Back to resultsOpen-Label Study of mRNA-3927 in Participants With Propionic Acidemia
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:
- Participant must be ≥ 8 years of age at the time of consent/assent if enrolled as 1 of the first 2 participants.
- Participant must be ≥1 year of age at the time of consent/assent if enrolled after the first 2 participants.
- Confirmed diagnosis of propionic acidemia based on diagnosis by molecular genetic testing (propionyl-CoA carboxylase subunit α [PCCA] and/or propionyl CoA carboxylase subunit β [PCCB] mutations)
Exclusion Criteria:
- Estimated glomerular filtration rate <30 milliliters (mL)/minute/1.73 square meter (m^2) as estimated by Schwartz formula for participants < 18 years of age or the Chronic Kidney Disease Epidemiology Collaboration creatinine based formula for participants ≥ 18 years of age or for participants of all ages receiving chronic dialysis.
- History of organ transplantation or planned organ transplantation during the period of study participation.
- Corrected QT interval (QTc) >480 milliseconds (ms) using Bazett's correction.
- Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association Classification.
- COVID-19 vaccination (generally 2 doses or a booster) within 6 weeks between their last COVID-19 vaccination dose and first study drug administration.
Sites / Locations
- David Geffen School of Medicine UCLARecruiting
- University of Stanford Medical CenterRecruiting
- Johns Hopkins HospitalRecruiting
- Boston Children's HospitalRecruiting
- University of MichiganRecruiting
- Icahn School of Medicine at Mount Sinai - Clinical Research UnitRecruiting
- Duke University Medical CenterRecruiting
- Cincinnati Children's HospitalRecruiting
- Children's Hospital of PhiladelphiaRecruiting
- Texas Children's HospitalRecruiting
- Hospital For Sick ChildrenRecruiting
- University Hospital Birmingham NHS Foundation TrustRecruiting
- Birmingham Children's Hospital
- Great Ormond Street Hospital (GOSH)Recruiting
- Willink Biochemical Genetics UnitRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Dose Optimization Stage: Dose Level 1
Dose Optimization Stage: Dose Level 2
Dose Optimization Stage: Dose Level 3
Dose Optimization Stage: Dose Level 4
Dose Optimization Stage: Dose Level 5
Dose Optimization Stage: Dose Level 6
Dose Expansion Stage
Arm Description
Participants will receive 1 dose of Dose Level 1 of mRNA-3927 by intravenous (IV) infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.
Participants will receive 1 dose of Dose Level 2 of mRNA-3927 by IV infusion once every 2 weeks during the approximate 20-week Treatment Period.
Participants will receive 1 dose of Dose Level 3 of mRNA-3927 by IV infusion once every 2 weeks during the approximate 20-week Treatment Period.
Participants will receive 1 dose of Dose Level 4 of mRNA-3927 by IV infusion at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Participants will receive 1 dose of Dose Level 5 of mRNA-3927 by IV infusion at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Participants will receive 1 dose of Dose Level 6 of mRNA-3927 by IV infusion at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Participant will receive the optimal dose of mRNA-3927 identified during the Dose Optimization Stage at 1 dose at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Outcomes
Primary Outcome Measures
Number of Participants with an Adverse Event (AE)
Secondary Outcome Measures
Maximum Observed Concentration (Cmax) after Administration of mRNA-3927
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927
Time of Cmax (Tmax)
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927
Area Under the Plasma Concentration-Time Curve (AUC)
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927
Frequency of Anti-Polyethylene Glycol Antibodies
Change from Baseline in Plasma 2-Methylcitrate (2-MC) Levels at Week 40
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927.
Change from Baseline in Plasma 3-Hydroxypropionic Acid (3-HP) Levels at Week 40
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04159103
Brief Title
Open-Label Study of mRNA-3927 in Participants With Propionic Acidemia
Official Title
A Global, Phase 1/2, Open-Label, Dose Optimization Study to Evaluate the Safety, Pharmacodynamics, and Pharmacokinetics of mRNA-3927 in Participants With Propionic Acidemia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 15, 2021 (Actual)
Primary Completion Date
March 5, 2025 (Anticipated)
Study Completion Date
January 6, 2027 (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
This First-in-Human (FIH) Phase 1/2 study will evaluate the safety and pharmacological activity of mRNA-3927 in participants 1 year of age and older with genetically confirmed propionic acidemia (PA). The study is designed to characterize baseline biomarker levels followed by assessment of safety, pharmacokinetics (PK), and pharmacodynamics (PD) of different doses of mRNA-3927 in participants affected by PA as part of the Dose Optimization phase.
Detailed Description
During the Dose Optimization Stage, after each dose cohort is fully enrolled, 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 6 cohorts will be enrolled into the study.
Upon establishment of a dose with acceptable safety and pharmacodynamic activity, additional participants will be enrolled in a Dose Expansion Stage to allow for further characterization of the safety and pharmacodynamics of mRNA-3927.
Participants in both phases of study will participate in a predosing observational period, followed by a treatment period, and then a follow-up period after withdrawal of treatment.
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
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Optimization Stage: Dose Level 1
Arm Type
Experimental
Arm Description
Participants will receive 1 dose of Dose Level 1 of mRNA-3927 by intravenous (IV) infusion on Day 1 of a 21-day period for up to 10 doses during the approximate 30-week Treatment Period.
Arm Title
Dose Optimization Stage: Dose Level 2
Arm Type
Experimental
Arm Description
Participants will receive 1 dose of Dose Level 2 of mRNA-3927 by IV infusion once every 2 weeks during the approximate 20-week Treatment Period.
Arm Title
Dose Optimization Stage: Dose Level 3
Arm Type
Experimental
Arm Description
Participants will receive 1 dose of Dose Level 3 of mRNA-3927 by IV infusion once every 2 weeks during the approximate 20-week Treatment Period.
Arm Title
Dose Optimization Stage: Dose Level 4
Arm Type
Experimental
Arm Description
Participants will receive 1 dose of Dose Level 4 of mRNA-3927 by IV infusion at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Arm Title
Dose Optimization Stage: Dose Level 5
Arm Type
Experimental
Arm Description
Participants will receive 1 dose of Dose Level 5 of mRNA-3927 by IV infusion at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Arm Title
Dose Optimization Stage: Dose Level 6
Arm Type
Experimental
Arm Description
Participants will receive 1 dose of Dose Level 6 of mRNA-3927 by IV infusion at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
Arm Title
Dose Expansion Stage
Arm Type
Experimental
Arm Description
Participant will receive the optimal dose of mRNA-3927 identified during the Dose Optimization Stage at 1 dose at an applicable dosing schedule during the approximate 20-40 week Treatment Period (20 weeks for every two week dosing, 30 weeks for every three week dosing, or 40 weeks for every four week dosing).
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 an Adverse Event (AE)
Time Frame
Day 1 (initial mRNA-3927 dose) up to Week 150 (End of Study)
Secondary Outcome Measure Information:
Title
Maximum Observed Concentration (Cmax) after Administration of mRNA-3927
Description
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927
Time Frame
Day 1 through Day 15
Title
Time of Cmax (Tmax)
Description
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927
Time Frame
Day 1 through Day 15
Title
Area Under the Plasma Concentration-Time Curve (AUC)
Description
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927
Time Frame
Day 1 through Day 15
Title
Frequency of Anti-Polyethylene Glycol Antibodies
Time Frame
Baseline through Week 150
Title
Change from Baseline in Plasma 2-Methylcitrate (2-MC) Levels at Week 40
Description
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927.
Time Frame
Baseline, Week 40
Title
Change from Baseline in Plasma 3-Hydroxypropionic Acid (3-HP) Levels at Week 40
Description
Baseline (predose levels) to postdose levels measured after single and after repeated administrations of mRNA-3927.
Time Frame
Baseline, Week 40
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant must be ≥ 8 years of age at the time of consent/assent if enrolled as 1 of the first 2 participants.
Participant must be ≥1 year of age at the time of consent/assent if enrolled after the first 2 participants.
Confirmed diagnosis of propionic acidemia based on diagnosis by molecular genetic testing (propionyl-CoA carboxylase subunit α [PCCA] and/or propionyl CoA carboxylase subunit β [PCCB] mutations)
Exclusion Criteria:
Estimated glomerular filtration rate <30 milliliters (mL)/minute/1.73 square meter (m^2) as estimated by Schwartz formula for participants < 18 years of age or the Chronic Kidney Disease Epidemiology Collaboration creatinine based formula for participants ≥ 18 years of age or for participants of all ages receiving chronic dialysis.
History of organ transplantation or planned organ transplantation during the period of study participation.
Corrected QT interval (QTc) >480 milliseconds (ms) using Bazett's correction.
Grade 3 or 4 heart failure according to the Modified Ross Heart Failure Classification for Children or the New York Heart Association Classification.
COVID-19 vaccination (generally 2 doses or a booster) within 6 weeks between their last COVID-19 vaccination dose and first study drug administration.
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
David Geffen School of Medicine UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rosemary Silva-Garcia
Email
rsilvagarcia@mednet.ucla.edu
Facility Name
University of Stanford Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
650-497-0454
Email
hsrobin@stanford.edu
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
hvernon1@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Hilary Vernon
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
617-355-6394
Email
Walla.Al-Hertani@childrens.harvard.edu
First Name & Middle Initial & Last Name & Degree
Walla Al-Hertani
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Name
Icahn School of Medicine at Mount Sinai - Clinical Research Unit
City
New York
State/Province
New York
ZIP/Postal Code
10029
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 Contact:
First Name & Middle Initial & Last Name & Degree
Ming Xu
Email
mingfen.xu@duke.edu
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Racheal Powers
Email
Racheal.Powers@cchmc.org
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rebecca Madden
Email
maddenr@chop.edu
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alyssa Tran
Email
alyssat@bcm.edu
Facility Name
Hospital For Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashley Wilson
Email
ashley.wilson@sickkids.ca
Facility Name
University Hospital Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vishy Veeranna
Email
Vishy.veeranna@uhb.nhs.uk
Facility Name
Birmingham Children's Hospital
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
Great Ormond Street Hospital (GOSH)
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
Email
Stephanie.Grunewald@gosh.nhs.uk
First Name & Middle Initial & Last Name & Degree
Stephanie Grunewald
Facility Name
Willink Biochemical Genetics Unit
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
Phone
4401617019137
Email
laura.crowther@mft.nhs.uk
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Open-Label Study of mRNA-3927 in Participants With Propionic Acidemia
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