Candidate: Trans sodium crocetinate (TSC)
Type: First-in-class small molecule designed to safely re-oxygenate oxygen-deprived tissue, alone or with other treatments. TSC is Diffusion’s lead drug, and was originally developed in conjunction with the U.S. Office of Naval Research, which was seeking to treat multiple organ failure and its resulting mortality caused by low oxygen levels from blood loss in battle.
Status: Diffusion said September 10 that it dosed the first two patients in its open-label Phase Ib lead-in trial of TSC, designed to assess the drug in 24 hospitalized COVID-19 patients. The study is being conducted at the Romanian National Institute of Infectious Diseases. In addition to evaluating the safety and tolerability of TSC, the trial will collect preliminary data on TSC’s effects on arterial blood oxygenation. Diffusion expects that the data will provide proof of concept for TSC in hypoxemic patients, and can be used to guide design of a planned follow-on efficacy study.
The follow-on trial is envisioned as a randomized, placebo-controlled safety and efficacy study of TSC in hospitalized COVID-19 patients that will be conducted in the U.S. and Europe after consultation with, and approval from, local regulatory authorities, Diffusion said.
In July, Diffusion filed an IND with the FDA describing an international clinical development program in the U.S. and E.U., newly titled as Phase 1b/2b, testing TSC in a total of approximately 424 COVID-19 patients with symptoms of impaired respiratory function and low oxygen levels.
The IND details plans for three studies consisting of an open-label Phase Ib lead-in trial followed by two randomized double-blinded Phase IIb trials. The lead-in trial will be designed to assess TSC in 24 hospitalized COVID-19 patients at the Romanian National Institute of Infectious Diseases (NIID), collecting data on safety and possible increased oxygenation, thereby helping determine TSC dosing for follow-on studies.
Diffusion said it expected to begin dosing the first patient in the lead-in trial later this month, based on additional guidance from the Romanian National Agency for Medicines and Medical Devices (NAMMD) and an amendment to the company’s Clinical Trial Application, filed in June with NAMMD.
The Phase II trials are expected to be conducted in parallel—one in the U.S., the other at NIID. Each study is planned to enroll approximately 200 hospitalized COVID-19 patients to study the safety and efficacy of TSC compared to placebo. Data from the Romanian and U.S. Phase IIb trials are targeted for the first and second quarters of 2021, respectively.
TSC generated a four-fold improvement in two-year survival among newly-diagnosed, inoperable glioblastoma patients in a Phase II study, leading to a Phase III registration trial that is currently enrolling patients.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: