US-based Nivalis Therapeutics has begun a Phase II clinical trial of its lead investigational drug, N91115, a stabiliser of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein.

N91115 is currently being evaluated to treat patients with CF who have two copies of the F508del mutation when added to Orkambi (lumacaftor / ivacaftor).

The 12-week parallel group trial will evaluate the efficacy and safety of two doses of N91115, 200mg and 400mg. These will be administered twice daily in 135 adult CF patients, who are homozygous for the F508del-CFTR mutation, and being treated with Orkambi.

Nivalis president and chief executive officer Jon Congleton said: "We expect to report results from the study in the second half of next year.

"N91115 has a novel mechanism of action that stabilises the CFTR protein."

"N91115 has a novel mechanism of action that stabilises the CFTR protein, and we are optimistic about its potential ability to improve lung function in people with CF."

N91115 works through a new mechanism of action called S-nitrosoglutathione reductase (GSNOR) inhibition, which works by restoring GSNO levels, and modifying chaperones responsible for CFTR protein degradation.

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GSNOR inhibition is expected to modulate the unstable and defective CFTR protein responsible for CF.

University of North Carolina medicine associate professor and principal investigator of the study Scott Donaldson said: "Based on preclinical and Phase Ib data, we are encouraged that a therapeutic approach, including N91115 as a stabiliser of the CFTR protein, may help improve clinical outcomes.

"Importantly, N91115 has the potential to become part of a new multi-mechanism approach to treating CF."

In preclinical testing, the stabilising effect was shown to prolong the function of the CFTR protein, and may lead to an increase in net chloride secretion.

The trial’s primary outcome will be change from baseline in percent-predicted FEV1. Secondary outcomes will include changes in sweat chloride, the CFQ-R respiratory symptom scale, and body mass index (BMI).