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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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ClinicalTrials.gov Identifier: NCT04899310
Recruitment Status : Recruiting
First Posted : May 24, 2021
Last Update Posted : March 9, 2023
Information provided by (Responsible Party):
ModernaTX, Inc.

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.

Condition or disease Intervention/treatment Phase
Methylmalonic Acidemia Biological: mRNA-3705 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 6, 2021
Estimated Primary Completion Date : August 1, 2026
Estimated Study Completion Date : August 1, 2028

Arm Intervention/treatment
Experimental: mRNA-3705
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.
Biological: mRNA-3705
A sterile liquid for injection
Other Names:
  • modified mRNA encoding human
  • methylmalonyl-coenzyme A mutase

Primary Outcome Measures :
  1. 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 Measures :
  1. Change in Plasma Methylmalonic Acid Level [ Time Frame: Baseline up to Week 40 ]
  2. Maximum Observed Effect (Emax) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705 [ Time Frame: Baseline up to Week 40 ]
  3. 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 ]
  4. 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 ]
  5. Change in 2-Methylcitric Acid (2-MC ) Levels [ Time Frame: Baseline up to Week 40 ]
  6. Maximum Observed Concentration (Cmax) of human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA-3705 [ Time Frame: 0 (predose) to 336 hours postdose ]
  7. Area Under the Concentration-Time Curve (AUC) of hMUT mRNA-3705 [ Time Frame: 0 (predose) to 336 hours postdose ]
  8. Titer of Anti-Polyethylene Glycol (PEG) Antibodies [ Time Frame: 0 (predose) to 336 hours postdose ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04899310

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Contact: Moderna Clinical Trials Support Center 1-877-777-7187 clinicaltrials@modernatx.com

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United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Emma Raffman       eraffman@mednet.ucla.edu   
Canada, Alberta
Stollery Children's Hospital University of Alberta Recruiting
Edmonton, Alberta, Canada, T6G 2R7
Contact: Cheri Copithorne       cheri.robert@ahs.ca   
Canada, Ontario
Hospital For Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Ashley Wilson       ashley.wilson@sickkids.ca   
Universitair Medisch Centrum Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Contact       S.Michel-2@umcutrecht.nl   
Principal Investigator: Sabine Fuchs         
United Kingdom
Birmingham Children's Hospital NHS Foundation Trust Active, not recruiting
Birmingham, United Kingdom
Royal Manchester Childrens Hospital Recruiting
Manchester, United Kingdom, M13 9WL
Contact: Laura Crowther       genetics.research@mft.nhs.uk   
Sponsors and Collaborators
ModernaTX, Inc.
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Responsible Party: ModernaTX, Inc.
ClinicalTrials.gov Identifier: NCT04899310    
Other Study ID Numbers: mRNA-3705-P101
2020-004980-24 ( EudraCT Number )
First Posted: May 24, 2021    Key Record Dates
Last Update Posted: March 9, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by ModernaTX, Inc.:
Isolated Methylmalonic acidemia
Isolated methylmalonic aciduria
elevated methylmalonic acid (MMA)
Metabolism, Inborn Errors
Genetic Diseases
Additional relevant MeSH terms:
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Amino Acid Metabolism, Inborn Errors
Acid-Base Imbalance
Metabolic Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn