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

Methylmalonic Acidemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05295433
• Other study ID #: mRNA-3705-P101-EXT
• Secondary ID: 2021-000446-17
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 8, 2022
• Est. completion date: April 2, 2034

Study information

• Verified date: February 2024
• Source: ModernaTX, Inc.
• Contact: Moderna Clinical Trials Support Center
• Phone: 1-877-777-7187
• Email: clinicaltrials[@]modernatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 63
• Est. completion date: April 2, 2034
• Est. primary completion date: April 1, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

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.

Related Conditions & MeSH terms

• Methylmalonic Acidemia

Intervention

Drug:
• mRNA-3705
A sterile liquid for injection

Locations

Country	Name	City	State
Canada	Stollery Children's Hospital University of Alberta	Edmonton	Alberta
Canada	Hospital For Sick Children	Toronto	Ontario
Netherlands	Erasmus MC	Rotterdam
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
United Kingdom	Birmingham Children's Hospital NHS Foundation Trust	Birmingham
United Kingdom	Royal Manchester Childrens Hospital	Manchester
United States	UCLA Medical Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
ModernaTX, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (AEs)		Baseline up to follow-up period (up to 8 years)
Secondary	Change in Blood Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 8 Years		Baseline, Year 8
Secondary	Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels		Baseline up to 6 years
Secondary	Number of Metabolic Decompensation Events (MDEs)		Baseline up to 8 years
Secondary	Number of Healthcare Resource Utilization Visits		Baseline up to 8 years
Secondary	Number of Annualized MMA-related Hospitalizations		Baseline up to 8 years
Secondary	Number of Annualized MMA-related Healthcare Visits		Baseline up to 8 years
Secondary	Change in Disease Impact on Missed School and Workdays From Baseline up to 8 Years		Baseline, Year 8
Secondary	Number of Anti-Polyethylene Glycol (PEG) and Anti-hMUT Antibodies		Baseline up to 8 years
Secondary	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
Secondary	Change in Methylmalonic Acidemia and Propionic Acidemia Questionnaire Proximal Signs and Symptoms (MMAPAQ-PSS) Score		Baseline up to 8 years
Secondary	Change in Caregiver Reported Global Impression of Severity (CrGI-S) Score		Baseline up to 8 years
Secondary	Change in Caregiver Reported Global Impression of Improvement (CrGI-I) Score		Baseline up to 8 years
Secondary	Change in Investigator Global Assessment of Improvement (IGA-I) Score		Baseline up to 8 years
Secondary	Change in Investigator Global Assessment of Severity (IGA-S) Score		Baseline up to 8 years
Secondary	Change in EuroQoL 5-Dimensions 5-level/Youth Questionnaire (EQ-5D-5L/Y) Score		Baseline up to 8 years