What side effects are associated with this type of intervention?

Common treatments for Fabry Disease, such as enzyme replacement therapy (ERT) and chaperone therapy, have known side effects. ERT can cause infusion-related reactions like fever, chills, and headaches, as well as allergic reactions. Chaperone therapy may lead to gastrointestinal symptoms, headaches, and fatigue. Treatments like Venglustat, which inhibit glucosylceramide synthase, may cause gastrointestinal disturbances, liver enzyme elevations, and potential impacts on kidney function.

What prior FDA approvals exist?

The FDA has approved several treatments for Fabry Disease, primarily focusing on enzyme replacement therapies (ERTs) such as agalsidase beta (Fabrazyme) and agalsidase alfa (Replagal). These treatments work by supplementing the deficient enzyme alpha-galactosidase A, which helps reduce the accumulation of globotriaosylceramide (GL-3) in cells. While Venglustat, which inhibits glucosylceramide synthase to reduce glycosphingolipid accumulation, represents a different therapeutic approach, it is part of ongoing efforts to address the underlying metabolic dysfunction in Fabry Disease.

What other types of research exist?

Promising alternatives to Venglustat for Fabry Disease include: 1) Enzyme Replacement Therapy (ERT) with agalsidase beta or agalsidase alfa, which replaces the deficient enzyme alpha-galactosidase A. 2) Chaperone therapy with migalastat, which stabilizes the endogenous enzyme. 3) Gene therapy approaches, such as ST-920 (an investigational gene therapy delivering a functional copy of the GLA gene). 4) Other substrate reduction therapies (SRT) under investigation, like lucerastat, which also targets glycosphingolipid accumulation.

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Substrate Reduction Therapy

Venglustat for Fabry Disease (PERIDOT Trial)

Phase 3

Recruiting

Research Sponsored by Sanofi

Eligibility Criteria Checklist

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

Must have

Male and female adult patients 16 years of age or older, with a previously confirmed diagnosis of Fabry disease and a history of clinical symptoms of Fabry disease

Average score of ≥3 on the participant-defined most-bothersome symptom (among neuropathic pain in upper extremities, neuropathic pain in lower extremities, or abdominal pain), as measured by the Fabry Disease Patient-Reported Outcome (FD-PRO) at screening

Must not have

Moderate to severe hepatic impairment

History of or active hepatobiliary disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 6 months and 12 months

Awards & highlights

Pivotal Trial

Summary

This trial is testing a medication called venglustat to see if it can help reduce pain in people with Fabry disease. The medication works by targeting the root causes of nerve and abdominal pain.

Who is the study for?

Adults with Fabry disease experiencing neuropathic or abdominal pain can join this trial if they haven't had treatments for Fabry in the last 6 months. They must have a confirmed diagnosis, be at least 18 years old, and agree to use double contraception methods. Exclusions include recent changes in pain meds, certain cardiovascular issues, uncontrolled hypertension, severe liver problems, active infections like COVID-19 within specific timeframes.

What is being tested?

The study is testing Venglustat tablets against placebo over a year to see if they reduce neuropathic and abdominal pain in adults with Fabry disease. Participants will either get the real drug or a dummy pill without knowing which one. After this 'blind' phase, there's an extra year where everyone gets Venglustat.

What are the potential side effects?

While not specified here, potential side effects of Venglustat may include typical drug reactions such as digestive discomforts (nausea/vomiting), headaches, dizziness or fatigue. Since it's under study its full range of side effects are still being evaluated.

Eligibility Criteria

Inclusion Criteria

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

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I am 16 or older with a confirmed diagnosis and symptoms of Fabry disease.

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My worst symptom from Fabry disease scores 3 or more on the FD-PRO.

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I weigh 30 kg or more.

Exclusion Criteria

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

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My liver does not work well.

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I have a history of liver or bile duct disease.

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I have hepatitis C, HIV, or hepatitis B.

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I haven't taken strong or moderate drugs that affect liver enzymes in the last 14 days or more.

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I am currently being treated for seizures.

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I have nerve pain in my arms, legs, or stomach not due to Fabry disease.

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My kidney function is reduced.

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My Fabry disease symptoms are too severe for a placebo.

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I have a history of heart or major cardiovascular issues, or kidney transplantation.

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I tested positive for COVID-19 recently or was hospitalized for it in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 6 months and 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 6 months and 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 6 months and 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Frequency of rescue pain medication use

Proportion of responders in neuropathic or abdominal pain, as assessed by FD-PRO

Awards & Highlights

Pivotal Trial

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

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: VenglustatExperimental Treatment1 Intervention

Participant will receive venglustat dose once daily up to 12 months

Group II: PlaceboPlacebo Group1 Intervention

Participants will receive placebo once daily up to 12 months

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venglustat (GZ402671)

2023

Completed Phase 1

~30

0 / 13Eligibility 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 Fabry Disease include enzyme replacement therapy (ERT) and small molecule inhibitors like Venglustat. Venglustat works by inhibiting glucosylceramide synthase, thereby reducing the accumulation of glycosphingolipids in cells, which is a key factor in the pathology of Fabry Disease. This reduction in lipid accumulation helps alleviate symptoms such as neuropathic and abdominal pain. ERT, on the other hand, involves the intravenous administration of recombinant enzymes to replace the deficient alpha-galactosidase A enzyme, thereby reducing the buildup of globotriaosylceramide (GL-3) in various tissues. Both treatments aim to manage symptoms and improve the quality of life for Fabry Disease patients by addressing the underlying biochemical abnormalities.