mRNA-3745 for Glycogen Storage Disease

Recruiting at 15 trial locations

Overseen By Moderna WeCare Team

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ModernaTX, Inc.

Disqualifiers: Solid organ transplant, Diabetes, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

45 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called mRNA-3745, which uses messenger RNA to help the body produce a missing protein. It is aimed at adults and children with Glycogen Storage Disease Type Ia (GSD1a). The study will check if the treatment is safe and how well it works.

Will I have to stop taking my current medications?

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

How is the drug mRNA-3745 unique for treating glycogen storage disease?

mRNA-3745 is unique because it uses messenger RNA (mRNA) technology to potentially address the underlying genetic cause of glycogen storage disease, which is different from traditional treatments that may only manage symptoms. This approach aims to provide the body with the instructions to produce the missing or defective proteins needed for proper glycogen metabolism. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults and kids with Glycogen Storage Disease Type 1a (GSD1a). They must have had a low blood sugar event recently and confirmed GSD1a by genetic testing. It's not for those who've had liver transplants, gene therapy for GSD1a, large liver tumors, diabetes, or severe allergies to MRI contrast unless an alternative imaging method is available.

Inclusion Criteria

I have had a low blood sugar event with symptoms.

My GSD1a diagnosis is confirmed by genetic testing.

I haven't been hospitalized for low blood sugar in the last month.

Exclusion Criteria

I have had a solid organ transplant.

I need constant feeding through a tube in my stomach or nose.

My liver tumor grew more than 2 cm or I found more than 5 new tumors in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single Ascending Dose (SAD)

Participants receive a single intravenous (IV) dose of mRNA-3745 in an inpatient setting

1 day

1 visit (inpatient)

Multiple Ascending Dose (MAD)

Participants receive multiple IV doses of mRNA-3745 in an inpatient setting

21 days or more

Multiple visits (inpatient)

Open-label Extension (OLE)

Participants may opt into continuation of treatment to assess long-term safety and clinical activity

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• mRNA-3745

Trial Overview The study tests mRNA-3745 given through the veins to see if it's safe and tolerable for people with GSD1a. The focus is on how participants react to this new treatment over time.

Participant Groups

Group I: SAD: mRNA-3745 Experimental Treatment 1 Intervention

Participants will receive a single intravenous (IV) dose of mRNA-3745 on Day 1 in an inpatient setting. Participants that are/have been enrolled in the study and receive an administration of mRNA-3745 may also enroll in one of the MAD cohorts. The first MAD dose must occur at least 21 days after the SAD dose.

Group II: MAD: mRNA-3745 Experimental Treatment 1 Intervention

Participants will receive multiple IV doses of mRNA-3745 in an inpatient setting. Participants will have the option to continue treatment in the OLE.

mRNA-3745 is already approved in European Union, United States for the following indications:

Approved in European Union as mRNA-3745 for:

• Glycogen storage disease type 1a (GSD1a)

Approved in United States as mRNA-3745 for:

• Glycogen storage disease type 1a (GSD1a)

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

Infantile-onset glycogen storage disease type II (GSDII) in Chinese patients is characterized by severe symptoms such as cardiac hypertrophy, muscular weakness, and hypotonia, with a high mortality rate; 14 out of 16 patients died by a median age of 9 months.

The diagnosis of GSDII can be effectively confirmed by measuring acidic α-glucosidase activity in peripheral blood, which was found to be remarkably low or absent in all patients studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical characteristics and prognosis of infantile-onset glycogen storage disease type II in 16 Chinese patients]. Fu, LJ., Chen, SB., Qiu, WJ., et al.[2022]

In a study of 11 patients with glycogen storage disease type Ib (GSD Ib), researchers identified 21 out of 22 mutant alleles in the glucose-6-phosphate translocase gene (G6PT), which is crucial for understanding the genetic basis of the disease.

Among the identified mutations, one was a novel mutation (855T>C, L229P), highlighting the potential for new insights into the genetic diversity of GSD Ib and its implications for diagnosis and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allelic heterogeneity of glycogen storage disease type Ib in French patients: a study of 11 cases. Trioche, P., Petit, F., Francoual, J., et al.[2019]

In a study of eight Japanese patients with Glycogen storage disease type IIIa (GSD IIIa), seven mutations were identified, including six novel mutations that affect the glycogen-debranching enzyme (AGL), highlighting the genetic diversity of this condition in different populations.

The identified mutations are predicted to disrupt the function of the AGL protein, particularly affecting its glycogen-binding site, which is crucial for its role in glycogen metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIa in Japan. Okubo, M., Horinishi, A., Takeuchi, M., et al.[2019]

The study identified the complete structure of the G6P transporter gene, which is crucial for understanding glycogen storage disease type Ib, and confirmed it consists of eight exons and spans 4.5 kb.

In a mutational analysis of five Japanese patients, two novel mutations were discovered, including a three-base deletion and a splicing mutation, highlighting the genetic diversity of the disease and aiding in future genetic diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycogen storage disease type Ib: structural and mutational analysis of the microsomal glucose-6-phosphate transporter gene. Hou, DC., Kure, S., Suzuki, Y., et al.[2019]

The study identified a specific mutation (G727T) in the G6Pase gene associated with glycogen storage disease type 1a (GSD 1a) in two unrelated Japanese families, indicating a genetic cause for the disorder.

Among 216 healthy Japanese volunteers screened, only one was found to be an asymptomatic carrier of the G727T mutation, suggesting that while the mutation may be prevalent, it does not affect all carriers, highlighting the importance of genetic screening in understanding GSD 1a.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of a point mutation (G727T) in the glucose-6-phosphatase gene in Japanese patients with glycogen storage disease type 1a, and carrier screening in healthy volunteers. Okubo, M., Aoyama, Y., Kishimoto, M., et al.[2019]

References

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

[Clinical characteristics and prognosis of infantile-onset glycogen storage disease type II in 16 Chinese patients]. [2022]

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

Allelic heterogeneity of glycogen storage disease type Ib in French patients: a study of 11 cases. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIa in Japan. [2019]

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

Glycogen storage disease type Ib: structural and mutational analysis of the microsomal glucose-6-phosphate transporter gene. [2019]

5. Denmark pubmed.ncbi.nlm.nih.gov

Identification of a point mutation (G727T) in the glucose-6-phosphatase gene in Japanese patients with glycogen storage disease type 1a, and carrier screening in healthy volunteers. [2019]