Phase 1/ 2 study of mRNA-3705 in participants with Isolated MMA

• Research type

  Research Study

• Full title

  A Global, Phase 1/2, Open-Label, Dose Optimization Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of mRNA-3705 in Participants with Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency

• IRAS ID

  1003618

• Contact name

  Tal Zaks

• Contact email

  Tal.Zaks@modernatx.com

• Sponsor organisation

  ModernaTX, Inc.

• Eudract number

  2020-004980-24

• Clinicaltrials.gov Identifier

  NCT04899310

• 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 more mild 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 study in patients ≥1 years of age with Isolated methylmalonic acidemia (MMA) with MUT deficiency to assess the safety and response of mRNA-3705.
  Participants will be in the study for up to almost 3 years and may visit the study centre up to about 81 times. Participants will receive up to 10 doses of the study drug and may then be given the opportunity for more treatment in an extension study or follow-up period which will last about years. Participants will get an infusion of the study drug every 2, 3 or 4 weeks

• REC name

  South Central - Oxford A Research Ethics Committee

• REC reference

  21/SC/0055

• Date of REC Opinion

  15 Apr 2021

• REC opinion

  Further Information Favourable Opinion