Inotrem SA announced the U.S. FDA has cleared an Investigational New Drug (IND) application for the phase IIb ASTONISH trial, evaluating nangibotide (LR12), its lead compound for septic shock. The IND is now effective, allowing Inotrem to conduct the study in septic shock patients in the US.
The FDA decision was based on the review of the information provided on previous preclinical and clinical experience with nangibotide. A Phase IIa clinical study demonstrated the safety and tolerability of nangibotide in patients suffering from septic shock. Preclinical models reviewed by the FDA showed that nangibotide was able to restore appropriate inflammatory response, vascular function, and improved survival in septic shock animal models.
ASTONISH (The Efficacy, Safety and Tolerability of nangibotide in Patients with Septic Shock) is a randomized, double-blind, placebo controlled, dose selection study that will be conducted in Europe and the U.S. Four hundred and fifty patients are planned to be included in this study in 48 clinical sites. The study will compare the effect of nangibotide at two different doses versus standard of care.
The design of the ASTONISH clinical trial was discussed with the FDA during a pre-IND meeting. The regulatory process for clinical trial authorization in European countries is currently ongoing.
About Septic Shock
Septic shock is a possible consequence of bacteremia, or bacteria in the bloodstream. Bacterial toxins, and the immune system response to them, cause a dramatic drop in blood pressure, preventing the delivery of blood to the organs. Septic shock can lead to multiple organ failure, including respiratory failure and may cause rapid death. There is currently no specific therapy approved for this indication besides antibiotics and symptomatic treatment.
Nangibotide is the formulation of the active ingredient LR12, which is a 12 amino-acid peptide prepared by chemical synthesis. LR12 is a specific TREM-1 inhibitor, acting as a decoy receptor and interfering in the binding of TREM-1 and its ligand. The TREM-1 pathway is an amplification loop of the immune response that triggers an exuberant and hyperactivated immune state, which is known to play a crucial role in the pathophysiology of septic shock and acute myocardial infarction.