Clinical trial investigating potential investigational treatment for relief of fatigue in people with long COVID reports results
14 April 2023
Researchers from the University of Oxford have reported findings from a Phase 2 clinical trial investigating the efficacy of an investigational treatment against long COVID fatigue.
The study (reported in Lancet eClinical Medicine) found participants given the treatment, developed by US pharmaceutical company Axcella Therapeutics, reported feeling less fatigued than those given a placebo.
This is one of the first randomized double-blind placebo controlled trials of a potential long COVID treatment – AXA1125. Randomised control trials are considered to be gold standard for testing potential treatments for an illness.
People living with long COVID in the trial who received AXA1125 had a significant improvement in fatigue compared to those who received a placebo (material matched in appearance and taste to the investigational treatment). The study was double-blind, that is, neither the patients nor the researchers working with the patients knew which patients had the treatment and which patients had a placebo.
AXA1125 was tested in long COVID fatigue as previous data from Axcella showed effects on cellular energetics and inflammation. Emerging data on long COVID suggests that the virus targets the mitochondrial, which are essential to normal energy generation and control of inflammation. AXA1125 may improve energy generation and reduce the amount of inflammation in the body.
Of the 41 patients taking part in this study, half had the investigational treatment (an orange-flavoured powder dissolved in water) twice daily for four weeks, while the other half had a placebo. On average, patients had symptoms of fatigue for about 18 months prior to entering the study. All the patients who started the study completed it, and none reported serious adverse effects of either the treatment or the placebo.
The research team also tracked mitochondrial health in the patients’ muscles before and after they took the medication, using state-of-the-art magnetic resonance spectroscopy scans of the patients’ calf muscles as they bent and straightened their leg against the mild resistance from an exercise band.
The scans showed no overall difference between the patients who took the treatment versus the placebo. Although there was no overall difference in mitochondrial health between patients who received the treatment versus those who were administered a placebo, those in the treatment arm did report significantly improved fatigue levels. Those who reported an improvement in fatigue also had improved mitochondrial health and walked further compared to those without.
Principal Investigator, Associate Professor Betty Raman from the Radcliffe Department of Medicine at Oxford University, said:
‘The reduction in patients’ own reports of fatigue is really positive news, and we hope that further work will help us understand the underlying processes behind this improvement too.
‘There is still some way to go in treating all patients with long COVID – our results focus specifically on fatigue, rather than the breathlessness and cardiovascular issues that other long COVID patients have reported.
‘We also selected patients who had clear signs of mitochondrial function being disturbed – effects of the medication on other symptoms remains to be evaluated in future studies.’
The research team also hope that future studies determine if the treatment is effective for an even larger group of long COVID patients.
Study author Margaret Koziel MD, Axcella Chief Medical Officer, said:
‘We are encouraged by these results, and hope that a treatment for people who suffer from long COVID fatigue may be in sight.
‘We are energized to advance AXA1125 further towards being made available to the millions of patients currently without treatment options. Our approach allows us to target several pathways that are disrupted in long COVID, and our previous experience with AXA1125 suggests that is both easy to take and well tolerated in clinical studies.’
By the end of last year, over 500 million cases of COVID-19 were reported across the world. Of these, up to 10% are thought to be suffering from Long COVID. Fatigue is one of the main symptoms experienced by patients and there is as yet no approved treatment for the condition.
The study was funded by Axcella Therapeutics.
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About the Radcliffe Department of Medicine
The Radcliffe Department of Medicine is one of the two main departments of medicine at the University of Oxford, and aims to tackle some of the world’s biggest health challenges by integrating innovative basic biology with cutting edge clinical research. RDM has internationally renowned programmes in a range of areas including cardiovascular sciences, diabetes and endocrinology, immunology, haematology and pathology. https://www.rdm.ox.ac.uk/
About the University of Oxford
Oxford University has been placed number 1 in the Times Higher Education World University Rankings for the seventh year running, and number 2 in the QS World Rankings 2022. At the heart of this success are the twin-pillars of our ground-breaking research and innovation and our distinctive educational offer.
Oxford is world-famous for research and teaching excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research alongside our personalised approach to teaching sparks imaginative and inventive insights and solutions.
Through its research commercialisation arm, Oxford University Innovation, Oxford is the highest university patent filer in the UK and is ranked first in the UK for university spinouts, having created more than 200 new companies since 1988. Over a third of these companies have been created in the past three years. The university is a catalyst for prosperity in Oxfordshire and the United Kingdom, contributing £15.7 billion to the UK economy in 2018/19, and supports more than 28,000 full time jobs.
About Axcella Therapeutics (Nasdaq: AXLA)
Axcella is a clinical-stage biotechnology company pioneering a new approach to treat complex diseases using compositions of endogenous metabolic modulators (EMMs). The Company’s product candidates are comprised of EMMs and derivatives that are engineered in distinct combinations and ratios to reset multiple biological pathways, improve cellular energetics, and restore homeostasis. Axcella’s pipeline includes lead therapeutic candidates for the treatment of Long COVID and non-alcoholic steatohepatitis (NASH). The Company’s unique model allows for the evaluation of its EMM compositions through non-IND clinical studies or IND clinical trials. For more information, please visit www.axcellatx.com.
AXA1125 is a proprietary multi-targeted EMM composition consisting of five amino acids and an amino acid derivative that works via multiple biological pathways. Preclinical and clinical data have shown this oral product candidate’s potential to increase fatty acid oxidation, ATP production, ketogenesis and mitochondrial bioenergetics, contributing to meaningful reductions in key markets of liver fat, insulin resistance, inflammation and fibrosis. AXA1125 was also investigated in the EMMPACT Phase 2b clinical trial in nonalcoholic steatohepatitis (NASH) as well as the Phase 2a clinical trial in Long COVID reported here. AXA1125 is not approved for use as a treatment and is investigational.