A Long-Term Extension Study to Evaluate the Safety and Clinical Activity of mRNA-3927
Primary Purpose
Propionic Acidemia
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
mRNA-3927
Sponsored by
About this trial
This is an interventional treatment trial for Propionic Acidemia focused on measuring 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
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.
Sites / Locations
- MichiganRecruiting
- Duke University Medical CenterRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Hospital For Sick ChildrenRecruiting
- University Hospital Birmingham NHS Foundation TrustRecruiting
- Birmingham Children's HospitalRecruiting
- Great Ormond Street Hospital (GOSH)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
mRNA-3927
Arm Description
Participants will receive the applicable dose identified during Study mRNA-3927-P101 (NCT04159103) on Day 1. The dose can be adjusted based on Sponsor recommendation.
Outcomes
Primary Outcome Measures
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Secondary Outcome Measures
Change From Baseline in Plasma 2-Methylcitrate (2-MC) Levels
Change From Baseline in Plasma 3-Hydroxypropionic Acid (3-HP) Levels
Pharmacokinetic (PK): Propionyl-CoA Carboxylase (PCC) Subunit α (PCCA) and Propionyl-CoA Carboxylase Subunit β (PCCB) mRNA (Serum) and SM-86 (Plasma) Levels
Number of Clinically Significant Events
Clinically significant events include hospitalization, emergency room visits, emergency interventions outside of healthcare settings, and complications of cardiomyopathy treated outside of hospital.
Number of Metabolic Decompensation Events (MDEs)
Number of Healthcare Resource Utilization Visits
Number of Days Participants Missed School and Workdays
Number of Anti-Polyethylene Glycol Antibodies
Number of Anti-PCC Antibodies
Change From Baseline in Pediatric Quality-of-Life Inventory (PedsQL)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05130437
Brief Title
A Long-Term Extension Study to Evaluate the Safety and Clinical Activity of mRNA-3927
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 9, 2021 (Actual)
Primary Completion Date
December 4, 2029 (Anticipated)
Study Completion Date
December 4, 2031 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ModernaTX, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
mRNA-3927
Arm Type
Experimental
Arm Description
Participants will receive the applicable dose identified during Study mRNA-3927-P101 (NCT04159103) on Day 1. The dose can be adjusted based on Sponsor recommendation.
Intervention Type
Biological
Intervention Name(s)
mRNA-3927
Intervention Description
mRNA-3927 dispersion for IV infusion
Primary Outcome Measure Information:
Title
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Time Frame
Baseline up to End of Study Visit (up to 8 years)
Secondary Outcome Measure Information:
Title
Change From Baseline in Plasma 2-Methylcitrate (2-MC) Levels
Time Frame
Baseline, End of Study (up to 8 years)
Title
Change From Baseline in Plasma 3-Hydroxypropionic Acid (3-HP) Levels
Time Frame
Baseline, End of Study (up to 8 years)
Title
Pharmacokinetic (PK): Propionyl-CoA Carboxylase (PCC) Subunit α (PCCA) and Propionyl-CoA Carboxylase Subunit β (PCCB) mRNA (Serum) and SM-86 (Plasma) Levels
Time Frame
Predose and End of Infusion up to 8 years postdose
Title
Number of Clinically Significant Events
Description
Clinically significant events include hospitalization, emergency room visits, emergency interventions outside of healthcare settings, and complications of cardiomyopathy treated outside of hospital.
Time Frame
Baseline up to 8 years
Title
Number of Metabolic Decompensation Events (MDEs)
Time Frame
Baseline up to 8 years
Title
Number of Healthcare Resource Utilization Visits
Time Frame
Baseline up to 8 years
Title
Number of Days Participants Missed School and Workdays
Time Frame
Baseline up to 8 years
Title
Number of Anti-Polyethylene Glycol Antibodies
Time Frame
Month 6 up to 8 years
Title
Number of Anti-PCC Antibodies
Time Frame
Month 6 up to 8 years
Title
Change From Baseline in Pediatric Quality-of-Life Inventory (PedsQL)
Time Frame
Baseline, End of Study (up to 8 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Moderna Clinical Trials Support Center
Phone
1-877-777-7187
Email
clinicaltrials@modernatx.com
Facility Information:
Facility Name
Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Name
Hospital For Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Individual Site Status
Recruiting
Facility Name
University Hospital Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Birmingham Children's Hospital
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Great Ormond Street Hospital (GOSH)
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
A Long-Term Extension Study to Evaluate the Safety and Clinical Activity of mRNA-3927
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