Clinical trial NCT05130437: A Study to Assess the Long-term Safety and Clinical Activity of mRNA-3927 in Participants Previously Enrolled in the mRNA-3927-P101 Study
Official title: A Phase 1/2, Global, Open-Label, Extension Study to Evaluate the Long-Term Safety and Clinical Activity of mRNA-3927 in Participants Previously Enrolled in the mRNA-3927-P101 Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Propionic Acidemia
Keywords: mRNA-3927
Propionic Aciduria
Metabolism, Inborn Errors
Genetic Diseases
Inborn Amino Acid Metabolism, Inborn Errors
Acidosis
Acid-Base Imbalance
Metabolic Diseases
Organic Acidemias
Moderna
mRNA
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2021-11-23
Enrollment: 36
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 main purpose of this study is to evaluate the long-term safety of mRNA-3927 administered to participants with propionic acidemia (PA) who have previously participated in Study mRNA-3927-P101 (NCT04159103).

Detailed description: The study will assess long-term safety and clinical activity of mRNA-3927. Participants with PA who were previously enrolled and completed the end-of-treatment (EOT) Visit of the mRNA-3927-P101 study 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). All participants will enter the study receiving mRNA-3927 at the same dose and at the same dosing interval last received in the mRNA-3927-P101 study.

Eligibility criteria: Inclusion Criteria:

* Participated in Study mRNA-3927-P101.
* Completed the EOT Visit in Study mRNA-3927-P101 within 10 days of first dose of mRNA-3927 in current study.

Exclusion Criteria:

* Not expected to receive clinical benefit from continued mRNA-3927 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.

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs), Serious AEs (SAEs), and AEs Leading to Discontinuation
timeFrame: Baseline through End of Study Visit (up to 8 years)
measure: Annualized Frequency of Metabolic Decompensation Events (MDEs)
timeFrame: Month 6 through End of Study (up to 8 years)
Secondary outcomes:
measure: Annualized Duration of MDEs
timeFrame: Month 6 through End of Study (up to 8 years)
measure: Annualized Frequency of PA-related Hospitalizations
timeFrame: Baseline through End of Study (up to 8 years)
measure: Change From Pretreatment Prescribed Protein Intake
timeFrame: Baseline, End of Study (up to 8 years)
measure: Change From Pretreatment in Pediatric Quality-of-Life Inventory (PedsQL)
timeFrame: Baseline, End of Study (up to 8 years)
measure: Change From Pretreatment in PedsQL Family Impact Module
timeFrame: Baseline, End of Study (up to 8 years)
measure: Change From Pretreatment in Methylmalonic Acidemia and Propionic Acidemia Questionnaire-Proximal Signs and Symptoms (MMAPAQ-PSS)
timeFrame: Baseline, End of Study (up to 8 years)
measure: Change From Pretreatment in Investigator Global Assessment of Improvement (IGA- I)
timeFrame: Baseline, End of Study (up to 8 years)
measure: Change From Pretreatment in Investigator Global Assessment of Severity (IGA-S)
timeFrame: Baseline, End of Study (up to 8 years)
measure: Change in 2-Methylcitrate and 3-Hydroxypropionic Acid
timeFrame: Month 3, End of Study (up to 8 years)
measure: Number of Anti-polyethylene Glycol Antibodies
timeFrame: Month 3 through End of Study (up to 8 years)
measure: Number of Anti-propionyl-CoA Carboxylase (PCC) Antibodies
timeFrame: Month 3 through End of Study (up to 8 years)
measure: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Propionyl-CoA Carboxylase Subunit Alpha (PCCA) mRNA and Propionyl-CoA Carboxylase Subunit Beta (PCCB) mRNA
timeFrame: Month 3 through Month 72 (predose, end of infusion)
measure: PK: Area Under the Curve (AUC) of PCCA mRNA and PCCB mRNA
timeFrame: Month 3 through Month 72 (predose, end of infusion)
measure: SM-86 Plasma Concentration After Single and Repeated Dosing
timeFrame: Month 3 through Month 72 (predose, end of infusion)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Ann Arbor
country: United States
facility: University of Michigan Hospitals
state: Michigan
city: Durham
country: United States
facility: Duke University Medical System (Duke Health)
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia (CHOP)
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
city: Manchester
country: United Kingdom
facility: Willink Biochemical Genetics Unit - Manchester
state: England
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
Study officials:
References: