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

35 Pages Posted: 13 Apr 2022

See all articles by Maria Vehreschild

Maria Vehreschild

Universitätsklinikum Frankfurt am Main - Infektiologie

Petar Atanasov

affiliation not provided to SSRN

Kateryna Yurko

Kharkiv National Medical University

Cristian Oancea

affiliation not provided to SSRN

Georgi Popov

affiliation not provided to SSRN

Valentina Smesnoi

affiliation not provided to SSRN

Gheorghe Placinta

affiliation not provided to SSRN

Hella Kohlhof

affiliation not provided to SSRN

Daniel Vitt

affiliation not provided to SSRN

Evelyn Peelen

affiliation not provided to SSRN

Jelena Mihajlović

affiliation not provided to SSRN

Andreas R. Muehler

affiliation not provided to SSRN

Abstract

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-19 (COVID-19) in Europe and the United States. Patients aged ≥18 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). Between June 12 2020 to December 10 2020, 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 one 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 was not different between groups. Serious adverse events occurred in 4 (4%) patients in the placebo 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 placebo and 8 (7%) patients in the vidofludimus calcium group. Overall mortality was low (2%).  These findings support vidofludimus calcium is safe and well-tolerated in patients with COVID-19.

Note:
Funding Information: This work was supported by Immunic AG who funded the study.

Conflict of Interests: MJGTV: has received research grants from 3M, Astellas Pharma, Biontech, DaVolterra, Merck/MSD, Seres Therapeutics, Takeda Pharmaceutical. She has received speaker or consulting fees from Alb Fils Kliniken GmbH, Arderypharm, Astellas Pharma, Basilea, Bio-Mérieux, DaVolterra, Farmak International Holding GmbH, Ferring, Gilead Sciences, Immunic AG, Merck/MSD, Pfizer, Roche, SocraTec R&D GmbH. HK: is an employee of Immunic AG and owns shares and stock-options of the parent company of Immunic AG. DV: is an employee of Immunic AG and owns shares and stock-options of the parent company of Immunic AG. EP: is an employee of Immunic AG and owns shares and stock-options of the parent company of Immunic AG. JM: is an employee of Immunic AG and owns shares and stock-options of the parent company of Immunic AG. ARM: is an employee of Immunic AG and owns shares and stock-options of the parent company of Immunic AG and a holder of patents for the drug under investigation. All other authors have no disclosures.

Ethical Approval: Trial conduct was consistent with all applicable regulatory authorities and international regulations including International Council for Harmonisation (ICH), Guideline for Good Clinical Practice (GCP) and the Declaration of Helsinki (1996) in addition to applicable local laws and regulations. The study protocol and amendments were reviewed by institutional review boards/independent ethics committees. An IDMC safeguarded the interests of trial participants and provided recommendations on trial conduct, sample size, and safety. The IDMC also fulfilled the role of the Data Safety Monitoring Board. All participants provided written consent prior to the conduct of any trial-related procedures

Trial Registration: The study is registered with ClinicalTrials.gov (NCT04379271) and EudraCT (2020-001264-28).

Keywords: COVID-19, dihydroorotate dehydrogenase inhibitor, vidofludimus

Suggested Citation

Vehreschild, Maria and Atanasov, Petar and Yurko, Kateryna and Oancea, Cristian and Popov, Georgi and Smesnoi, Valentina and Placinta, Gheorghe and Kohlhof, Hella and Vitt, Daniel and Peelen, Evelyn and Mihajlović, Jelena and Muehler, Andreas R., Safety and Efficacy of Vidofludimus Calcium in Patients Hospitalized with COVID-19: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial. Available at SSRN: https://ssrn.com/abstract=4082907 or http://dx.doi.org/10.2139/ssrn.4082907

Maria Vehreschild (Contact Author)

Universitätsklinikum Frankfurt am Main - Infektiologie ( email )

Petar Atanasov

affiliation not provided to SSRN ( email )

No Address Available

Kateryna Yurko

Kharkiv National Medical University ( email )

4 Nauki Prospect
Kharkiv, 61022
Ukraine

Cristian Oancea

affiliation not provided to SSRN ( email )

No Address Available

Georgi Popov

affiliation not provided to SSRN ( email )

No Address Available

Valentina Smesnoi

affiliation not provided to SSRN ( email )

No Address Available

Gheorghe Placinta

affiliation not provided to SSRN ( email )

No Address Available

Hella Kohlhof

affiliation not provided to SSRN ( email )

No Address Available

Daniel Vitt

affiliation not provided to SSRN ( email )

No Address Available

Evelyn Peelen

affiliation not provided to SSRN ( email )

No Address Available

Jelena Mihajlović

affiliation not provided to SSRN ( email )

No Address Available

Andreas R. Muehler

affiliation not provided to SSRN ( email )

No Address Available

Do you have negative results from your research you’d like to share?

Paper statistics

Downloads
31
Abstract Views
210
PlumX Metrics