Clinical trial NCT05295433: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Methylmalonic Acidemia
Keywords: Isolated Methylmalonic acidemia
Isolated methylmalonic aciduria
Elevated methylmalonic acid (MMA)
Metabolism, Inborn Errors
Genetic Diseases
Moderna
mRNA
mRNA-3705
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-25
Enrollment: 63
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs)
timeFrame: Baseline up to follow-up period (up to 8 years)
Secondary outcomes:
measure: Change in Blood Methylmalonic Acid and 2-Methylcitric Acid (2-MC) Levels (Primary Biomarkers) From Baseline up to 8 Years
timeFrame: Baseline, Year 8
measure: Pre- and Postdose Human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA and SM-86 Levels
timeFrame: Baseline up to 6 years
measure: Number of Metabolic Decompensation Events (MDEs)
timeFrame: Baseline up to 8 years
measure: Number of Healthcare Resource Utilization Visits
timeFrame: Baseline up to 8 years
measure: Number of Annualized MMA-related Hospitalizations
timeFrame: Baseline up to 8 years
measure: Number of Annualized MMA-related Healthcare Visits
timeFrame: Baseline up to 8 years
measure: Change in Disease Impact on Missed School and Workdays From Baseline up to 8 Years
timeFrame: Baseline, Year 8
measure: Number of Anti-Polyethylene Glycol (PEG) and Anti-hMUT Antibodies
timeFrame: Baseline up to 8 years
measure: 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
timeFrame: Month 3, Year 8
measure: Change in Methylmalonic Acidemia and Propionic Acidemia Questionnaire Proximal Signs and Symptoms (MMAPAQ-PSS) Score
timeFrame: Baseline up to 8 years
measure: Change in Caregiver Reported Global Impression of Severity (CrGI-S) Score
timeFrame: Baseline up to 8 years
measure: Change in Caregiver Reported Global Impression of Improvement (CrGI-I) Score
timeFrame: Baseline up to 8 years
measure: Change in Investigator Global Assessment of Improvement (IGA-I) Score
timeFrame: Baseline up to 8 years
measure: Change in Investigator Global Assessment of Severity (IGA-S) Score
timeFrame: Baseline up to 8 years
measure: Change in EuroQoL 5-Dimensions 5-level/Youth Questionnaire (EQ-5D-5L/Y) Score
timeFrame: Baseline up to 8 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford
state: California
city: Edmonton
country: Canada
facility: Stollery Children's Hospital University of Alberta
state: Alberta
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
city: Paris
country: France
facility: Hôpital Necker - Enfants Malades APHP
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Barakaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: Royal Manchester Childrens Hospital
Study officials:
References: