Methylmalonic Acidemia
Conditions
Keywords
Isolated Methylmalonic acidemia, Isolated methylmalonic aciduria, Elevated methylmalonic acid (MMA), Metabolism, Inborn Errors, Genetic Diseases, Moderna, mRNA, mRNA-3705
Brief summary
The primary objective of this study is to evaluate the long-term safety and clinical activity of mRNA-3705 administered to participants with isolated methylmalonic acidemia (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency who have previously participated in other clinical studies of mRNA-3705.
Detailed description
Participants with isolated MMA due to MUT deficiency who were previously enrolled in other clinical studies of mRNA-3705 will have the option to enroll into this extension study provided all eligibility criteria have been met. The study will include 2 periods: 1) Treatment Period and 2) Follow-up Period (up to 6 months after the last dose of study drug). Treatment Period will continue unless one of the following occurs: mRNA-3705 receives marketing approval and reimbursement in the country of origin of the participant (following market approval and access being in place, all participants who wish to continue treatment will be offered mRNA-3705 through market access, with the intention of preventing treatment interruption. Other appropriate access program is offered as allowed by local regulation to continue treatment with mRNA-3705. Safety monitoring will be performed for all participants under treatment per market access requirements), the participant discontinues study drug, the participant is no longer receiving clinical benefit in the opinion of the Investigator, or Sponsor discontinues the development of mRNA-3705.
Interventions
DRUGmRNA-3705
A sterile liquid for injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Completed the assigned dose regimen treatment time period in other clinical studies of mRNA-3705 or is eligible for early transition to this study because they missed more than 3 consecutive doses of study drug due to coronavirus disease 2019 (COVID-19) vaccination during Study mRNA-3705-P101 Part 1. * Completed the End of treatment (EOT) Visit (or End of Study Visit in the case of unscheduled dosing) in Study mRNA-3705-P101 within 10 days of their first dose of mRNA-3705 in this extension study.
Exclusion criteria
* Not expected to receive clinical benefit from continued mRNA-3705 administration, in the opinion of the Investigator. * Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the individual at increased risk by participating in this study. * History of liver and/or kidney transplant. NOTE: Other inclusion and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Drug-Related TEAEs, Unrelated TEAEs, Adverse Events of Special Interests (AESIs), Serious Adverse Events (SAEs) and TEAEs Leading to Discontinuation | Baseline up to follow-up period (up to 6 years + 6 months) |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change in Plasma Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 18 Months | Baseline, Year 6 (Treatment Period) + Month 6 (Follow up) |
| Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels | Baseline up to 6 years |
| Change From Baseline in Pretreatment and Post-treatment Annualized Metabolic Decompensation Events (MDEs) Rate | Baseline, Year 6 (Treatment Period) + Month 6 (Follow up) |
| Number of Healthcare Resource Utilization Visits | Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up) |
| Number of Annualized MMA-related Hospitalizations | Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up) |
| Change in EuroQoL 5-Dimensions 5-level/Youth Questionnaire (EQ-5D-5L/Y) Score | Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up) |
| Number of Anti-Polyethylene Glycol (PEG) and Anti-hMUT Antibodies | Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up) |
| Change in Health-Related Quality of Life (HRQoL) as Measured Using the Pediatric Quality of Life Inventory (PedsQL™) at Month 3 up to 18 Months | Month 3, Year 6 (Treatment Period) + Month 6 (Follow up) |
| Change in Investigator Global Assessment of Improvement (IGA-I) Score | Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up) |
| Change in Investigator Global Assessment of Severity (IGA-S) Score | Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up) |
| Number of Annualized MMA-related Healthcare Visits | Baseline up to Year 6 (Treatment Period) + Month 6 (Follow up) |
Countries
Canada, France, Netherlands, Spain, United Kingdom, United States
Contacts
Primary ContactModerna WeCare Team
Outcome results
None listed