NCT03810690

Open Label Study of mRNA-3704 in Patients With Isolated Methylmalonic Acidemia

Withdrawn Phase 1, PHASE2 Last updated 13 November 2020

What this trial tests

Phase 1, PHASE2 trial testing mRNA-3704 in Methylmalonic Acidemia (MMA). Withdrawn.

Timeline

28 May 2019

Primary endpoint
18 August 2020

18 August 2020

Quick facts

Lead sponsor	ModernaTX, Inc.
Phase	Phase 1, PHASE2
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Start date	28 May 2019
Primary completion	18 August 2020
Estimated completion	18 August 2020

Drugs / interventions tested

• mRNA-3704 — full drug profile →

Conditions studied

• Methylmalonic Acidemia (MMA) — all drugs for Methylmalonic Acidemia (MMA) →
• Metabolism, Inborn Errors — all drugs for Metabolism, Inborn Errors →

Sponsor

ModernaTX, Inc. — full company profile →

Who can join

1 and older, any sex, with Methylmalonic Acidemia (MMA) or Metabolism, Inborn Errors. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This First-in-Human (FIH) Phase 1/2 study will evaluate mRNA-3704 in patients with methylmalonic acidemia/aciduria (MMA) due to methylmalonyl-coenzyme A mutase (MUT) deficiency between 1 to 18 years of age with elevated plasma methylmalonic acid. The study is designed to characterize baseline biomarker levels followed by assessment of safety, pharmacokinetics, and pharmacodynamics of different doses of mRNA-3704 in patients affected by MMA as part of the Dose Escalation phase.

During the Dose Escalation phase, three dose levels of mRNA-3704 are planned to be investigated in this study among patients with MMA due to MUT deficiency: low dose, mid dose, and high dose. An additional cohort to evaluate a fourth dose level may be considered jointly by the independent SMC and the Sponsor.

Upon establishment of a dose with acceptable safety and pharmacodynamic activity, additional patients will be enrolled in a Dose Expansion phase to allow for further characterization of the safety and pharmacodynamics of mRNA-3704.

Patients in both phases of study will participate in a pre-dosing observational period, followed by a treatment period, and then a follow-up period after withdrawal of treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Lipid nanoparticles for mRNA delivery.
   Hou X, Zaks T, Langer R, Dong Y. · · 2021 · cited 2524× · PMID 34394960 · DOI 10.1038/s41578-021-00358-0
2. Lipids and Lipid Derivatives for RNA Delivery.
   Zhang Y, Sun C, Wang C, Jankovic KE, et al · · 2021 · cited 423× · PMID 34279087 · DOI 10.1021/acs.chemrev.1c00244
3. Opportunities and Challenges in the Delivery of mRNA-based Vaccines.
   Wadhwa A, Aljabbari A, Lokras A, Foged C, et al · · 2020 · cited 410× · PMID 32013049 · DOI 10.3390/pharmaceutics12020102
4. RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.
   Yu AM, Choi YH, Tu MJ. · · 2020 · cited 271× · PMID 32929000 · DOI 10.1124/pr.120.019554
5. Paving the Road for RNA Therapeutics.
   Dammes N, Peer D. · · 2020 · cited 159× · PMID 32893005 · DOI 10.1016/j.tips.2020.08.004
6. Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives.
   Gómez-Aguado I, Rodríguez-Castejón J, Vicente-Pascual M, Rodríguez-Gascón A, et al · · 2020 · cited 144× · PMID 32093140 · DOI 10.3390/nano10020364
7. Non-coding RNAs in human health and disease: potential function as biomarkers and therapeutic targets.
   Loganathan T, Doss C GP. · · 2023 · cited 133× · PMID 36625940 · DOI 10.1007/s10142-022-00947-4
8. Current Advances in RNA Therapeutics for Human Diseases.
   Zogg H, Singh R, Ro S. · · 2022 · cited 117× · PMID 35269876 · DOI 10.3390/ijms23052736