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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