A Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 as Addition to Investigator's Choice of Standard of Care Therapy, in Patients With Coronavirus Disease 19 (COVID-19)

The trial consists of a Phase 2 proof-of-concept phase (Part 1) with the option to extend enrollment (without interruption) to Phase 3 (Expansion Phase, Part 2).

This trial is a multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to evaluate the safety and efficacy of IMU-838 as addition to investigator's choice of SoC treatment in patients with COVID-19. Eligible patients will be centrally randomized 1:1 to twice-daily (BID) oral 22.5 mg IMU-838 (45 mg/day + SoC) or placebo (+ SoC). Randomization will be stratified by age (\< or \>=65 years) and antiviral therapy (no antivirals, Hydroxychloroquine and Chloroquine, all other antivirals).

Adaptive sequential trial design and overall trial design

The trial uses an adaptive sequential design. An IDMC will review unblinded data and provide the Sponsor with recommendations regarding modifications of sample size and trial conduct.

A 1st interim analysis (IA1) will be performed after approximately 200 patients have completed the trial (either as scheduled or prematurely), while enrollment continues. If no activity of IMU 838 is observed by the IDMC in this IA, further patient enrollment will be stopped, and a final analysis of Part 1 will be performed (FA1). It is expected that the final analysis of Part 1 will include approximately 230 patients. If the IA1 results indicate activity of IMU-838 in COVID-19, the trial may be extended to Part 2 with a revised sample size derived by the IDMC based on IA1 results and with possible other trial adjustments. If the trial is extended into Part 2, a 2nd IA (IA2) is planned after approximately two-thirds of patients (based on the overall global sample size \[Part 1 and Part 2 combined\]) have been enrolled to potentially adjust sample size and other trial features if needed. The final analysis of the trial (FA2) will then be done after all patients have completed Part 2.

In addition, an early interim safety analysis will be performed and evaluated by the IDMC after 30 patients have been enrolled to assess unblinded safety data. Further safety analyses can be initiated at any time by the IDMC or Sponsor when new safety signals are identified within this or other trials of IMU-838.

Screening

Patients can be screened for a maximum of 2 days (from Day -2 to Day 0) and eligible patients will be randomized on Day 0 and treated with IMP + SoC for 14 days. It is encouraged to screen potential participants immediately at the day of hospitalization (including informed consent, assessment of inclusion/exclusion criteria, screening laboratory tests all done locally, assessment of clinical and blood gas criteria) and randomize patients on the same day (Day 0). To assess eligibility criteria, existing local laboratory values obtained within 48 hours of randomization can also be used, except for testing of positive status of SARS-CoV-2 infection where a 4-day window is allowed.