A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia
Primary Purpose
Methylmalonic Acidemia
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
mRNA-3705
Sponsored by
About this trial
This is an interventional treatment trial for Methylmalonic Acidemia focused on measuring Isolated Methylmalonic acidemia, Isolated methylmalonic aciduria, elevated methylmalonic acid (MMA), Metabolism, Inborn Errors, Genetic Diseases, Moderna, mRNA, mRNA-3705
Eligibility Criteria
Key Inclusion Criteria:
- Participant has a body weight of ≥11.0 kilograms (kg) at the Screening Visit.
- Participant has a diagnosis of isolated MMA due to MUT deficiency confirmed by molecular genetic testing.
- Participant has a serum/plasma vitamin B12 level equal to or above the lower limit of normal (based on laboratory reference range) confirmed in the Screening Period. For those participants found to have an elevated serum/plasma vitamin B12 level, the participant may enter if, in the opinion of the Investigator, the cause of the elevation is secondary to B12 supplementation.
- Participant or his/her legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulations and willing and able to comply with study-related assessments.
- Sexually active females of childbearing potential and sexually active males of reproductive potential agree to use a highly-effective method of contraception during the study and for 3 months after the last administration of study drug.
Key Exclusion Criteria:
- Participant has a diagnosis of isolated MMA cb1A, cb1B, or cb1D enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria.
- Participant has previously received gene therapy for the treatment of MMA.
- Participant has a history of organ transplantation.
- Participant has an active, unstable, or clinically significant medical condition not related to MMA or history of noncompliance that, in the Investigator's opinion, could potentiate the risk while participating in this study, interfere with the interpretation of study results, or limit the participant's participation in the study. This may include, but is not limited to, history of relevant food or drug allergies; history of cardiovascular, central nervous, gastrointestinal, or infectious disease; history of clinically significant pathology; and/or history of cancer.
Sites / Locations
- UCLA Medical CenterRecruiting
- Lucile Packard Children's Hospital at StanfordRecruiting
- The Children's Hospital of PhiladelphiaRecruiting
- Stollery Children's Hospital University of AlbertaRecruiting
- Hospital For Sick ChildrenRecruiting
- Erasmus MCRecruiting
- Universitair Medisch Centrum UtrechtRecruiting
- Birmingham Children's Hospital NHS Foundation Trust
- Royal Manchester Childrens HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
mRNA-3705
Arm Description
Treatment Period (during the Dose Optimization Stage and the Optional Dose Expansion Stage): 1 of up to 5 possible doses of mRNA-3705, administered intravenously (IV), once every 2 to 4 weeks (q2W to q4W), depending on participant's weight for up to 10 doses over approximately 40 weeks.
Outcomes
Primary Outcome Measures
The Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Study Drug-related TEAES, Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation
Secondary Outcome Measures
Change in Plasma Methylmalonic Acid Level
Maximum Observed Effect (Emax) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Area Under the Effect Curve (AUEC) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Duration of Response for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Change in 2-Methylcitric Acid (2-MC ) Levels
Maximum Observed Concentration (Cmax) of human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA-3705
Area Under the Concentration-Time Curve (AUC) of hMUT mRNA-3705
Titer of Anti-Polyethylene Glycol (PEG) Antibodies
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04899310
Brief Title
A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia
Official Title
A Global, Phase 1/2, Open-Label, Dose Optimization Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia Due to Methylmalonyl-CoA Mutase Deficiency
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 6, 2021 (Actual)
Primary Completion Date
August 1, 2026 (Anticipated)
Study Completion Date
August 1, 2028 (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
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a study of mRNA-3705 in participants with isolated elevated methylmalonic acid (MMA) due to methylmalonyl-coenzyme A (CoA) mutase (MUT) deficiency. The main goal of the study is to assess safety, pharmacokinetics, and pharmacodynamics of mRNA-3705.
Detailed Description
This study comprises 2 stages; a Dose Optimization Stage followed by an optional Dose Expansion Stage. The study is designed to evaluate multiple doses and dosing intervals of mRNA-3705.
In both stages, after confirmation of eligibility, participants will enter an Observation Period (48 to 72 hours pre-dose), which includes 24 hours inpatient hospital stay, followed by a Treatment Period (up to 40 weeks). Participants who complete the Treatment Period, including the End of Treatment (EOT) Visit, are offered participation in the mRNA-3705 extension study. If the participant chooses to participate and meets eligibility criteria, they will be enrolled in the extension study; otherwise, they will transition to the 2-year follow-up part of this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Methylmalonic Acidemia
Keywords
Isolated Methylmalonic acidemia, Isolated methylmalonic aciduria, elevated methylmalonic acid (MMA), Metabolism, Inborn Errors, Genetic Diseases, Moderna, mRNA, mRNA-3705
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
33 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
mRNA-3705
Arm Type
Experimental
Arm Description
Treatment Period (during the Dose Optimization Stage and the Optional Dose Expansion Stage): 1 of up to 5 possible doses of mRNA-3705, administered intravenously (IV), once every 2 to 4 weeks (q2W to q4W), depending on participant's weight for up to 10 doses over approximately 40 weeks.
Intervention Type
Biological
Intervention Name(s)
mRNA-3705
Other Intervention Name(s)
modified mRNA encoding human, methylmalonyl-coenzyme A mutase
Intervention Description
A sterile liquid for injection
Primary Outcome Measure Information:
Title
The Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Study Drug-related TEAES, Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation
Time Frame
Up to 144 weeks
Secondary Outcome Measure Information:
Title
Change in Plasma Methylmalonic Acid Level
Time Frame
Baseline up to Week 40
Title
Maximum Observed Effect (Emax) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Time Frame
Baseline up to Week 40
Title
Area Under the Effect Curve (AUEC) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Time Frame
Baseline up to Week 40
Title
Duration of Response for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705
Time Frame
0 (predose) up to 336 hours postdose
Title
Change in 2-Methylcitric Acid (2-MC ) Levels
Time Frame
Baseline up to Week 40
Title
Maximum Observed Concentration (Cmax) of human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA-3705
Time Frame
0 (predose) to 336 hours postdose
Title
Area Under the Concentration-Time Curve (AUC) of hMUT mRNA-3705
Time Frame
0 (predose) to 336 hours postdose
Title
Titer of Anti-Polyethylene Glycol (PEG) Antibodies
Time Frame
0 (predose) to 336 hours postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Participant has a body weight of ≥11.0 kilograms (kg) at the Screening Visit.
Participant has a diagnosis of isolated MMA due to MUT deficiency confirmed by molecular genetic testing.
Participant has a serum/plasma vitamin B12 level equal to or above the lower limit of normal (based on laboratory reference range) confirmed in the Screening Period. For those participants found to have an elevated serum/plasma vitamin B12 level, the participant may enter if, in the opinion of the Investigator, the cause of the elevation is secondary to B12 supplementation.
Participant or his/her legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulations and willing and able to comply with study-related assessments.
Sexually active females of childbearing potential and sexually active males of reproductive potential agree to use a highly-effective method of contraception during the study and for 3 months after the last administration of study drug.
Key Exclusion Criteria:
Participant has a diagnosis of isolated MMA cb1A, cb1B, or cb1D enzymatic subtypes or methylmalonyl-CoA epimerase deficiency or combined MMA with homocystinuria.
Participant has previously received gene therapy for the treatment of MMA.
Participant has a history of organ transplantation.
Participant has an active, unstable, or clinically significant medical condition not related to MMA or history of noncompliance that, in the Investigator's opinion, could potentiate the risk while participating in this study, interfere with the interpretation of study results, or limit the participant's participation in the study. This may include, but is not limited to, history of relevant food or drug allergies; history of cardiovascular, central nervous, gastrointestinal, or infectious disease; history of clinically significant pathology; and/or history of cancer.
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
UCLA Medical Center
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
Kara Ha
Email
ksha@mednet.ucla.edu
Facility Name
Lucile Packard Children's Hospital at Stanford
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hershonna Robinson
Email
hsrobin@stanford.edu
Facility Name
The 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
Stollery Children's Hospital University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2R7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheri Copithorne
Email
cheri.robert@ahs.ca
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
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015 AA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
Email
m.wagenmakers@erasmusmc.nl
First Name & Middle Initial & Last Name & Degree
Margreet Wagenmakers
Facility Name
Universitair Medisch Centrum Utrecht
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
Email
S.Michel-2@umcutrecht.nl
First Name & Middle Initial & Last Name & Degree
Sabine Fuchs
Facility Name
Birmingham Children's Hospital NHS Foundation Trust
City
Birmingham
Country
United Kingdom
Individual Site Status
Active, not recruiting
Facility Name
Royal Manchester Childrens Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laura Crowther
Email
genetics.research@mft.nhs.uk
12. IPD Sharing Statement
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A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia
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