Trial of golexanolone for PBC cognitive symptoms to resume
Study was put on hold due to technical issues with drug's production
A Phase 1b/2a clinical trial of golexanolone, Umecrine Cognition’s candidate therapy for cognitive symptoms and fatigue related to primary biliary cholangitis (PBC), will resume enrollment after a temporary hold.
Karolinska Development, which holds the majority of Umecrine shares, announced a trial delay in March, the result of technical issues producing golexanolone’s oral capsules.
In a company press release, the company announced that the trial (EudraCT2022-000422-16) will again begin recruiting adult PBC patients with clinically significant cognitive difficulties and fatigue at sites across the U.K., Germany, Italy, and Serbia. Eligible participants must not have forms of cirrhosis, or irreversible liver scarring, that pronouncedly affect liver function.
Addressing PBC’s cognitive symptoms, fatigue
In PBC, a chronic form of cholangitis, the bile ducts that carry the digestive fluid bile from the liver to the intestines become inflamed. Blocked by the inflammation, bile accumulates to toxic levels in the liver and leaks into the bloodstream. This leads to symptoms such as itchiness and jaundice, that is, yellowing of the skin and eyes.
Around half of people with PBC may also have cognitive impairment, including difficulty concentrating and with memory. Fatigue can also have a significant impact on patients’ quality of life.
The causes of PBC’s behavioral symptoms aren’t entirely understood, but those who experience cognitive and emotional symptoms tend to have higher levels of allopregnanolone, a molecule that activates GABA-A receptors on neurons. The overactivation of these receptors can cause cognitive issues and fatigue.
An oral therapy, golexanolone suppresses the interactions between allopregnanolone and GABA-A receptors. Other medications can block GABA-A, but may produce problematic side effects, like seizures or unconsciousness, but golexanolone doesn’t entirely block these receptors’ function, which Umecrine expects will minimize side effects.
In a previous Phase 2 trial (EudraCT2016-003651-30) of adults with hepatic encephalopathy, a condition wherein liver disease causes brain dysfunction, golexanolone was shown to be well tolerated and associated with cognitive improvements.
The five-day Phase 1b portion of the ongoing PBC trial found the therapy to be generally safe and well tolerated. Based on the results, the researchers identified optimal doses to use as part of the Phase 2a part, where participants will take golexanolone capsules twice daily for 28 days.
This part of the trial will continue to monitor for adverse events and serious adverse events, and will also examine the treatment’s efficacy. Specifically, researchers will assess how golexanolone affects cognitive function, fatigue, daytime sleepiness, and health-related quality of life via several validated measures.
