Interim analyses of a first-in-human phase 1/2 mRNA trial for propionic acidaemia.
Nature
; 628(8009): 872-877, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38570682
ABSTRACT
Propionic acidaemia is a rare disorder caused by defects in the propionyl-coenzyme A carboxylase α or ß (PCCA or PCCB) subunits that leads to an accumulation of toxic metabolites and to recurrent, life-threatening metabolic decompensation events. Here we report interim analyses of a first-in-human, phase 1/2, open-label, dose-optimization study and an extension study evaluating the safety and efficacy of mRNA-3927, a dual mRNA therapy encoding PCCA and PCCB. As of 31 May 2023, 16 participants were enrolled across 5 dose cohorts. Twelve of the 16 participants completed the dose-optimization study and enrolled in the extension study. A total of 346 intravenous doses of mRNA-3927 were administered over a total of 15.69 person-years of treatment. No dose-limiting toxicities occurred. Treatment-emergent adverse events were reported in 15 out of the 16 (93.8%) participants. Preliminary analysis suggests an increase in the exposure to mRNA-3927 with dose escalation, and a 70% reduction in the risk of metabolic decompensation events among 8 participants who reported them in the 12-month pretreatment period.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Propionic Acidemia
/
Propionyl-Coenzyme A Carboxylase
Limits:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
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Infant
/
Male
Language:
En
Journal:
Nature
/
Nature (Lond.)
/
Nature (London)
Year:
2024
Type:
Article
Affiliation country:
United States