAEs were analysed regardless of drop-out or no missing visits. ¹One patient did not receive rovunaptabin due to an adverse event after placebo administration.

Fig. 2

Fatigue scores assessed at V2, V4, V5, V6, and V7. (A) FACIT scores, (B) Bell scores, and (C) FSS mean scores of study participants. Depicted are medians with IQR and ranges. Means are shown as crosses. (D) SF36 vitality scores, (E) SF36 General Health scores, (F) SF36 social functioning scores, and (G) SF36 mental component summary scores of study participants. Depicted are medians with IQR and ranges. Means are shown as crosses. Sequence A n V2–V6 = 14, n V7 = 13. Sequence B n V2–7 = 16. One patient in sequence A only received the first infusion (rovunaptabin) at V2 (ER28). One patient in sequence B only received the first infusion (placebo) at V2 (ER36).