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

PHASE1PHASE2RECRUITING

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.

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Study details:

This study comprises 2 parts: Dose Optimization part (Part 1) followed by a Dose Expansion part (Part 2). The study is designed to evaluate multiple doses and dosing intervals of mRNA-3705. In both parts, after confirmation of eligibility, participants will enter an Observation Period (48 to 72 hours pre-dose) in Part 1 and 24 hours before dose 1 in Part 2), followed by the Treatment Period.

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 follow-up part of the study (approximately 2-year follow-up in Part 1 and 6-months follow-up in Part 2).

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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 blood 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 blood 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 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 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.

(Part 2 only) At least 1 documented MDE in the 12-month period before consent.

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 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) History of hepatitis B (known positive hepatitis B surface antigen [HbsAg]), hepatitis C virus (HCV), or HIV (positive HIV1/HIV-2 antibodies). Participants with a past or resolved hepatitis virus B (HBV) infection (defined as the presence of hepatitis B core antibody and absence of HbsAg) are eligible. Participants with history of positive results for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

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Eligibility

Age eligible for study : 1 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2021-08-06

Primary completion: 2026-08-01

Study completion finish: 2028-08-01

Study type

TREATMENT

Phase

PHASE1

PHASE2

Trial ID

NCT04899310

Intervention or treatment

BIOLOGICAL: mRNA-3705

Conditions

• Methylmalonic Acidemia

Condition: Methylmalonic Acidemia
BIOLOGICAL: mRNA-3705
Westmead, New South Wales, Australia and more
Sponsor: ModernaTX, Inc.

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Children's Hospital at Westmead

Research sites nearby

Select from list below to view details:

Children's Hospital at Westmead
Westmead, New South Wales, Australia
Royal Children's Hospital Melbourne
Parkville, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: mRNA-3705 Participants in Part 1 will receive a weight based dose of mRNA-3705, administered intravenously (IV), once every 2 weeks (Q2W) or once every 3 weeks (Q3W) for up to 10 doses over approximately 40 weeks. Participants in Part 2 will receive mRNA 3705 at the selected dose level and frequency for up to 12 months.	BIOLOGICAL: mRNA-3705 A sterile liquid for injection

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Part 1: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Study Drug-related TEAES, Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation	Not Specified	Up to 144 weeks
Part 2: Annualized Frequency of Metabolic Decompensation Events (MDEs)	Not Specified	Baseline up to Week 52

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Change in Blood Methylmalonic Acid Level	Not Specified	Baseline up to Week 40
Maximum Observed Effect (Emax) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705	Not Specified	Baseline up to Week 40
Area Under the Effect Curve (AUEC) for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705	Not Specified	Baseline up to Week 40
Duration of Response for Plasma Methylmalonic Acid Measurement after Single and Repeated Administrations of mRNA-3705	Not Specified	0 (predose) up to 336 hours postdose
Change in Blood 2-Methylcitric Acid (2-MC ) Levels	Not Specified	Baseline up to Week 40
Maximum Observed Concentration (Cmax) of human Methylmalonyl-Coenzyme A Mutase (hMUT) mRNA-3705	Not Specified	0 (predose) to 336 hours postdose
Area Under the Concentration-Time Curve (AUC) of hMUT mRNA-3705	Not Specified	0 (predose) to 336 hours postdose
Titer of Anti-Polyethylene Glycol (PEG) Antibodies	Not Specified	0 (predose) to 336 hours postdose

Frequently Asked Questions

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References

Clinical Trials Gov: A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of mRNA-3705 in Participants With Isolated Methylmalonic Acidemia