A Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia

NCT ID: NCT04899310

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

74 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-06

Study Completion Date

2028-07-01

Brief Summary

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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, efficacy, pharmacokinetics, and pharmacodynamics of intravenously (IV)-infused mRNA-3705.

Detailed Description

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This study comprises 3 parts and is designed to evaluate multiple doses and dosing intervals of mRNA-3705.

Parts 1 and 3 are designed to characterize the safety, tolerability, and pharmacological activity of mRNA-3705 administered via intravenous infusion to participants with isolated MMA due to MUT deficiency. Part 2 will evaluate the efficacy of mRNA-3705 as assessed by the change in plasma methylmalonic acid levels.

Participants who complete the treatment period in any part of the study, including the end of treatment (EOT) visit, will be offered participation in the mRNA-extension study (mRNA-3705-P101-EXT; NCT05295433) or may transition to the follow-up period of the study. All participants, including those randomized to placebo in Part 2, will receive mRNA-3705 in the extension study.

Conditions

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Methylmalonic Acidemia

Keywords

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Isolated Methylmalonic Acidemia Isolated Methylmalonic Aciduria Elevated Methylmalonic Acid (MMA) Metabolism, Inborn Errors Genetic Diseases Moderna mRNA mRNA-3705

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parts 2 and 3 run in parallel and occur after Part 1.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Parts 1 and 3 are open label and non-randomized. Part 2 is blinded and randomized.

Study Groups

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mRNA-3705

Participants in Part 1 will receive a weight-based dose of mRNA-3705, administered IV, once every 2 weeks or once every 3 weeks for up to 10 doses over approximately 40 weeks. Participants in Part 2 and Part 3 will receive mRNA-3705 at the selected dose level and frequency for 3 months.

Group Type EXPERIMENTAL

mRNA-3705

Intervention Type BIOLOGICAL

Sterile liquid for infusion

Placebo

Participants only in Part 2 will receive placebo at the selected frequency for 3 months.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Sterile liquid for infusion

Interventions

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mRNA-3705

Sterile liquid for infusion

Intervention Type BIOLOGICAL

Placebo

Sterile liquid for infusion

Intervention Type BIOLOGICAL

Other Intervention Names

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modified mRNA encoding human methylmalonyl-coenzyme A mutase

Eligibility Criteria

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Inclusion Criteria

* (Part 1 only) Participant has a body weight of ≥11.0 kilograms at the screening visit.
* Participant has a diagnosis of isolated MMA due to MUT deficiency confirmed by molecular genetic testing.
* Participant has a blood vitamin B12 level equal to or above the lower limit of normal (based on laboratory reference range) confirmed in the screening period.
* Participant or their legally authorized representative is willing and able to provide informed consent and/or assent as mandated by local regulations and is willing and able to comply with study-related assessments.
* Sexually active participants of childbearing or reproductive potential agree to use a highly effective method of contraception, consistent with local regulations, during the study and for 3 months after the last administration of study drug.
* (Part 2 only) Participants with 2 screening MMA levels ≥400 micromolar.
* (Parts 2 and 3 only) Participant is ≥5 years of age at the time of informed consent/assent.

Exclusion Criteria

* Participant has a diagnosis of isolated MMA cofactor adenosyl-cobalamin (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 or planned organ transplantation during the period of study participation.
* 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.
* (Part 2 only) Participant has the partial MUT deficiency disease phenotype, as assessed by genotyping, clinical phenotype/presentation, or vitamin B12-responsive MMA.
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ModernaTX, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UCLA Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Lucile Packard Children's Hospital at Stanford

Palo Alto, California, United States

Site Status RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Children's Hospital at Westmead

Westmead, New South Wales, Australia

Site Status WITHDRAWN

Royal Children's Hospital Melbourne

Parkville, Victoria, Australia

Site Status WITHDRAWN

Stollery Children's Hospital University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

Hospital For Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

Hôpital Necker - Enfants Malades

Paris, , France

Site Status RECRUITING

Erasmus MC

Rotterdam, , Netherlands

Site Status RECRUITING

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Site Status RECRUITING

Hospital Sant Joan de Deu - PIN

Esplugues de Llobregat, Barcelona, Spain

Site Status RECRUITING

Hospital Universitario Cruces

Barakaldo, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

CHUS - H. Clinico U. de Santiago

Santiago de Compostela, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocio - PPDS

Seville, , Spain

Site Status RECRUITING

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, , United Kingdom

Site Status TERMINATED

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada France Netherlands Spain United Kingdom

Central Contacts

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Moderna WeCare Team

Role: CONTACT

Phone: 1-866-663-3762

Email: [email protected]

Facility Contacts

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Campos Monserrath

Role: primary

Thu Quan

Role: primary

Rebecca Madden

Role: primary

Cheri Copithorne

Role: primary

Dhillon Preet

Role: primary

Michaela Semeraro

Role: primary

Role: primary

Role: primary

Isabel Maria Miquel Aymar

Role: primary

Martin Rodriguez Ohiane

Role: primary

Ianire Gallego Amaro

Role: primary

Laura Lopez Valverde

Role: primary

Ana Muñoz

Role: primary

Laura Crowther

Role: primary

Other Identifiers

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2022-502492-32-00

Identifier Type: OTHER

Identifier Source: secondary_id

mRNA-3705-P101

Identifier Type: -

Identifier Source: org_study_id