Nivalis Therapeutics has announced that a clinical study of its investigational drug N91115 for cystic fibrosis has begun treating its first patient.
N91115 works through a novel mechanism, called S-nitrosoglutathione reductase (GSNOR) inhibition. This mechanism is thought to modulate the unstable and defective CFTR protein that causes CF. GSNOR inhibition restores GSNO levels, thus changing the chaperones responsible for CFTR protein degradation. In preclinical trials, the stabilizing effect was seen to increase and prolong CFTR protein function, and could augment net chloride secretion. This effect is both complementary and agnostic to other CFTR modulators, like Orkambi.
The 12-week trial is a double-blind, randomized, placebo-controlled, parallel group study, planned to evaluate the efficacy and safety of two doses of N91115, 200mg and 400mg, administered twice a day to 135 adult CF patients homozygous for the F508del-CFTR mutation and currently being treated with Orkambi.
The primary efficacy outcome is the absolute change from baseline in percent predicted in forced expiratory volume in 1 second (FEV1). Secondary outcomes include changes in the sweat chloride, the CFQ-R Respiratory Symptom scale and Body Mass Index (BMI). More information, including conditions for possible enrollment, are available on the study’s webpage. Results are expected in July 2016.