Ultragenyx Pharmaceutical has dosed the first participant in a Phase I/II study of its investigational messenger RNA (mRNA) therapy, UX053, to treat Glycogen Storage Disease Type III (GSDIII).
Providing the deficient protein in GSDIII patients, the therapy encodes the glycogen debranching enzyme, which is enclosed in a lipid nanoparticle.
The two-part clinical study will assess the efficacy, safety, and tolerability of the therapy in adult GSDIII patients aged 18 and above.
The first part will be an open-label study, which will enrol up to ten subjects who will be given a single-ascending UX053 dose through intravenous infusion.
Part two will be a randomised, double-blind, placebo-controlled study, which will enrol up to 16 participants across four cohorts.
In this study, the subjects will be randomised in a 3:1 ratio to receive UX053 or a placebo. It will assess five repeat doses at escalating dose levels.
Ultragenyx Pharmaceutical chief medical officer Camille Bedrosian said: “Initiation of this trial paves the way for UX053 to potentially become the first medicine for people living with GSDIII, who currently are burdened with managing a complex metabolic disorder with diet alone.
“We believe mRNA is a promising treatment modality for rare diseases like GSDIII because this technology can deliver large genes to targeted cells and achieve a high uniformity of protein expression.
“We can also individualise mRNA therapies based on the needs of each patient by adjusting the dose level and dose frequency.”
Treatment-emergent adverse events (TEAEs), related TEAEs and serious TEAEs in the two parts of the study will be the primary goals.
Meanwhile, pharmacokinetic parameters will be the trial’s secondary endpoints.
Some of the exploratory goals of the study include muscle strength, blood sugar, biomarkers of the liver, cardiac and muscle health, as well as clinician-reported and patient-reported outcomes.
Furthermore, UX053 received Orphan Drug Designation from the US Food and Drug Administration (FDA) and the European Commission to treat GSDIII.
This June, the company and GeneTx Biotherapeutics received approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) of the UK to start Phase I/II clinical study of GTX-102 for treating Angelman syndrome in children.