Q&A: Phase 2 trial will assess AXA1665’s ability to reduce overt hepatic encephalopathy
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Axcella announced initiating patient screening for the EMMPOWER phase 2 clinical trials of AXA1665 for reduction in risk for recurrent overt hepatic encephalopathy, according to a press release.
AXA1665 is a multi-targeted oral product.
According to the release, researchers will randomly assign 150 patients taking lactulose with or without rifaximin, who have experienced at least one prior overt hepatic encephalopathy event and have neurocognitive dysfunction at screening to AXA1665 53.8 g daily or a calorie-matched placebo in three divided doses for 24 weeks. There will be a 4-week follow-up period for safety.
The proportion of patients with a 2-point increase or more in the psychometric hepatic encephalopathy score (PHES) after the 24-week treatment period will serve as the primary endpoint. Other endpoints include the proportion of patients experiencing an overt hepatic encephalopathy breakthrough event and time to first overt hepatic encephalopathy breakthrough event, including time to hospitalization, changes in physical function including the liver frailty index, and patient-reported outcomes. In addition, investigators will assess measures of circulating ammonia, amino acid profile and inflammation-related markers.
Healio Gastroenterology spoke with Alison Schecter, MD, president of research and development at Axcella on the study design and what they expect from phase 2 results compared with previous trials.
Healio: What is the purpose and design of the study?
Schecter: EMMPOWER is a phase 2 trial that will investigate AXA1665’s ability to improve neurocognition, reduce the recurrence of overt hepatic encephalopathy and improve muscle function and other outcomes in patients with cirrhosis. As many of your readers know, these patients may suffer from neurocognitive impairment and muscle wasting and need medical innovation. Based on the data generated and the dose ranging we have completed in the past, we have been able to design this very streamlined phase 2 trial that compares one dose of AXA1665 vs. placebo over a 24-week treatment period. Approximately 150 patients who have a history of overt hepatic encephalopathy will be enrolled across more than 70 sites globally.
Healio: What were some of the key take-aways from phase 1 trials?
Schecter: We have completed two prior non-investigational new drug clinical studies of AXA1665 in people with cirrhosis. In the largest and most recent study that was completed in 2020, AXA1665 was observed to be well tolerated with a strong safety profile. Dose-dependent improvement was noted in amino acid metabolism and across all three of the neurocognitive tests that were used over 12 weeks in 60 participants with mild and moderate hepatic insufficiency. These included improvement in the psychometric hepatic encephalopathy score (PHES) in the AXA1665 high dose arm vs. Placebo (P < .05). PHES is considered the gold standard for diagnosing minimal hepatic encephalopathy. Additionally, clinically relevant trends were seen in certain measures of nitrogen/ammonia handling and physical function in the AXA1665 arms vs. placebo.
Healio: What do you hope to find with phase 2 results?
Schecter: AXA1665 is a multi-targeted product candidate that holds the potential to address the needs of patients with overt hepatic encephalopathy more comprehensively than today’s ammonia-focused standards of care. In EMMPOWER, we hope to see a statistically significant improvement in the PHES score, which would indicate better cognitive function in patients. Additionally, we will be seeking to estimate the rate at which AXA1665 may be able to reduce overt hepatic encephalopathy events and improve patient-reported outcomes over a 6-month period.
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