mRNA-3745 for Glycogen Storage Disease
Recruiting in Palo Alto (17 mi)
+15 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: ModernaTX, Inc.
Disqualifiers: Solid organ transplant, Diabetes, others
No Placebo Group
Approved in 2 Jurisdictions
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.12345
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.
See 3 more
Trial 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 (RNA-based Therapy)
Trial OverviewThe 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
2Treatment groups
Experimental Treatment
Group I: SAD: mRNA-3745Experimental Treatment1 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-3745Experimental Treatment1 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Hospital for Sick ChildrenToronto, Canada
Children's Hospital of PhiladelphiaPhiladelphia, PA
Mayo ClinicRochester, MN
Columbia University Medical CenterNew York, NY
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
ModernaTX, Inc.Lead Sponsor
References
[Clinical characteristics and prognosis of infantile-onset glycogen storage disease type II in 16 Chinese patients]. [2022]To explore the clinical characteristics and prognosis of infantile-onset glycogen storage disease type II (GSDII) in Chinese patients.
Allelic heterogeneity of glycogen storage disease type Ib in French patients: a study of 11 cases. [2019]Eleven patients with glycogen storage disease type Ib (GSD Ib) were studied. Using a combination of single-strand conformation polymorphism (SSCP) analysis, restriction enzyme digestion and direct sequencing, we were able to identify 21/22 mutant alleles comprising 12 different mutations in the glucose-6-phosphate translocase gene (G6PT). Among these, one is a novel mutation of G6PT: 855T>C (L229P).
Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIa in Japan. [2019]Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disorder caused by deficiency of the glycogen-debranching enzyme (AGL). Recent studies of the AGL gene have revealed the prevalent mutations in North African Jewish and Caucasian populations, but whether these common mutations are present in other ethnic groups remains unclear. We have investigated eight Japanese GSD IIIa patients from seven families and identified seven mutations, including one splicing mutation (IVS 14+1G-->T) previously reported by us, together with six novel ones: a nonsense mutation (L124X), a splice site mutation (IVS29-1G-->C), a 1-bp deletion (587delC), a 2-bp deletion (4216-4217delAG), a 1-bp insertion (2072-2073insA), and a 3-bp insertion (4735-4736insTAT). The last mutation results in insertion of a tyrosine residue at a putative glycogen-binding site, and the rest are predicted to cause synthesis of truncated proteins lacking the glycogen-binding site at the carboxyl terminal. Thirteen novel polymorphisms have also been revealed in this study: three amino acid substitutions (R387Q, G1115R, and E1343 K), one silent point mutation (L298L), one nucleotide change in the 5'-noncoding region, and eight nucleotide changes in introns. Haplotype analysis with combinations of these polymorphic markers showed L124X, IVS14+1G-->T, and 4216-4217delAG to be on different haplotypes. These results demonstrate the importance of the integrity of the carboxy terminal domain in the AGL protein and the molecular heterogeneity of GSD IIIa in Japan.
Glycogen storage disease type Ib: structural and mutational analysis of the microsomal glucose-6-phosphate transporter gene. [2019]Glycogen storage disease type Ib is caused by a mutation in the gene encoding microsomal glucose-6-phosphate (G6P) transporter. We determined the exon/intron organization of the G6P transporter gene. Four overlapping genomic fragments containing the entire coding region of the gene were amplified by polymerase chain reaction (PCR) using exonic primers, and their nucleotide sequences were determined. The gene spans 4.5 kb and has eight exons. All exon/intron boundaries adhered to the canonical AG/GT rule. We then designed eight pairs of PCR primers to amplify all coding exons for a mutational analysis and studied five Japanese patients with the disease. Two novel homozygous mutations were identified in two families: a three-base deletion (delV235) in exon 2 in a consanguineous family and a splicing mutation (IVS7+1G-->T) in intron 7 in a nonconsanguineous family. Patient 3 was a compound heterozygote of W118R and IVS1+1G-->A, both of which we previously identified [Kure et al., 1998: Biochem Biophys Res Commun 248:426-431]. Patients 4 and 5 were homozygotes of W118R. Including our previous study, we found a total of ten W118R alleles in nine Japanese patients. The results support our previous suggestion that W118R is prevalent among Japanese patients. The genomic sequence data and mutation spectrum obtained from the Japanese patients will facilitate genetic diagnosis of glycogen storage disease type Ib.
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]Glycogen storage disease type 1a (GSD 1a) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). We analyzed the G6Pase gene of two unrelated Japanese families with GSD 1a. DNA sequencing of all five exons and exon-intron junctions revealed a G-to-T transversion at nucleotide 727 (G727T) in exon 5, which has been previously reported to cause abnormal splicing. Family studies using mismatch PCR showed that three patients were homozygous for the G727T mutation, while the parents were heterozygous. To investigate allele frequencies, we screened 216 Japanese healthy volunteers and found one asymptomatic carrier. Our findings suggest that the G727T mutation may be prevalent in Japan.