Maria J G T Vehreschild1, Petar Atanasov2, Kateryna Yurko3, Cristian Oancea4, Georgi Popov5, Valentina Smesnoi6, Gheorghe Placinta7, Hella Kohlhof8, Daniel Vitt8, Evelyn Peelen8, Jelena Mihajlović8, Andreas R Muehler8. 1. Department of Internal Medicine, Infectious Diseases, Medizinische Klinik II, University Hospital Frankfurt, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany. maria.vehreschild@kgu.de. 2. Clinic of Internal Diseases, UMHATEM "N.I.Pirogov" EAD, 21 Gen. Totleben Blvd., 1606, Sofia, Bulgaria. 3. Infectious Diseases, Kharkiv National Medical University, 4 Nauki Avenue, Kharkiv, 61022, Ukraine. 4. University of Medicine and Pharmacy "Victor Babeş" Timişoara, Gh. Adam Street No 13, 300173, Timişoara, Romania. 5. Clinic of Infectious Disease, Military Medical Academy-Sofia, 3, "St. Georgi Sofiiski" Str., 1606, Sofia, Bulgaria. 6. PMSI Clinical Hospital of Infectious Diseases "Toma Ciorba", Section 3, Bulevardul Ştefan Cel Mare şi Sfânt, Nr 163, 2004, Chişinău, Moldova. 7. PMSI Clinical Hospital of Infectious Diseases "Toma Ciorba", Section 4, Bulevardul Ştefan Cel Mare şi Sfânt, nr 163, 2004, Chişinău, Moldova. 8. Immunic AG, Lochhamer Schlag 21, 82166, Gräfelfing, Germany.
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.
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.
Authors: Christian Confavreux; Paul O'Connor; Giancarlo Comi; Mark S Freedman; Aaron E Miller; Tomas P Olsson; Jerry S Wolinsky; Teresa Bagulho; Jean-Luc Delhay; Deborah Dukovic; Philippe Truffinet; Ludwig Kappos Journal: Lancet Neurol Date: 2014-01-23 Impact factor: 44.182
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Authors: Angélica Jayk Bernal; Monica M Gomes da Silva; Dany B Musungaie; Evgeniy Kovalchuk; Antonio Gonzalez; Virginia Delos Reyes; Alejandro Martín-Quirós; Yoseph Caraco; Angela Williams-Diaz; Michelle L Brown; Jiejun Du; Alison Pedley; Christopher Assaid; Julie Strizki; Jay A Grobler; Hala H Shamsuddin; Robert Tipping; Hong Wan; Amanda Paschke; Joan R Butterton; Matthew G Johnson; Carisa De Anda Journal: N Engl J Med Date: 2021-12-16 Impact factor: 91.245