On May 13, 2020, Immunic announced that it had received first regulatory approval from Germany’s BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte) to initiate a phase 2 clinical trial of its selective oral DHODH inhibitor, IMU-838, in coronavirus disease 2019 (COVID-19). The CALVID-1 study is a prospective, multicenter, randomized, placebo-controlled, double-blind phase 2 clinical trial in approximately 230 patients with moderate COVID-19, designed to evaluate efficacy, safety and tolerability of IMU-838. Dosing of the first patient is expected to occur later this month. Top-line data was expected to be available later the year.

Immunic recently announced that IMU-838 had successfully demonstrated preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, IMU-838 was observed to inhibit replication of clinical isolates of SARS-CoV-2 associated with COVID-19. In cellular assays, IMU-838 demonstrated this antiviral activity at concentrations which are well below the blood concentrations associated with IMU-838 dosing regimens studied in ongoing and previous clinical trials. In addition, IMU-838 has an attractive pharmacokinetic, safety and tolerability profile and, to date, has already been tested in about 650 individuals.

The aim of the CALVID-1 trial was to investigate IMU-838 as an oral treatment option for COVID-19 and to enable the use of IMU-838 as a treatment for current and potential future pandemic threats. The trial was expected to initially enroll approximately 230 patients at 10-35 centers across Europe and the United States. Patients were randomized to receive either 22.5 mg of IMU-838 twice daily, or placebo twice daily, for 14 consecutive days. All patients were also eligible to receive investigator’s choice of standard-of-care therapy throughout the duration of the study. Inclusion criteria were hospitalized adult patients with a confirmed SARS-CoV-2 infection fulfilling clinical status category 3 or 4, as assessed with the nine-category ordinal scale proposed by the World Health Organization (WHO) COVID-19 Therapeutic Trial Synopsis, as well as certain additional clinical and laboratory conditions. The primary endpoint was the proportion of patients free of invasive ventilation throughout the entire study period. Secondary endpoints included duration of hospitalization, duration of intensive care unit (ICU) treatment, 28-day all-cause mortality, time to clinical improvement and viral titer reduction.

The CALVID-1 study employed an adaptive trial strategy by including interim safety and efficacy assessments. If clinical activity of IMU-838 is confirmed by the Independent Data Monitoring Committee after the first interim analysis, which is scheduled to occur after approximately 200 patients have completed the blinded treatment period, an expansion of this trial into a confirmatory phase 3 trial could be recommended.