The January 25 version of this article was updated on July 27 to include new trials and data readouts.
Long Covid-19 can leave patients with a wide array of lingering cognitive, respiratory, and functional symptoms months after a SARS-CoV-2 infection. But researchers still do not fully understand the condition’s range of underlying causes, challenging the clinical trial design process.
Nevertheless, at least three major drug trials have readouts expected in the next year. Axcella’s AXA1125 and 9 Meters’ AT1011 expect study results in the second half of 2022. Virios’s IMC-2 has an anticipated readout in the first half of 2023.
Long Covid-19 can leave patients with a wide array of lingering cognitive, respiratory, and functional symptoms months after a SARS-CoV-2 infection. But researchers still do not fully understand the condition’s range of underlying causes, challenging the clinical trial design process.
Nevertheless, at least three major drug trials have readouts expected in the next year. Axcella’s AXA1125 and 9 Meters’ AT1011 expect study results in the second half of 2022. Virios’s IMC-2 has an anticipated readout in the first half of 2023.
Each trial has a different primary endpoint, highlighting the heterogeneity, and overall uncertainty, of long Covid. With as many as one in five people experiencing the condition following an acute infection—including many who cannot return to regular daily activities—the need for treatments looms large.
Mixed success in long Covid clinical trial
Clinical trial success in long Covid has been a mixed bag thus far. On June 15, PureTechannounced LYT-100 failed a Phase II trial targeting long Covid respiratory complications.
However, on July 29, AIM ImmunoTech reported positive Phase III results for Ampligen among a small group of patients in an expanded access program. Originally designed for patients with chronic fatigue syndrome, the study (NCT00215813) expanded to include patients with long Covid. As per the results, four patients with long Covid reported a statistically significant improvement in chronic fatigue symptoms.
Nevertheless, the long Covid field still has a long way to go before successfully developing an FDA-approved treatment. To move forward in long Covid drug development, trial endpoints “absolutely need to be standardised,” Dr Anthony Fauci, the highest ranking US medical official, told Clinical Trials Arena in June. The field must find common symptom denominators based on a deeper understanding of long Covid’s underlying pathogenesis, Fauci said.
Large-scale observational studies, like the US National Institute of Health’s (NIH) flagship RECOVERY trial (NCT05292274), are designed to learn more about long Covid’s root causes. The following three drug readouts could also shed light on the future of long Covid drug development.
Axcella takes aim at post-Covid fatigue
Axcella Health expects topline Phase IIa results in the third quarter of 2022 for its trial of AXZ1125 targeting fatigue-predominant long Covid. The 40-patient trial (NCT05152849) is recruiting subjects who have had a documented case of Covid-19 at least 12 weeks prior to screening and have exertional fatigue unexplainable by other causes.
As a primary endpoint, the placebo-controlled trial measures a four-week change in the phosphocreatine (PCr) recovery rate following moderate exercise. PCr recovery rate is a measure of mitochondrial function, which has previously been an endpoint in other conditions such as primary pulmonary hypertension where fatigue is a major symptom. Key secondary endpoints include the six-minute walk test, fatigue scores, and safety and tolerability.
AXA1125 is a mixture of amino acids that can increase fatty acid oxidation, ATP production, ketogenesis, and mitochondrial bioenergetics — leading to improved muscle function. In addition, Axcella is studying AXA1125 in the Phase IIb EMMPACT trial (NCT04880187) in nonalcoholic steatohepatitis (NASH).
Mass Gen studies long Covid in children
The Massachusetts General Hospital is investigating 9 Meters Biopharma’s AT1001 (larazotide acetate) for multisystem inflammatory syndrome in children (MIS-C) related to Covid-19. MIS-C symptoms appear an average of four weeks after a Covid-19 infection, and the condition can lead to serious inflammation that damages organs. Results for the Phase IIa trial (NCT05022303) are expected to read out in the second half of 2022.
The 20-participant, placebo-controlled study is evaluating the efficacy and safety of AT1001 on “mitigating symptoms of MIS-C” over 24 weeks, though the trial page does not specify by what measure. AT1001 reduces autoimmune responses by binding to the zonulin receptor.
Bateman Horne Center investigates long Covid symptoms
Bateman Horne Center is running a Phase IIa trial of Virios Therapeutics’ IMC-2, a combination of valacyclovir plus celecoxib, for long Covid symptoms. The open-label study is on pace to complete enrolment by the end of 2022, and topline results are expected in the first half of 2023.
The planned 14-week trial, which does not currently have a ClinicalTrials.gov listing, will enrol up to sixty patients, split equally between standard of care and IMC-2 treatment. Though the primary endpoint has not been disclosed, Virios announced that long COVID symptoms explored could include fatigue, sleep, attention, pain, autonomic function, and anxiety. Originally developed for herpes, IMC-2 can inhibit viral activation and replication.
Update: A day after publication of this article, AIM reported data from its Phase III Ampligen study. The trial results calendar and the related portions have been updated to reflect the latest information.
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