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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called AVTX-801 for individuals with PGM1-CDG, a rare genetic condition affecting sugar processing in the body. The goal is to determine if AVTX-801 improves symptoms more effectively than a placebo. Participants will alternate between the actual treatment and a placebo to compare effects. Suitable candidates have PGM1-CDG and are already taking D-galactose regularly. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that D-galactose, the main ingredient in AVTX-801, has been safely used in patients with PGM1-CDG, a specific genetic disorder. In an initial study, patients who took D-galactose orally reported no side effects, indicating good tolerance. Although this study involved only a small number of participants, the results are encouraging for those considering joining a trial with AVTX-801. Always consult a healthcare provider for personal advice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PGM1-CDG?

Unlike the standard treatments for Congenital Disorder of Glycosylation, which often focus on managing symptoms, AVTX-801 is unique because it directly targets the underlying issues in glycosylation. This treatment introduces D-galactose, a simple sugar, to potentially correct the glycosylation process itself. Researchers are excited about AVTX-801 because it could address the root cause of the disorder, offering a more direct and potentially transformative approach rather than just alleviating symptoms. Plus, the delivery method—mixing the treatment in applesauce—could make it easier and more pleasant for patients, especially children, to take regularly.

What evidence suggests that AVTX-801 could be an effective treatment for PGM1-CDG?

Research has shown that D-galactose, the main ingredient in AVTX-801, may help treat certain genetic disorders affecting sugar processing in the body, known as congenital disorders of glycosylation (CDG). In an initial study, patients with a specific type of CDG called PGM1-CDG took D-galactose orally and did not experience any negative side effects, indicating its safety. D-galactose has also been used successfully to treat another type of CDG, PMM2-CDG, with positive results. These findings suggest that AVTX-801, which participants in this trial will receive in different sequences with a placebo, might help improve symptoms in people with PGM1-CDG. ^{1 2 3 4 6}

Who Is on the Research Team?

Eva Morava-Kozicz, MD, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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 have been diagnosed with PGM1-CDG through genetic testing.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. withpower.com withpower.com/trial/phase-2-and-3-pgm1-cdg---phosphoglucomutase-1-related-congenital-disorder-of-glycosylation-9-2022-84d47

D-galactose for Congenital Disorder of Glycosylation In a pilot study with patients having PGM1-CDG, oral D-galactose supplementation was found to be safe, with no adverse effects reported.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1096719224004517

Treatment of congenital disorders of glycosylation The present paper aims to provide a detailed overview of these exciting developments and the rising concepts that are used to treat these ultra-rare diseases.

3. trial.medpath.com trial.medpath.com/clinical-trial/faaca73b82dad323/nct05402384-evaluation-efficacy-safety-d-galactose-slc35a2-cdg

AVTX-801 D-galactose Supplementation in SLC35A2-CDG This is a multicenter, randomized, double-blind, placebo-controlled, cross-over study to evaluate the efficacy and safety of AVTX-801 in subjects...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7980351/

D-galactose supplementation in individuals with PMM2-CDG Some CDG have been successfully treated with D-galactose. We performed an open-label pilot trial with D-galactose in 9 PMM2-CDG patients.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02955264?cond=%22Congenital%20Disorders%20of%20Glycosylation%22&viewType=Table&rank=5

Using D-Galactose as a Food Supplement in Congenital ... In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...

6. ir.avalotx.com ir.avalotx.com/news-events-presentations/press-releases/detail/72/cerecor-announces-positive-phase-i-safety-data-for-cerc-801-in-healthy-volunteers

Cerecor Announces Positive Phase I Safety Data for ... CERC-801 has been granted Orphan Drug Designation and awarded Rare Pediatric Disease Designation by the FDA, granting eligibility for receipt of ...