Ground-breaking results in Phase 2 scleroderma study by Certa Therapeutics demonstrates improvement in more than 60% of patients

• Data from Certa Therapeutics' Phase 2 clinical trial with development candidate FT011 demonstrates clinically meaningful improvements for more than 60 percent of patients with scleroderma after 12 weeks of treatment;
• Clinically meaningful improvements were reported in CRISS (the key composite endpoint for systemic sclerosis) lung function, SHAQ-DI and Physician Global Assessment;
• The trial results also showed FT011 to be safe and well tolerated in this patient population;
• FT011 is a novel, first-in-class oral therapy for the treatment of chronic fibrosis in multiple organs;
• Certa's novel compounds, including FT011, target a previously undrugged GPCR receptor: these early efficacy outcomes in scleroderma offer exciting promise for treating other indications in Certa Therapeutics' pipeline, including diabetic and other forms of chronic kidney disease (CKD) and diabetic retinopathy.

MELBOURNE, Australia, Feb. 6, 2023 /PRNewswire/ -- Certa Therapeutics (Certa) today announces ground-breaking clinical trial data for FT011, its novel therapy for the treatment of serious inflammatory and fibrotic diseases.

Certa has recently completed a global Phase 2, multi-centre, randomised, double blind, placebo-controlled study of the pharmacokinetics, pharmacodynamic effects, and safety, of oral FT011 in patients with scleroderma.

Scleroderma is an extremely debilitating, potentially life-threatening autoimmune condition characterised by inflammation and fibrosis of the skin and other organs (commonly the lungs, kidneys, and heart). This condition results in high morbidity with substantial detriment on quality of life, with patients commonly experiencing loss of mobility and function, pain, fatigue, often accompanied with a significant impact to their mental health. Scleroderma has the highest mortality among rheumatic diseases.

Results of this Phase 2 study indicate that compared to placebo, treatment with FT011 led to significant improvements across multiple efficacy measures including; the American College of Rheumatology Combined Response Index in diffuse cutaneous Systemic Sclerosis (CRISS) score,1 skin thickness (defined by the modified Rodnan Skin Score, mRSS), lung function (%FVC), physician-reported assessment and quality of life evaluations. The ARC-CRISS results describe a composite measure of disease state and organ damage that predicts the probability of improvement from baseline in scleroderma patients as a range between 0.0 to 1.0, with a score of greater than 0.6 indicating a clinically meaningful improvement.

Certa's Phase 2 trial demonstrated that treatment with FT011 resulted in a clinically meaningful improvement in 60 percent of patients treated with FT011 400mg (p = 0.019 vs. placebo) and 20 percent of patients in the FT011 200mg group.2 Three patients in the pooled FT011 group achieved a maximum CRISS score of 1.0, representing the greatest probability of clinical improvement.

Certa Therapeutics CEO and founder Professor Darren Kelly says, "These exceptional trial results demonstrate the potential of this novel treatment for patients with scleroderma. 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."

"We know that this debilitating and life-threatening disease can severely impact the lives of patients and to date existing treatments only focus on the relief and management of symptoms, whereas FT011 precisely targets the root cause of fibrosis and has the potential to offer treatment across multiple organs within these patients," Professor Darren Kelly adds.

The trial recruited a total of 30 adults who were randomly assigned to 3 treatment arms: FT011 400mg or FT011 200mg or placebo daily, in addition to standard of care, for 12 weeks. When compared to placebo, both FT011 treatment groups showed clinically meaningful improvements in CRISS score as early as week 8 and reaching a maximum at week 12. 

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 400 mg) for an additional 9 months.

In addition to the outstanding CRISS score results, the breadth of clinical benefit of FT011 in scleroderma patients was also indicated through the change in modified Rodnan Skin Score (mRSS) which showed notable changes in skin thickness for patients treated with FT011 (average -3.2 for 400mg, -3.2 for 200mg and -1.9 for placebo groups respectively). Five patients in the pooled FT011 group recorded substantial changes in mRSS of -8 or greater at week 12.

For patient reported outcomes assessed using the Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI)3 over the 12 weeks, the 400 mg FT011 group showed a statistically significant improvement (p = 0.019) while the placebo group demonstrated a worsening in outcomes.  Of the health assessment components that contribute to the SHAQ-DI, the FT011 400 mg group demonstrated statistically significant improvements over 12 weeks of treatment when compared to placebo for pain, breathing problems, finger ulcers and overall disease activity.

Global physician assessments of the patients' health status showed a significant difference in favour of the 400 mg FT011 group vs. placebo at 4, 8 and 12 weeks (week 12 treatment difference of –23.36; p = 0.022).

The study safety profile demonstrated that FT011 was safe and well tolerated, with no differences in adverse event (AE) rates between the treatment arms. There were no serious AEs reported in the study, nor any AEs resulting in study drug interruption, withdrawal, or discontinuation.

Dr Wendy Stevens, a leading rheumatologist at St Vincent's Hospital Melbourne, and a Principal Investigator in the FT011 trial, says, "The trial demonstrated that FT011 was safe and well tolerated.  Scleroderma can lead to severe and life-threatening issues and patients with the condition often face daily struggles as a result of their symptoms.  These results are a significant step towards helping patients with this debilitating disease.  Further longer and larger trials of this medication are now needed to assess its potential to improve this debilitating condition."

Certa's positive Phase 2 results add to the extensive body of data regarding its lead candidate FT011. FT011 has demonstrated promising efficacy in multiple non-clinical efficacy models of fibrotic disease, with recent transcriptomic research demonstrating that treatment with FT011 results in reversal in the activation of genetic markers associated with fibrosis,4 as well as an excellent safety profile in Phase 1 studies.

Certa is developing other novel therapies focused on treating fibrotic diseases which account for 45 percent of all deaths globally in the industrialised world, demonstrating a huge unmet need. Certa's global Phase II trial in scleroderma patients provides a promising indication of FT011's potential efficacy in treating inflammation and fibrosis more generally as scleroderma affects most organs in the body.

More about the Phase 2 study

"A Phase II, randomised, double blind, placebo-controlled study of the pharmacokinetics, pharmacodynamic effects and safety of oral FT011 doses in participants with diffuse systemic sclerosis (SSc)" ClinicalTrials.gov Identifier: NCT04647890

1. The American College of Rheumatology Composite Response Index in Systemic Sclerosis (CRISS) score is a composite measure of disease state and organ damage that predicts the probability of improvement from baseline (0 - 1.0, no to high probability) in scleroderma patients.  It incorporates and evaluates a change in five core components; the modified Rodnan Skin Score (mRSS) - a measure of skin thickness, forced vital capacity (FVC), Scleroderma Health Assessment Questionnaire - Disability Index (SHAQ-DI) and global physician and patient assessments scales. A clinically meaningful improvement is defined as a CRISS score of ≥ 0.6.

D Khanna, et al., Arthritis Rheumatol. 2016; 68(2): 299–311. doi:10.1002/art.39501

2. A formal sample size calculation for efficacy endpoints was not conducted for this study.

3. SHAQ-DI assesses five scleroderma-specific visual analogue scale (VAS) items to measure the impact on a participant's daily activities; 1) intestinal disease, 2) breathing problem, 3) Raynaud syndrome, 4) finger ulcers, and 5) overall disease.

4. S Eddy, et al., "Identification of Non-Invasive Surrogates as Predictors of Response to FT011 in Kidney Disease" ASN Kidney Week 2022, abstract 3767783

FT011 is an investigational product which have not received marketing authorisation or approval by any regulatory agency, including the US Food and Drug Administration, the European Medicines Agency, or the Australian Therapeutic Goods Agency. The investigational drug products being developed by Certa Therapeutics are undergoing clinical studies to evaluate the safety and effectiveness in humans.

About Certa Therapeutics & FT011

Certa Therapeutics is a biotechnology company focused on improving lives by developing innovative precision treatments for inflammatory and fibrotic diseases.

Certa Therapeutics has designed a platform of candidate drugs and validated the role of a novel receptor which mediates signalling pathways associated with inflammation and fibrosis. These targeted drug candidates have established proof of concept as potential treatments for multiple fibrotic diseases including serious and chronic conditions impacting the kidney, lung, eye, skin, and heart. The morbidity and mortality impact of fibrotic diseases is substantial, ultimately causing 45 percent of all deaths globally.

Certa Therapeutics is seeking to combine these innovative therapeutics with biomarkers and genetic analysis to identify those patients most likely to benefit from treatment. Significant breakthroughs are urgently needed in this field, addressing a market worth more than US$15B annually.

Breakthrough research conducted by Certa Therapeutics has identified 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 is a novel drug which inhibits this GPCR, offering potential to treat chronic fibrosis in multiple organs.

https://certatherapeutics.com/

View original content:https://www.prnewswire.com/news-releases/ground-breaking-results-in-phase-2-scleroderma-study-by-certa-therapeutics-demonstrates-improvement-in-more-than-60-of-patients-301738152.html