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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

See all articles by Lucy Elizabeth Mary Finnigan

Lucy Elizabeth Mary Finnigan

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR)

Mark Philip Cassar

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR)

Margaret James Koziel

Axcella Therapeutics

Joel Pradines

Axcella Therapeutics

Hanan Lamlum

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR)

Karim Azer

Axcella Therapeutics

Dan Kirby

Axcella Therapeutics

Hugh Montgomery

University College London - Division of Medicine

Stefan Neubauer

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR)

Ladislav Valkovič

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR)

Betty Raman

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR)

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

Finnigan, Lucy Elizabeth Mary and Cassar, Mark Philip and Koziel, Margaret James and Pradines, Joel and Lamlum, Hanan and Azer, Karim and Kirby, Dan and Montgomery, Hugh and Neubauer, Stefan and Valkovič, Ladislav and Raman, Betty, Efficacy and Tolerability of AXA1125 (Endogenous Metabolic Modulator) in Fatigue-Predominant Long COVID: A Randomized, Double-Blind, Controlled Study. Available at SSRN: https://ssrn.com/abstract=4356755 or http://dx.doi.org/10.2139/ssrn.4356755

Lucy Elizabeth Mary Finnigan

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR) ( email )

Mark Philip Cassar

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR) ( email )

Margaret James Koziel

Axcella Therapeutics ( email )

Joel Pradines

Axcella Therapeutics ( email )

Hanan Lamlum

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR) ( email )

Karim Azer

Axcella Therapeutics ( email )

Dan Kirby

Axcella Therapeutics ( email )

Hugh Montgomery

University College London - Division of Medicine ( email )

Stefan Neubauer

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR) ( email )

Ladislav Valkovič

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR) ( email )

Betty Raman (Contact Author)

University of Oxford - Oxford Centre for Clinical Magnetic Resonance Research (OCMR)

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