US-based clinical-stage pharmaceutical company Nivalis Therapeutics has dosed the first patient in a second phase 2 clinical trial of N91115 to treat cystic fibrosis (CF).
N91115 is a stabiliser of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which has already completed a phase 1a dose-escalation safety trial in healthy volunteers, and a phase 1b safety trial in people with CF who have two copies of the F508del-CFTR mutation.
Nivalis noted that the drug works through a new mechanism of action called S-nitrosoglutathione reductase (GSNOR) inhibition, which is supposed to modulate the unstable and defective CFTR protein responsible for CF.
The GSNOR inhibition restores GSNO levels, modifying the chaperones responsible for CFTR protein degradation.
In preclinical testing, this stabilising effect was shown to increase and prolong the function of the CFTR protein and can lead to an increase in net chloride secretion.
This effect is both complementary and agnostic to other CFTR modulators such as Orkambi.
The second phase 2 clinical trial will evaluate the effect of N91115 as add-on therapy to Kalydeco (ivacaftor) in adult patients who have one copy of the F508del mutation and a second mutation that results in a gating defect in the CFTR protein.
The 12-week, double-blind, randomised, placebo-controlled, parallel group trial is designed to investigate the efficacy and safety of 400mg of N91115 administered twice daily in adult patients with CF, who are heterozygous for F508del-CFTR and a gating mutation that is approved for treatment with Kalydeco.
A total of 20 CF patients will be randomised to either N91115 with Kalydeco or placebo with Kalydeco in the multicentre trial.
The primary efficacy endpoint of the trial is the within group absolute change from baseline in per cent predicted FEV1 in the N91115 treatment group.
The trial is expected to be completed by the first half of next year.
CF is a life-shortening genetic disease that affects around 70,000 people worldwidee, mainly in the US and Europe, according to the Cystic Fibrosis Foundation.