Open-Label Study of mRNA-3927 in Participants With Propionic Acidemia
Start Date
4/15/2021
Completion Date
8/31/2027
Summary
This 3-part, Phase 1/2 study is designed to characterize the safety, tolerability, and pharmacological activity (as assessed by biomarker measurements) and to determine the selected dose of mRNA-3927 in participants with genetically confirmed propionic acidemia (PA). After establishing a dose with an acceptable safety and pharmacodynamic (PD) response for participants ≥1 year of age in Part 1, participants will be enrolled in Part 2 (which will serve as the pivotal study) to allow for determination of the efficacy, safety, and PD of mRNA-3927. Part 3 will evaluate the safety, efficacy and PD response of mRNA-3927 in infants (\<1 year of age).
Detailed Description
During the Dose Optimization Stage, after each dose cohort is fully enrolled (≥1 year of age), and the dose-limiting toxicity (DLT) observation window of at least 14 days is complete for the final participant in that cohort, the Sponsor will review the totality of available safety data in conjunction with all available PK/PD data. Based on this review, the Sponsor will recommend a revised dose and/or dosing interval. The Sponsor will abide by predefined constraints as to the maximum percentage change in dose and dose interval. A maximum of 9 cohorts will be enrolled in Part 1 (Dose Optimization). Upon establishment of a dose with an acceptable safety and PD activity in Part 1 (participants ≥1 year of age), additional participants will be enrolled into the study in Part 2 (participants ≥1 year of age) to allow for determination of the safety, efficacy, and PD of mRNA-3927. Part 3 will evaluate the safety, efficacy and PD response in infants (\<1 year of age). Participants in all the phases will participate in a predosing observational period, followed by a treatment period, and then a follow-up period after withdrawal of treatment.
Eligibility Criteria
Age Range: No minimum to No maximum
Interventions
mRNA-3927
Conditions
Locations
UCSD Altman Clinical and Transalational Research Institute Building
Los Angeles, California 90027
United States
Ronald Reagan UCLA Medical Center
Los Angeles, California 90095
United States
Lucile Packard Children's Hospital Stanford
Stanford, California 94304
United States
Nicklaus Children's Hospital
Miami, Florida 33155
United States
University of South Florida - 12901 Bruce B Downs
Tampa, Florida 33606-3603
United States
Ann and Robert H Lurie Childrens Hospital of Chicago
Chicago, Illinois 60611
United States
Johns Hopkins Hospital, Adult Outpatient Clinical Research Unit
Baltimore, Maryland 21287
United States
Boston Children's Hospital
Boston, Massachusetts 02115
United States
University of Michigan Hospitals
Ann Arbor, Michigan 48109
United States
Icahn School of Medicine at Mount Sinai - Clinical Research Unit
New York, New York 10029
United States
Duke University Medical System (Duke Health)
Durham, North Carolina 27710
United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio 45229
United States
University Hospitals Cleveland Medical Center - 11100 Euclid Ave
Cleveland, Ohio 44106-2624
United States
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania 19104
United States
Texas Children's Hospital
Houston, Texas 77030
United States
Stollery Children's Hospital University of Alberta
Edmonton, Alberta T6G 2R7
Canada
Hospital For Sick Children
Toronto, Ontario M5G 1X8
Canada
CHU de Marseille - Hôpital de la Timone
Marseille, 13005
France
Hôpital Necker - Enfants Malades
Paris, 75019
France
Fujita Health University Hospital
Toyoake-shi, Aichi-ken 470-1192
Japan
Tohoku University Hospital
Sendai, Miyagi 980-8574
Japan
National Center for Child Health and Development
Tokyo, 113-8519
Japan
Erasmus MC
Rotterdam, South Holland 3015 GD
Netherlands
Universitair Medisch Centrum Utrecht - PPDS
Utrecht, 3584 CX
Netherlands
King Faisal Specialist Hospital & Research Center - Riyadh
Riyadh, Ar Riya 11211
Saudi Arabia
King Fahad Medical City
Riyadh, Ar Riya 11564
Saudi Arabia
King Abdullah Children's Specialist Hospital
Riyadh, Ar Riya 14611
Saudi Arabia
Hospital Sant Joan de Deu - PIN
Esplugues de Llobregat, Barcelona 8950
Spain
Hospital Universitario Cruces
Barakaldo, Biscay 48903
Spain
Hospital Universitario 12 de Octubre
Madrid, 28041
Spain
Hospital Universitario Virgen del Rocio - PPDS
Seville, 41013
Spain
University Hospital Birmingham NHS Foundation Trust
Birmingham, B15 2TH
United Kingdom
Birmingham Children's Hospital
Birmingham, B4 6NH
United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust
London, WC1N 3JH
United Kingdom
Willink Biochemical Genetics Unit - PPDS
Manchester, M13 9WL
United Kingdom