An Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3705 in Participants Previously Enrolled in Other Clinical Studies of mRNA-3705

Phase 1

Recruiting

Brief Summary: The primary objective of this study is to evaluate the long-term safety 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 2 years 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 intent to prevent treatment interruption. 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.

Recruitment & Eligibility

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 the mRNA-3705-P101 study.
Completed the End of treatment (EOT) Visit in Study mRNA-3705-P101 within 10 days of first dose of mRNA-3705 in the current 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 exclusion criteria may apply.

Arm && Interventions

Group	Intervention	Description
mRNA-3705	mRNA-3705	Participants will receive mRNA-3705 at the same dose levels at the same dosing interval (every 2 weeks \[Q2W\], or every 3 weeks \[Q3W\]) last received in the clinical study of mRNA-3705 in which they initially participated, unless the Sponsor recommends modification.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (AEs)	Baseline up to follow-up period (up to 8 years)

Secondary Outcome Measures

Name	Time	Method
Change in Methylmalonic Acidemia and Propionic Acidemia Questionnaire Proximal Signs and Symptoms (MMAPAQ-PSS) Score	Baseline up to 8 years
Change in Blood Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 8 Years	Baseline, Year 8
Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels	Baseline up to 6 years
Number of Metabolic Decompensation Events (MDEs)	Baseline up to 8 years
Number of Healthcare Resource Utilization Visits	Baseline up to 8 years
Number of Annualized MMA-related Hospitalizations	Baseline up to 8 years
Number of Annualized MMA-related Healthcare Visits	Baseline up to 8 years
Change in Disease Impact on Missed School and Workdays From Baseline up to 8 Years	Baseline, Year 8
Number of Anti-Polyethylene Glycol (PEG) and Anti-hMUT Antibodies	Baseline up to 8 years
Change in Health-Related Quality of Life (HRQoL) as Measured Using the Pediatric Quality of Life Inventory (PedsQL™) at Month 3 up to 8 Years	Month 3, Year 8
Change in Caregiver Reported Global Impression of Severity (CrGI-S) Score	Baseline up to 8 years
Change in Caregiver Reported Global Impression of Improvement (CrGI-I) Score	Baseline up to 8 years
Change in Investigator Global Assessment of Improvement (IGA-I) Score	Baseline up to 8 years
Change in Investigator Global Assessment of Severity (IGA-S) Score	Baseline up to 8 years
Change in EuroQoL 5-Dimensions 5-level/Youth Questionnaire (EQ-5D-5L/Y) Score	Baseline up to 8 years

Locations (10): UCLA Medical Center
🇺🇸
Los Angeles, California, United States
Lucile Packard Children's Hospital at Stanford
🇺🇸
Palo Alto, California, United States
Stollery Children's Hospital University of Alberta
🇨🇦
Edmonton, Alberta, Canada
Hospital For Sick Children
🇨🇦
Toronto, Ontario, Canada
Hôpital Necker - Enfants Malades APHP
🇫🇷
Paris, France
Erasmus MC
🇳🇱
Rotterdam, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱
Utrecht, Netherlands
Hospital Universitario Cruces
🇪🇸
Barakaldo, Vizcaya, Spain
Birmingham Children's Hospital NHS Foundation Trust
🇬🇧
Birmingham, United Kingdom
Royal Manchester Childrens Hospital
🇬🇧
Manchester, United Kingdom