Nivalis Therapeutics announced the dosing of a first patient in a Phase 2 clinical trial evaluating the efficacy and safety of its investigational drug N91115, in combination with ivacaftor (Kalydeco), in people with cystic fibrosis (CF).
CF is a life-shortening genetic disease, characterized by mutations in the CFTR gene that lead to defective chloride transport by the CFTR chloride channel. Nivalis’ N91115 is designed to decrease the degradation of the defective CFTR, increasing its function. The drug’s effects are achieved through inhibition of S-nitrosoglutathione reductase (GSNOR), which ultimately modifies the chaperones responsible for CFTR protein degradation.
Preclinical studies demonstrated that N91115 is able to increase the function of CFTR bearing a mutation found in about 86 percent of CF patients, the F508del-CFTR mutation. An earlier Phase 1b study evaluated the drug’s safety in people with two copies of F508del-CFTR.
The randomized, placebo-controlled, 12-week Phase 2 trial (NCT02724527) will investigate the efficacy and safety of a 400 mg dose of N91115 in patients with one copy of F508del-CFTR and an additional gating mutation, a mutation that impairs the correct opening and closing of the CFTR channel pore, for which Kalydeco has been approved. It is being conducted at 10 U.S. sites, and currently recruiting eligible patients.
Trial investigators will randomize about 20 CF patients into either a treatment group, who will be given N91115 twice a day, or a placebo group, with both taking Kalydeco. The study’s primary endpoint will be based on absolute changes in lung function, assessed through forced expired volume after 1 second of blowing out (FEV1). The trial is expected to finish in early 2017.
“The initiation of our second Phase 2 study sets us on the path to demonstrate that a multi-mechanism approach that includes N91115 as a novel stabilizer of the CFTR protein may help CF patients already being treated with Kalydeco achieve better clinical outcomes,” Jon Congleton, president and chief executive officer of Nivalis, said in a press release. “We hope to observe a positive impact of N91115 on lung function in this trial, and add to the important research targeted at increasing treatment options that address F508del, the most common mutation of the CFTR gene. We look forward to the results of this study in the first half of 2017.”