Download This Paper
Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.
Efficacy and Tolerability of AXA1125 (Endogenous Metabolic Modulator) in Fatigue-Predominant Long COVID: A Randomized, Double-Blind, Controlled Study
21 Pages Posted: 14 Feb 2023
More...Abstract
Background: ‘Long COVID’ describes persistent symptoms, commonly fatigue, lasting beyond 12 weeks following SARS-CoV-2 infection. Potential causes include reduced mitochondrial function and cellular bioenergetics. AXA1125 has previously increased β-oxidation and improved bioenergetics in preclinical models/certain clinical conditions, therefore may reduce fatigue associated with Long COVID. This Phase 2a pilot study aimed to assess the efficacy, safety and tolerability of AXA1125 in Long COVID.
Methods: Patients were randomized (1:1) using Interactive Response Technology in a UK based single centred double blinded, controlled study with either AXA1125 or matching placebo. Both were administered twice daily for four weeks with a two week follow-up period. Primary endpoint was the mean change in the phosphocreatine (PCr) recovery rate following moderate exercise, assessed by P-magnetic resonance spectroscopy (MRS). Trial was registered at ClinicalTrials.gov: NCT05152849; https://clinicaltrials.gov/ct2/show/NCT05152849.
Findings: Participants were recruited between December 2021-May 2022. Changes in skeletal muscle phosphocreatine recovery time PCr and 6MWT did not significantly differ between treatment (n=21) and placebo group (n=20). However, within the treatment group, patients with improved fatigue levels (n=15) demonstrated significantly greater improvements in PCr (P=0.0024) and 6MT distance (P=0.045) compared to non-responders (n=6). AXA1125 significantly reduced (from baseline to Day 28) pre-exercise CFQ-11 total fatigue score compared with placebo (least squares mean difference [LSMD] -4.30, 95% CI -7.14, -1.47; P=0.0039). Eleven (52.4%, AXA1125) and 4 (20.0%, placebo) patients reported treatment-emergent adverse events; none were serious, or led to treatment discontinuation.
Interpretation: AXA1125 may alleviate the fatigue-based symptoms in Long COVID following a four week treatment period and could be the first oral therapy. Further investigations are warranted.
Trial Registration: Trial was registered at ClinicalTrials.gov: NCT05152849; https://clinicaltrials.gov/ct2/show/NCT05152849.
Funding: Funded by Axcella Therapeutics.
Declaration of Interest: LF, MPC, HL, SN and LV have no relevant conflicts of interest to declare. MK, JP, KA, DK are employees of Axcella Therapeutics and may hold stock/options in the company. HM has received consultancy fees from Axcella Therapeutics. BR is a consultant and speaker for, and has received research support from, Axcella Therapeutics.
Ethical Approval: The study was approved by the Health Research Authory Fast Track REC (REC Reference: 21/FT/0158) and the UK Medicines and Healthcare Products Regulatory Authority (MHRA) (reference number: CTA 54043/0003/001-0001). All participants provided written informed consent prior to study entry.
Keywords: Long COVID, mitochondrial dysfunction, magnetic resonance spectroscopy, therapy
Suggested Citation: Suggested Citation