D-galactose for Congenital Disorder of Glycosylation

(AVTX-801 Trial)

Overseen By Mary Freeman, MS, CGC

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Eva Morava-Kozicz

Must be taking: D-galactose

Disqualifiers: Aldolase B deficiency, Galactosemia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

8 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a clinical trial to evaluate the efficacy of AVTX-801 (D-galactose) on the clinical manifestations of PGM1-CDG in participants currently taking D-galactose.

Will I have to stop taking my current medications?

The trial requires participants to be on a stable dose of D-galactose therapy, so you will not need to stop taking D-galactose. The protocol does not specify about other medications.

What data supports the effectiveness of the drug AVTX-801 for treating Congenital Disorder of Glycosylation?

Some studies have shown that D-galactose, a component of AVTX-801, led to clinical improvements in patients with certain types of congenital disorders of glycosylation, like PGM1-CDG, by improving glycosylation (a process important for cell function). However, in a small trial for PMM2-CDG, while some milder cases showed positive changes, overall significant improvement was not observed, indicating more research is needed. ^{1 2 3 4 5}

Is D-galactose safe for use in humans?

In a pilot study with patients having PGM1-CDG, oral D-galactose supplementation was found to be safe, with no adverse effects reported. Laboratory tests showed improvements in liver function and other health markers, suggesting it is generally safe for human use. ^{1 4 6 7 8}

How does the drug AVTX-801 differ from other treatments for Congenital Disorder of Glycosylation?

AVTX-801, which involves D-galactose supplementation, is unique because it targets the underlying glycosylation process in PMM2-CDG, a specific type of Congenital Disorder of Glycosylation, rather than just addressing symptoms. While current treatments are mainly symptomatic, D-galactose aims to improve glycosylation, although more research is needed to confirm its effectiveness. ^{1 9 10 11 12}

Research Team

Eva Morava-Kozicz, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Adults aged 18-60 with PGM1-CDG who are already on a stable D-galactose therapy can join. They must understand the study and agree to use effective birth control if necessary. People with certain metabolic disorders, liver failure, recent other trial participation, or severe reactions to galactose cannot participate.

Inclusion Criteria

I am on a consistent dose of D-galactose therapy.

Subject/legally authorized representative (LAR) is able to understand and provide written informed consent, and assent (as applicable) to participate in this study.

I am between 18 and 60 years old.

Exclusion Criteria

In the site Principal Investigator's opinion, subject has a history of galactose intolerance that precludes the subject from participation in this study.

I have a rare blood or metabolic disorder.

According to the main doctor at the research site, you have had serious side effects from taking galactose by mouth, such as severe diarrhea, severe and frequent vomiting, constipation, galactose in your urine, or increased storage of sugar in your liver.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-In

Participants continue D-galactose therapy and are monitored for hypoglycemic events to establish a baseline rate

4 weeks

Treatment Period 1

Participants receive either AVTX-801 or placebo for 18 weeks

18 weeks

Open Label Recovery

Participants receive commercially available D-galactose for 18 weeks between treatment periods

18 weeks

Treatment Period 2

Participants receive the alternate treatment (AVTX-801 or placebo) for 18 weeks

18 weeks

Long-term Open-label Safety Follow-up

Participants enter a long-term safety follow-up period with AVTX-801

12 months

Treatment Details

Interventions

• AVTX-801

Trial Overview The study is testing AVTX-801 for people with PGM1-CDG who take D-galactose. It aims to find the best dose and assess long-term safety of this treatment in adults currently using D-galactose.

Participant Groups

Group I: Placebo, then AVTX-801 Experimental Treatment 2 Interventions

Participants receive placebo (in applesauce) during Treatment Period 1 and then AVTX-801 1.5g/kg/day (in applesauce) during Treatment Period 2.

Group II: AVTX-801, then Placebo Experimental Treatment 2 Interventions

Participants receive AVTX-801 1.5g/kg/day (in applesauce) during Treatment Period 1 and then placebo (in applesauce) during Treatment Period 2.

Who Is Running the Clinical Trial?

Eva Morava-Kozicz

Lead Sponsor

Trials

4

Recruited

80+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

References

1. England pubmed.ncbi.nlm.nih.gov

D-galactose supplementation in individuals with PMM2-CDG: results of a multicenter, open label, prospective pilot clinical trial. [2022]

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

Nine years of newborn screening for classical galactosemia in the Netherlands: Effectiveness of screening methods, and identification of patients with previously unreported phenotypes. [2018]

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

The Galactose Index measured in fibroblasts of GALT deficient patients distinguishes variant patients detected by newborn screening from patients with classical phenotypes. [2020]

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

Oral D-galactose supplementation in PGM1-CDG. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Current and Future Treatments for Classic Galactosemia. [2021]

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

Gastrointestinal Health in Classic Galactosemia. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Qualitative interviews with adults with Classic Galactosemia and their caregivers: disease burden and challenges with daily living. [2022]

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

Effects of temporary low-dose galactose supplements in children aged 5-12 y with classical galactosemia: a pilot study. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Liquid chromatography-tandem mass spectrometry enzyme assay for UDP-galactose 4'-epimerase: use of fragment intensity ratio in differentiation of structural isomers. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Validation of an automated ultraperformance liquid chromatography IgG N-glycan analytical method applicable to classical galactosaemia. [2019]

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

Affinity purification of human alpha galactosidase utilizing a novel small molecule biomimetic of alpha-D-galactose. [2021]

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

N-glycan abnormalities in children with galactosemia. [2014]