A novel, first-in-class oral therapy showed meaningful improvement in over half of scleroderma patients in a Phase II trial for serious inflammatory and fibrotic diseases.
In a recent Phase II study, FT011, a novel, first-in-class oral therapy for chronic fibrosis in multiple organs showed meaningful improvements in over 60 percent of scleroderma patients after 12 weeks.
FT011 is a novel biologic target in the fibrosis mechanism as a defined G protein-coupled receptor (GPCR). This GPCR is silent in healthy tissue but activated following injury or disease. Evidence demonstrates the role this GPCR has on multiple downstream pathways causing inflammation and fibrosis. FT011 inhibits this GPCR, offering potential to treat chronic fibrosis in multiple organs.
Scleroderma is an autoimmune condition characterised by inflammation and fibrosis of the skin and other organs (commonly the lungs, kidneys, and heart). Scleroderma has the highest mortality among rheumatic diseases. Patients commonly experience loss of mobility and function, pain, and fatigue.
Phase II study of FT011
The 30 patients in the chronic fibrosis study were randomly assigned to three treatment arms. One group received 400mg, the second: 200mg, or placebo daily, in addition to standard of care, for 12 weeks. Compared to placebo, both FT011 treatment groups showed clinically meaningful improvements in the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score, as early as week eight and reaching a maximum at week 12.
Compared to placebo, clinically meaningful improvements were seen in 60 percent of patients treated with FT011 400mg (p = 0.019 vs. placebo) and 20 percent of patients in the FT011 200mg group. Three patients in the pooled FT011 group achieved a maximum CRISS score of 1.0, representing the greatest probability of clinical improvement.
Other efficacy measures showed significantly improvement: skin thickness (defined by the modified Rodnan Skin Score, mRSS), lung function (percentFVC), physician-reported assessment and quality of life evaluations.
An open label extension phase of the trial is ongoing where a sub-set of patients who completed the main study (up to week 12), have elected to remain on treatment (FT011 400mg) for an additional nine months.
The study safety profile of the oral therapy demonstrated that FT011 was safe and well tolerated. It showed no differences in adverse event (AE) rates between the treatment arms. No serious AEs were reported, nor did any AEs result in study drug interruption, withdrawal, or discontinuation.
Potential for treating chronic fibrosis
Certa Therapeutics CEO and founder Professor Darren Kelly stated, “The changes seen in CRISS score, lung function, and physician reported outcomes in addition to the patient reported outcomes within such a short treatment timeframe of 12 weeks, is unprecedented and paves the way for a confirmatory global Phase III study.”
“… FT011 precisely targets the root cause of fibrosis and has the potential to offer treatment across multiple organs within these patients,” Professor Kelly concluded.
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