mRNA-3927 for Propionic Acidemia

Recruiting at 13 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

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to evaluate the long-term safety of mRNA-3927 administered to participants with propionic acidemia (PA) who have previously participated in Study mRNA-3927-P101 (NCT04159103).

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.

How does the drug mRNA-3927 differ from other treatments for propionic acidemia?

mRNA-3927 is unique because it uses messenger RNA (mRNA) technology to address the genetic cause of propionic acidemia by potentially providing the correct instructions to produce functional propionyl-CoA carboxylase, the enzyme deficient in this condition. This approach is different from traditional treatments that mainly focus on managing symptoms rather than targeting the underlying genetic defect. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

[Gene mutation analysis in patients with propionic acidemia]. [2019]

2. Germany 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Transfection screening for defects in the PCCA and PCCB genes encoding propionyl-CoA carboxylase subunits. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Two distinct mutations at the same site in the PCCB gene in propionic acidemia. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Detection of a normally rare transcript in propionic acidemia patients with mRNA destabilizing mutations in the PCCA gene. [2019]