Clinical Trials

Date: 2016-12-07

Type of information: Initiation of the trial

phase: 2

Announcement: initiation of the trial

Company: Cymabay Therapeutics (USA - CA)

Product: seladelpar - MBX-8025 (2-[4-[[(2R)-2-ethoxy-3-[4-(trifluoromethyl)phenoxy]propyl]thio]-2-methylphenoxy]acetic acid (1:1) lysine dihydrate)l

Action mechanism:

• PPAR agonist. Seladelpar (MBX-8025) is a potent and selective agonist of PPARdelta, a nuclear receptor important for lipid transport, storage and metabolism in liver and muscle. The FDA has granted CymaBay orphan drug designation for seladelpar as a treatment for PBC. In addition, seladelpar has been granted the PRIority MEdicines (PRIME) Designation for the treatment of PBC by the European Medicines Agency. CymaBay has also completed a pilot Phase 2 clinical study showing that seladelpar lowers LDL-C in patients with homozygous familial hypercholesterolemia (HoFH).  The FDA has also granted CymaBay orphan drug designation for seladelpar as a treatment for HoFH and Fredrickson types I and V hyperlipoproteinemias.

 

Disease: primary biliary cholangitis

Therapeutic area: Rare diseases - Hepatic diseases - Liver diseases

Country:

Trial details:

Latest news:

• • On December 7, 2016, CymaBay Therapeutics announced the initiation of a new Phase 2 study of seladelpar in patients with primary biliary cholangitis (PBC). In this open label study, patients who have had an inadequate response to, or are intolerant to, ursodiol will be enrolled to receive seladelpar, either 5 or 10 mg, for 8 weeks. Based on the review of the 8-week data, new patients will be enrolled to receive seladelpar 25 mg for 8 weeks. The study also incorporates an extension phase where patients will be able to continue treatment for a total of 26 weeks during which it will be possible to adjust the dose of seladelpar. The primary endpoint will be the change in alkaline phosphatase (ALP), a parameter that has been used in prior clinical studies with PBC and which is believed to reflect the status of the disease. A variety of secondary outcomes will also be studied. The study is designed to enroll approximately 36 patients in the U.S., Canada, Germany and the U.K.
• An earlier Phase 2 study of seladelpar in subjects with PBC was terminated earlier this year when proof-of-concept was demonstrated by marked improvements in biochemical markers of cholestasis, including ALP. The study also identified a treatment emergent signal of transaminase elevations. The magnitude of the ALP reductions in the study suggested that lower doses may retain ALP reductions while avoiding transaminase elevations.
• • On October 5, 2016, CymaBay Therapeutics announced that after receiving input from the FDA, it has determined the next step in the development of MBX-8025 in subjects with primary biliary cholangitis (PBC).
• An initial Phase 2 study of MBX-8025 in subjects with primary biliary cholangitis was terminated earlier this year when proof-of-concept was demonstrated by marked improvements in biochemical markers of cholestasis, including alkaline phosphatase (ALP), a surrogate biomarker that has been linked to clinical outcomes in PBC. The study also identified a treatment emergent signal of transaminase elevations. The magnitude of the ALP reductions in the study suggested that lower doses may retain ALP reductions while avoiding transaminase elevations. After discussions with regulatory authorities, the company will be initiating a second Phase 2 study that will investigate lower doses of MBX-8025 in subjects with PBC to optimize the response. Initiation of the study is expected by year end 2016.

 

Is general: Yes