First healthy volunteer dosed in trial of PH lung disease treatment CS014
Bridging study expected to 'remove need' for safety testing of PH-ILD therapy
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The first participant has been dosed in a clinical trial testing the pharmacological properties of CS014, an oral therapy candidate Cereno Scientific is developing as a potential treatment for pulmonary hypertension associated with interstitial lung disease (PH-ILD).
The study, which is being run in Sweden, is testing CS014 in healthy volunteers. The results, anticipated later this year, are expected to inform plans for a future Phase 2b clinical trial testing CS014 in people with PH-ILD.
The so-called PK-bridging study was “designed based on feedback received in a … meeting with [the U.S. Food and Drug Administration (FDA)],” Cereno stated in a company press release, noting that this early trial “is expected to remove the need for additional non-clinical safety studies and a Phase [2a] trial.”
Sten R. Sörensen, Cereno’s CEO, said the trial’s launch “marks an important operational and regulatory milestone for CS014 as we continue advancing the program toward Phase [2b] development.” Generally speaking, smaller Phase 2a studies test a drug’s pharmacological properties, while usually larger Phase 2b trials may test certain doses for effectiveness.
“Dosing of the first volunteer demonstrates the strong execution capabilities of our team and partners and reflects our focused strategy to efficiently advance innovative therapies with disease-modifying potential for patients with rare cardiopulmonary diseases with high unmet medical needs,” Sörensen said.
Interstitial lung diseases, or ILDs, are a group of disorders marked by abnormal fibrosis, or scarring, in the lungs. In some patients, this can lead to pulmonary hypertension (PH), defined by elevated pressure in the vessels that carry blood from the heart through the lungs.
Early trial testing pharmacological properties of CS014
CS014 is designed to block the activity of histone deacetylases (HDACs), a group of proteins that help regulate genetic activity in cells. These proteins specifically control how DNA is physically packaged within cells, which affects which genes are turned on or off. Typically, genes that are turned on are left easily accessible, while inactivated genes are packed tightly away in the biochemical equivalent of long-term storage.
In preclinical tests, blocking HDACs has been shown to influence biological processes, such as tissue scarring and blood vessel abnormalities, that help drive PH-ILD.
The main goal of the new clinical trial is to assess CS014’s pharmacokinetic or PK profile, meaning how the therapy is absorbed into, moves through, and is excreted from the body. The study will compare CS014’s profile with that of valproic acid, a well-studied HDAC inhibitor that is used to prevent seizures. Participants will receive either CS014 or valproic acid for one week, then will switch to the other drug for another week.
The study … [aims] to significantly shorten the clinical development timeline and reduce development costs for CS014.
The pharmacokinetic study was designed following discussions with the FDA and is expected to eliminate the need for additional safety and pharmacological studies before launching a Phase 2b study. Phase 2b clinical trials are generally medium-sized studies that aim to provide proof of concept for whether an experimental therapy is safe and effective for treating a disease. The results of such trials typically lay the groundwork for larger Phase 3 trials to definitively test effectiveness.
“The study is intended to provide important comparative pharmacokinetic data and aim to significantly shorten the clinical development timeline and reduce development costs for CS014,” said Rahul Agrawal, chief medical officer and head of research and development at Cereno.
In addition to PH-ILD, Cereno is advancing CS014 as a potential treatment for a specific type of ILD called idiopathic pulmonary fibrosis. The company is also developing another HDAC inhibitor called CS1, which is a reformulation of valproic acid, as a potential treatment for PH.
CS1 has shown promise in early clinical testing in people with pulmonary arterial hypertension, and an expanded access program demonstrated a positive safety profile after one year of treatment, according to the developer.
