Propionic acidaemia Trials in Disease

Study on the Safety and Effectiveness of mRNA-3927 for Patients with Propionic Acidemia

This trial is investigating a new gene therapy approach for treating Propionic Acidaemia using an investigational medication called mRNA-3927. The condition affects how the body breaks down certain proteins and fats, leading to a buildup of harmful substances. This new treatment uses modified messenger RNA delivered through tiny particles to help the body produce the specific enzyme that is missing or not working properly in people with this condition.

Main inclusion criteria:

• Participants must be at least 8 years old if they are among the first two participants in Part 1 of the study, or at least 1 year old if joining later
• Must have a confirmed diagnosis through specific genetic testing
• The participant or their legal representative must be able to give informed consent and follow study assessments
• Sexually active individuals of childbearing potential must agree to use highly effective contraception during the study and for 3 months after the last dose
• For Part 2 only: Must have had at least one documented metabolic decompensation event in the 12 months before consent

Main exclusion criteria:

• Individuals without a confirmed diagnosis cannot participate
• Those outside the specified age range are excluded
• Participants unable to follow study procedures or attend required visits
• Those with other medical conditions that might interfere with the study or pose health risks
• Current or recent participation in another clinical trial
• Pregnant or breastfeeding women
• History of allergic reactions to similar treatments or study medication components
• Recent use of certain medications that could affect study results
• History of substance abuse or behaviors that could interfere with the study

Study focus and goal:

The trial is conducted in two parts. The first part focuses on evaluating the safety and tolerability of mRNA-3927 when given through intravenous infusion directly into a vein. The second part examines how well the treatment works by comparing the frequency of metabolic decompensation events in participants receiving the treatment to those receiving standard care. These events are serious episodes that can occur in people with this condition and can be triggered by illness, fasting, or increased protein intake.

Throughout the study, participants will be carefully monitored for any side effects and changes in their condition. Blood tests will be performed regularly to measure various biological markers and understand how the treatment affects the body. The treatment is given through intravenous infusion, with dosage and frequency determined by the study protocol.

Investigational drug:

mRNA-3927 is a gene therapy medication currently in Phase 1/2 clinical trials. It works by delivering synthetic messenger RNA into cells, which then instructs the cells to produce the enzyme that is deficient in individuals with this condition. The medication aims to address the underlying enzyme deficiency by providing the body with instructions to produce the missing or dysfunctional enzyme propionyl-CoA carboxylase.