Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial

Maria J G T Vehreschild, Petar Atanasov, Kateryna Yurko, Cristian Oancea, Georgi Popov, Valentina Smesnoi, Gheorghe Placinta, Hella Kohlhof, Daniel Vitt, Evelyn Peelen, Jelena Mihajlović, Andreas R Muehler, Maria J G T Vehreschild, Petar Atanasov, Kateryna Yurko, Cristian Oancea, Georgi Popov, Valentina Smesnoi, Gheorghe Placinta, Hella Kohlhof, Daniel Vitt, Evelyn Peelen, Jelena Mihajlović, Andreas R Muehler

Abstract

Introduction: Vidofludimus calcium has shown anti-inflammatory effects in clinical trials of autoimmune diseases and recently demonstrated antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We performed a double-blind, randomized, placebo-controlled, phase 2 trial to evaluate the safety and efficacy of vidofludimus calcium in patients hospitalized for coronavirus disease 2019 (COVID-19) in Europe and the USA.

Methods: Patients aged 18 years or older who positive for COVID-19 were randomized (1:1) to receive placebo or 45 mg vidofludimus calcium for 14 days with both groups receiving standard-of-care treatment. The primary endpoint was the need for invasive ventilation after 28 days (ClinicalTrials.gov NCT04379271; EudraCT 2020-001264-28).

Results: Between June 12, 2020 and December 10, 2020, a total of 223 were randomized to receive either placebo (n = 112) or vidofludimus calcium (n = 111); three patients withdrew consent and were not treated. Eight (9%) patients in the placebo group and 12 (11%) patients in the vidofludimus calcium group needed invasive ventilation during the 28-day study period, which was lower than the assumed rate of 40%. Time to clinical improvement was shorter by approximately 1 day in the vidofludimus calcium group (15.0 days [90% CI 14.8-15.9]) compared to the placebo group (15.9 days [90% CI 14.9-19.9]). This effect was greatest in patients who initiated therapy within 9 days of symptom onset (3.8 days shorter in the vidofludimus calcium group). Higher trough concentrations of vidofludimus calcium were associated with quicker time to clinical recovery. The rate and timing of appearance of anti-SARS-CoV-2 antibodies were not different between groups. Serious adverse events occurred in 4 (4%) patients in the placebo group and 2 (2%) patients in the vidofludimus calcium group; treatment-emergent adverse events of increased severity related to COVID-19 occurred in 13 (12%) patients in the placebo group and 8 (7%) patients in the vidofludimus calcium group. Overall mortality was low (2%).

Conclusions: These findings support vidofludimus calcium being safe and well tolerated in patients with COVID-19.

Keywords: COVID-19; Dihydroorotate dehydrogenase inhibitor; Vidofludimus calcium.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
Time to clinical improvement in the intention-to-treat analysis (a), in patients with at least one risk factor for respiratory failure (b), and association between plasma trough vidofludimus calcium concentration at day 6 and clinical recovery (c). Risk factors were age 65 years and older, cardiovascular disease (including hypertension), pre-existing pulmonary disease, diabetes, malignancy, medical condition leading to immunodeficiency, current or recent (within 3 months) immunosuppressive treatment. Clinical improvement was defined as an at least 2-point improvement on the WHO 9-category ordinal scale (as assessed by the investigator), or live discharge from hospital without oxygen supplementation, whichever comes first. Patients in Bulgaria had a fixed hospitalization period of a minimum of 14 days as requested by their local regulatory agency. For that reason, patients in Bulgaria are not included in the assessment of clinical improvement (placebo n = 33 and vidofludimus calcium n = 37). Quartile 1, < 2.6 μg/mL; guartile 2, 2.6–4.0 μg/mL; quartile 3, 4.0–5.5 μg/mL; quartile 4, ≥ 5.5 μg/mL
Fig. 3
Fig. 3
Percentage of patients who developed IgA antibodies, IgG antibodies, and/or both at day 28. Patients are from the intention-to-treat population who provided evaluable samples at day 28

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