mRNA-3927 for Propionic Acidemia

Recruiting at 15 trial locations

Overseen By Moderna WeCare Team

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ModernaTX, Inc.

Disqualifiers: Liver transplant, Kidney transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the long-term safety of mRNA-3927 for individuals with propionic acidemia (PA), a rare genetic metabolic disorder. The study involves participants from a previous trial who have already begun receiving mRNA-3927. Eligible participants are those who completed the earlier study and are prepared to continue treatment. The trial aims to ensure the treatment's safety for ongoing use. As a Phase 1, Phase 2 trial, it seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that mRNA-3927 is likely to be safe for humans?

Research has shown that mRNA-3927 was tested for safety in earlier studies, which suggest that participants generally tolerated it well. The treatment successfully reached liver cells, indicating it targets the intended area effectively.

Regarding side effects, the data does not reveal any major safety concerns. However, since the treatment remains in early testing stages, monitoring for side effects is crucial. These studies focused on safety and tolerability, assessing how well participants handle the treatment and any side effects.

Researchers closely monitor participants to ensure safety, adjusting doses if necessary to minimize risks. Prospective trial participants should consider these factors and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Propionic Acidemia, which often involve dietary management and liver transplant, mRNA-3927 uses a cutting-edge approach by leveraging messenger RNA technology. This treatment works by delivering synthetic mRNA into cells, enabling them to produce the necessary enzymes that patients with Propionic Acidemia lack. Researchers are excited about mRNA-3927 because it targets the root cause of the condition at a molecular level, potentially offering a more direct and effective treatment compared to current options.

What evidence suggests that mRNA-3927 might be an effective treatment for propionic acidemia?

Research has shown that mRNA-3927, the investigational treatment in this trial, may help treat propionic acidemia (PA). Studies have found that this treatment can reach liver cells and aid in producing the enzyme that people with PA lack. Early data suggest that patients using mRNA-3927 experienced fewer metabolic decompensation events (MDEs), episodes when the body struggles to break down certain fats and proteins. This decrease in MDEs indicates the treatment's potential effectiveness. The results so far are promising, suggesting possible benefits for people with PA. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with propionic acidemia who were previously in the mRNA-3927-P101 study. They must have completed that study's end-of-treatment visit within 10 days of starting this one. People can't join if they've had a liver or kidney transplant, aren't expected to benefit from more treatment, or have health issues that make it risky.

Inclusion Criteria

Completed the EOT Visit in Study mRNA-3927-P101 within 10 days of first dose of mRNA-3927 in current study.

Participated in Study mRNA-3927-P101.

Exclusion Criteria

I have had a liver or kidney transplant.

Not expected to receive clinical benefit from continued mRNA-3927 administration, in the opinion of the Investigator.

Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the individual at increased risk by participating in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Treatment

Participants receive mRNA-3927 at the same dose and interval as in the previous study

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• mRNA-3927

Trial Overview The trial is testing the long-term safety and effectiveness of a drug called mRNA-3927 in patients with propionic acidemia who took part in an earlier phase of research. It continues where the previous study left off.

How Is the Trial Designed?

Group I: mRNA-3927 Experimental Treatment 1 Intervention

Participants will receive the applicable dose identified during Study mRNA-3927-P101 (NCT04159103) on Day 1. The dose can be adjusted based on Sponsor recommendation.

Who Is Running the Clinical Trial?

ModernaTX, Inc.

Lead Sponsor

Trials

127

Recruited

66,790,000+

Dr. Stephen Hoge

ModernaTX, Inc.

Chief Medical Officer

MD from Harvard Medical School

Stéphane Bancel

ModernaTX, Inc.

Chief Executive Officer since 2011

MBA from Harvard Business School, MSc in Engineering from École Centrale Paris

Published Research Related to This Trial

A new method has been developed to identify defective genes causing propionic acidemia by using lipid-mediated transient transfection of normal PCCA or PCCB genes into primary fibroblasts.

This approach allows for reliable identification of the specific gene mutation responsible for the enzyme defect, aiding in the mutational analysis of propionyl-CoA carboxylase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transfection screening for defects in the PCCA and PCCB genes encoding propionyl-CoA carboxylase subunits. Rodriguez-Pombo, P., Pérez-Cerdá, C., Desviat, LR., et al.[2019]

In patients with propionic acidemia, mutations in the PCCA gene lead to the production of an abnormal mRNA transcript with an 84 bp insertion, which results in translation termination and reduced levels of the normal protein.

The study suggests that screening for this 84 bp insertion using RT-PCR could serve as a rapid diagnostic tool for identifying RNA destabilizing mutations, highlighting the complexity of interpreting mRNA species in genetic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of a normally rare transcript in propionic acidemia patients with mRNA destabilizing mutations in the PCCA gene. Campeau, E., Dupuis, L., Leclerc, D., et al.[2019]

In a study of 11 Chinese patients with propionic acidemia, researchers identified 13 mutations in the PCCA and PCCB genes, including 10 novel mutations, which contribute to the disease's genetic diversity.

The study found no predominant mutation among the patients, indicating a varied mutation spectrum in the Chinese population affected by propionic acidemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Gene mutation analysis in patients with propionic acidemia]. Hu, YH., Han, LS., Ye, J., et al.[2019]

A study screening over 130,000 Japanese newborns revealed that the frequency of propionic acidemia is more than ten times higher than previously reported, with many patients exhibiting milder symptoms than the severe form typically associated with the condition.

The research identified a common mutation (Y435C) in the PCCB gene among patients with milder phenotypes, highlighting the importance of recognizing these patients to understand their natural history and the diverse effects of PCCB mutations, including unusual patterns of exon skipping and mRNA absence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unexpectedly high prevalence of the mild form of propionic acidemia in Japan: presence of a common mutation and possible clinical implications. Yorifuji, T., Kawai, M., Muroi, J., et al.[2022]

Two mutations in the PCCB gene were identified in a patient with propionic acidemia, highlighting the genetic complexity of this metabolic disorder.

One mutation caused a deletion of an isoleucine residue, while the other resulted in a frameshift and a premature stop codon, indicating that both mutations significantly impair the function of the propionyl-CoA carboxylase enzyme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two distinct mutations at the same site in the PCCB gene in propionic acidemia. Lamhonwah, AM., Troxel, CE., Schuster, S., et al.[2019]

Citations

1. nature.com nature.com/articles/s41586-024-07266-7

Interim analyses of a first-in-human phase 1/2 mRNA trial ... Together with reductions in MDEs, these data suggest that IV infusion of mRNA-3927 resulted in successful transportation into liver cells, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04159103

NCT04159103 | Open-Label Study of mRNA-3927 in ... This 3-part, Phase 1/2 study is designed to characterize the safety, tolerability, and pharmacological activity (as assessed by biomarker measurements) and ...

3. ddw-online.com ddw-online.com/positive-initial-data-on-first-mrna-therapy-for-propionic-acidemia-23770-202305/

Positive initial data on first mRNA therapy for propionic ... Moderna has reported encouraging interim data from its Phase I/II trial of mRNA-3927, an mRNA therapy for rare metabolic disorder propionic acidemia (PA).

4. s29.q4cdn.com s29.q4cdn.com/435878511/files/doc_downloads/program_detail/2024/06/pa-5-2-24.pdf

Propionic acidemia (PA) (mRNA-3927) - Moderna Presentation • Results show encouraging early signs of potential clinical benefit with mRNA-3927. – Reductions in the number of metabolic decompensation ...

5. genengnews.com genengnews.com/topics/translational-medicine/moderna-reports-phase-i-ii-data-for-propionic-acidemia-mrna-therapy/

Moderna Reports Phase I/II Data for Propionic Acidemia ... The findings indicate that intravenous infusion of mRNA-3927 resulted in successful transport into liver cells and the synthesis of an active ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-mrna-3927-for-patients-with-propionic-acidemia/

Study on the Safety and Effectiveness of mRNA-3927 for ... This study investigates the safety and effectiveness of the gene therapy mRNA-3927 for the treatment of the rare genetic condition, Propionic Acidemia.

7. mountsinai.org mountsinai.org/clinical-trials/open-label-study-of-mrna-3927-in-participants-with-propionic-acidemia

Open-Label Study of mRNA-3927 in Participants ... Summary: This First-in-Human (FIH) Phase 1/2 study is designed to characterize the safety, tolerability, and pharmacological activity (as assessed by ...