Axcella Therapeutics is in discussions with the UK Medicines and Healthcare products Regulatory Agency (MHRA) to run a registrational trial of AXA1125 in long Covid-19, CEO Bill Hinshaw says. The biotech plans to initiate regulatory conversations with the US Food and Drug Administration (FDA) in the “near term”, he tells Clinical Trials Arena.
Axcella intends to run the forthcoming registrational trial in the UK and the US, with the potential to expand further, Hinshaw notes. The trial will target patients with long Covid who are experiencing moderate-to-serious fatigue, he adds.
Earlier this morning, Axcella announced results for a 41-patient Phase IIa trial of AXA1125 in long Covid (NCT05152849). The trial did not meet its primary endpoint of phosphocreatine (PCr) recovery rate following moderate exercise, but it achieved secondary endpoints measuring mental and physical fatigue. The company’s trading volume increased by a little more than 13 times compared to yesterday, before market close.
Long Covid describes the constellation of symptoms—ranging from fatigue to breathing difficulties–that can occur over a month after an acute Covid-19 infection. There is no approved treatment, and ongoing long Covid trials have thus far had limited success.
AXA1125, which is also in a Phase II nonalcoholic steatohepatitis (NASH) trial, is a mixture of amino acids that can combat fatigue by restoring mitochondrial function.
Registrational trial endpoints
In the previous Phase IIa study, Axcella chose PCr recovery rate as a primary endpoint to assess mitochondrial function as a possible biomarker for fatigue, CMO Margaret Koziel explains. However, the upcoming trial will focus on clinically meaningful outcomes of fatigue based on positive results along these measures in the Phase IIa study, she notes.
As a primary endpoint, the forthcoming AXA1125 trial will likely use a patient-reported outcome (PRO) measure assessing fatigue, Koziel says. The Phase IIa trial reported statistically significant improvements on the Chalder Fatigue Questionnaire (CFQ-11), a patient-reported assessment of fatigue commonly used in chronic fatigue syndrome.
In addition, the upcoming study will likely include an endpoint measuring physical function, Koziel adds. The Phase IIa trial assessed physical function using a secondary endpoint of the 6 Minute Walk Test (6MWT), which measures the distance a person can walk in six minutes.
However, the registrational trial will not necessarily use the 6MWT, instead potentially using an outcome that holistically assesses a patient’s daily fatigue, Koziel explains. For instance, Axcella could consider monitoring activity digitally, using an endpoint such as change in average activity over seven-day periods, she notes.
Because there are no standardised long Covid outcome measures, Axcella will rely on ongoing regulatory conversations to finalize its exact endpoint choices, Hinshaw says. “We believe we can start up the trial quickly once we have regulatory feedback, implement [the feedback], and recruit rapidly given the high unmet need and interest in long Covid,” he says.