What side effects are associated with this type of intervention?

Gene therapy for Glycogen Storage Disease, such as the DTX401 trial, aims to correct the underlying genetic defect to improve glucose metabolism. Common side effects of gene therapy can include immune reactions to the viral vector used for gene delivery, which may manifest as fever, chills, or flu-like symptoms. There is also a risk of liver enzyme elevations, which necessitates regular monitoring of liver function. Other potential side effects include injection site reactions and, in rare cases, more severe immune responses or unintended effects on other genes.

What prior FDA approvals exist?

There are no specific mentions of prior FDA approvals for gene therapies like DTX401 for Glycogen Storage Disease in the provided context. However, enzyme replacement therapy has been developed for related conditions such as Pompe disease, which involves the use of recombinant human enzymes to address enzyme deficiencies. This indicates a broader trend towards using advanced biotechnological approaches, including gene and enzyme replacement therapies, to treat metabolic disorders.

What other types of research exist?

Promising novel alternatives to DTX401 for Glycogen Storage Disease patients may include other gene therapies, RNA silencing techniques, and CRISPR-Cas9 gene editing. These advanced treatments are being explored for various metabolic and genetic disorders and could potentially be adapted for GSD treatment.

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Gene Therapy

Gene Therapy for Glycogen Storage Disease Type Ia

Phase 3

Recruiting

Research Sponsored by Ultragenyx Pharmaceutical Inc

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Currently receiving a therapeutic regimen of cornstarch (or equivalent), following international guidance/recommendations with stable nutrition, glycemic, and clinical status

Females of childbearing potential and fertile males must consent to use highly effective contraception from the period following informed consent through the duration of the 144-week study and in cases of early withdrawal at least 48 weeks after the last dose of investigational product (IP). Female subjects must agree not to become pregnant. Male subjects must agree not to father a child or donate sperm

Must not have

History of liver transplant, including hepatocyte cell therapy/transplant

History of liver disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

Summary

This trial tests DTX401, a treatment to help people with a genetic condition called GSDIa manage their blood sugar levels better. It targets patients aged 8 and older who struggle to maintain normal blood sugar. The treatment aims to reduce the need for extra glucose by helping the body control blood sugar more effectively.

Who is the study for?

This trial is for individuals with Glycogen Storage Disease Type Ia (GSDIa) who are on a stable regimen of cornstarch therapy. They must be willing to use effective contraception and not plan pregnancy. Excluded are those with liver disease, previous gene therapies, detectable AAV8 antibodies, or certain lab abnormalities.

What is being tested?

The study tests DTX401's ability to reduce reliance on glucose replacement in GSDIa patients versus placebo. It aims to improve glucose control quality over a period of 144 weeks, comparing the effects of an oral corticosteroid treatment against a placebo.

What are the potential side effects?

Potential side effects may include immune reactions to the viral vector used for gene transfer (AAV8), changes in liver function tests, and typical risks associated with corticosteroids such as increased blood sugar levels and susceptibility to infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am on a stable cornstarch-based treatment plan for my condition.

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I agree to use effective birth control during and after the study for the specified times.

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My GSDIa diagnosis was confirmed by genetic testing or liver biopsy.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a liver transplant or received liver cell therapy.

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I have a history of liver disease.

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I have a liver tumor larger than 5 cm.

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My liver tests show inflammation or I have cirrhosis.

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I have a liver tumor between 3 and 5 cm that's growing quickly.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2021 Phase 1 & 2 trial • 12 Patients • NCT03517085

100%

Headache

67%

Arthralgia

67%

Libido Increased

67%

Liver Function Test Increased

67%

Muscle Spasms

33%

Metabolic Disorder

33%

Hepatic Enzyme Increased

33%

Blood Creatine Phosphokinase Increased

33%

Cough

33%

Arthropod Bite

33%

Gastrointestinal Disorder

33%

Upper Respiratory Tract Congestion

33%

Dehydration

33%

Migraine

33%

Plantar Fasciitis

33%

Abdominal Wall Infection

33%

Diarrhoea

33%

Chills

33%

Pyrexia

33%

Thirst

33%

Nasopharyngitis

33%

Upper Respiratory Tract Infection

33%

Anxiety

33%

Nephrolithiasis

33%

Oropharyngeal Pain

33%

Rash

33%

Gastrointestinal Viral Infection

33%

Infection

33%

Sinobronchitis

33%

Sinusitis

33%

Hypertriglyceridaemia

33%

Hypoglycaemia

33%

Nausea

33%

Vomiting

33%

Gastroenteritis

33%

Hair Growth Abnormal

100%

80%

60%

40%

20%

Study treatment Arm

DTX401 Cohort 1

DTX401 Cohort 2

DTX401 Cohort 3

DTX401 Cohort 4

Total

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: DTX401, Then PlaceboExperimental Treatment4 Interventions

Participants receive single peripheral intravenous (IV) infusion of DTX401 in solution. At week 48 participants receive single peripheral IV infusion of Placebo.

Group II: DTX401 (Japan Only)Experimental Treatment2 Interventions

Participants receive single peripheral intravenous (IV)infusion of DTX401 in solution.

Group III: Placebo, Then DTX401Placebo Group4 Interventions

Participants receive single peripheral IV infusion of Placebo. At week 48 eligible participants receive single peripheral IV infusion of DTX401 solution.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

DTX401

2018

Completed Phase 2

~20

Oral corticosteroids

2005

Completed Phase 3

~2070

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Glycogen Storage Disease (GSD) aim to manage blood glucose levels and prevent hypoglycemia. Traditional treatments include frequent feedings of cornstarch or glucose to maintain euglycemia. Gene therapy, such as DTX401, represents a novel approach by introducing a functional copy of the glucose-6-phosphatase gene using an adeno-associated virus (AAV) vector. This therapy aims to restore normal glucose metabolism, potentially reducing or eliminating the need for exogenous glucose replacement. For GSD patients, this could significantly improve quality of life by stabilizing blood glucose levels and reducing the burden of constant dietary management.