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

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 Other Clinical Studies of mRNA-3705

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.

Study Overview

• Status: Recruiting
• Conditions: Methylmalonic Acidemia
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Moderna Clinical Trials Support Center; Phone Number: 1-877-777-7187; Email: clinicaltrials@modernatx.com

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R7
      • Recruiting
      • Stollery Children's Hospital University of Alberta
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Recruiting
      • Hospital for Sick Children
• Netherlands
  • Rotterdam, Netherlands, 3015 AA
    • Recruiting
    • Erasmus MC
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • Universitair Medisch Centrum Utrecht
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Active, not recruiting
    • Birmingham Children's Hospital NHS Foundation Trust
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Royal Manchester Childrens Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: mRNA-3705; A sterile liquid for injection; Other Names: modified mRNA encoding human; methylmalonyl-coenzyme A mutase

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Metabolic Decompensation Events (MDEs)	Baseline up to 8 years
Number of Healthcare Resource Utilization Visits	Baseline up to 8 years
Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels	Baseline up to 6 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 Blood Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 8 Years	Baseline, Year 8
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 Methylmalonic Acidemia and Propionic Acidemia Questionnaire Proximal Signs and Symptoms (MMAPAQ-PSS) Score	Baseline up to 8 years
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

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2022
• Primary Completion (Estimated): April 1, 2032
• Study Completion (Estimated): April 2, 2034

Study Registration Dates

• First Submitted: February 14, 2022
• First Submitted That Met QC Criteria: March 16, 2022
• First Posted (Actual): March 25, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Moderna; mRNA; Genetic Diseases; Metabolism, Inborn Errors; Isolated Methylmalonic acidemia; Isolated methylmalonic aciduria; mRNA-3705; Elevated methylmalonic acid (MMA)
• Other Study ID Numbers: mRNA-3705-P101-EXT; 2021-000446-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes