Phase 1/2 study of mRNA-3705 in participants with Isolated MMA (Extension Study)
Research type
Research Study
Full title
A Phase 1/2, Global, Open Label, Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in the mRNA-3705-P101 Study
IRAS ID
1004273
Contact name
Ruchira Glaser
Contact email
Sponsor organisation
ModernaTX, Inc.
Eudract number
2021-000446-17
Research summary
Isolated methylmalonic acidemia (MMA) is Rare disorder that occurs in approximately 1 out of 50,000 to 100,000 individuals. It mainly affects the pediatric population with onset in early infancy. The majority of patients have no functional enzyme (mut 0) with the remaining patients having some activity for a milder phenotype (Mut -). Mortality is significant in this disorder, with mortality rates of approximately 50% for patients with complete MUT deficiency (Mut0; median age of death, 2 years) and 40% for patients with partial MUT deficiency (Mut- ; median age of death, 4.5 years) There are no approved therapies to treat MMA associated with MUT deficiency. Standard of care includes dietary restriction, cofactor therapy, and carnitine. Liver and/or kidney transplant is the only effective treatment, even in infants.
Moderna is developing a novel intravenously (IV) administered, lipid encapsulated messenger ribonucleic acid (mRNA)-based therapy that encodes a normal human MUT (hMUT), the enzyme most frequently mutated in MMA. Administration of mRNA-3705 to patients with MUT deficiency is anticipated to restore endogenous production of enzymatically active MUT protein in the mitochondria of liver cells, thus restoring flux through the propionate metabolism pathway in the liver and ameliorating manifestations of the disease by addressing the primary metabolic defect. This is a phase I/II global, multi-centre, open label extension study in participants previously enrolled in the mRNA-3705-P101 Study, with MMA with MUT deficiency to assess the long-term Safety and Clinical Activity of mRNA-3705.
The study will include 2 periods: 1) Treatment Period (6 years) and 2) Follow-up Period (up to 2 years after the last dose of study drug). Participants will be on this study for around 8 years, they will enter the study receiving mRNA-3705 at the same dose and dosing interval last received in the mRNA-3705-P101 study unless the sponsor recommends modification.REC name
South Central - Oxford A Research Ethics Committee
REC reference
21/SC/0346
Date of REC Opinion
17 Dec 2021
REC opinion
Favourable Opinion