Venglustat for Tay-Sachs Disease

(AMETHIST Trial)

No longer recruiting at 42 trial locations

Overseen By Trial Transparency email recommended (Toll free number for US & Canada)

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Genzyme, a Sanofi Company

Must not be taking: Anticoagulants, Cataractogenic, CYP3A4 inducers

Disqualifiers: Hepatitis B/C, HIV, Cataracts, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness of a drug called venglustat for individuals with certain rare diseases, such as Tay-Sachs disease and similar conditions. Participants will take a daily pill for about two years to assess its impact on symptom management and the body's response to the drug. The trial seeks adults with late-onset Tay-Sachs or similar conditions, particularly those experiencing frequent issues affecting daily life. This is an opportunity to contribute to research that could lead to new treatments for these challenging diseases. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to be part of potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial requires you to stop taking certain medications, like strong or moderate inducers or inhibitors of CYP3A4, at least 14 days before joining. You also need to avoid grapefruit products 72 hours before starting the trial. If you're on anticoagulants or medications that could worsen cataracts, you may not be eligible.

Is there any evidence suggesting that venglustat is likely to be safe for humans?

Research has shown that venglustat is generally well-tolerated. In studies with healthy volunteers, a single oral dose of venglustat proved safe, causing no major side effects.

For individuals with GM2 gangliosidoses, including Tay-Sachs disease, ongoing studies aim to understand its long-term safety. These studies examine how the body processes venglustat over time and any side effects from daily use. So far, most participants find the treatment manageable.

Venglustat is currently in a late-stage trial, indicating that earlier studies deemed it safe enough for larger group testing. However, ongoing studies will provide more detailed information about its long-term safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Venglustat for Tay-Sachs disease because it offers a novel approach by targeting glucosylceramide buildup, the underlying cause of the condition. Unlike current treatments, which primarily focus on managing symptoms, Venglustat acts by inhibiting the enzyme glucosylceramide synthase, potentially slowing the progression of the disease. This mechanism of action is unique and could significantly improve outcomes for patients by addressing the root of the problem rather than just alleviating symptoms.

What evidence suggests that venglustat might be an effective treatment for Tay-Sachs disease?

Research suggests that venglustat, which participants in this trial may receive, might help treat Tay-Sachs disease by targeting a specific enzyme related to the condition. Studies have shown that venglustat can enter the brain and block an enzyme called glucosylceramide synthase, which contributes to the disease. This action could slow the disease by reducing harmful substances that accumulate in the brain. Although no cure exists for Tay-Sachs, early findings indicate that venglustat could be a promising treatment by addressing the disorder's underlying cause. ^{1 2 3 5 6}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

Adults and juveniles with late-onset GM2 gangliosidosis (Tay-Sachs or Sandhoff disease) can join this trial. Adults must be over 18, while juveniles should be at least 2 years old but under 18 and weigh more than 10 kg. Participants need to control any seizures with certain medications, not have other health issues that could interfere, and agree to use contraception if applicable.

Inclusion Criteria

I can take pills, travel to the study site, and follow the study's requirements.

My seizures are under control with medication that doesn't strongly affect CYP3A4.

I have been diagnosed with a specific genetic disorder affecting my nervous system.

Exclusion Criteria

I do not have any health conditions that would make the trial unsafe for me.

Current participation in another study

I am currently taking medication that could affect my vision or worsen cataracts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8-9 weeks

Treatment

Participants receive daily oral dosing of venglustat or placebo for 104 weeks

104 weeks

Open-label extension

Participants receive venglustat dose once daily during the open-label extension period

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Venglustat

Trial Overview The study is testing the effectiveness of a drug called Venglustat taken daily for two years compared to a placebo. It will look at how well it works (efficacy), its effects on the body (pharmacodynamics), how it's processed by the body (pharmacokinetics), and its safety in patients with Tay-Sachs or Sandhoff disease.

How Is the Trial Designed?

Group I: GZ402671 Experimental Treatment 1 Intervention

Primary population: participant will receive venglustat dose once daily during the primary analysis period (104 weeks) and the open-label extension period (104 weeks). Secondary population: participant will receive venglustat at various doses once daily during the primary analysis period open-label (104 weeks) and the open-label extension period (104 weeks).

Group II: Placebo Placebo Group 1 Intervention

Primary population: participants will receive placebo once daily during the primary analysis period (104 weeks) and will receive venglustat dose once daily during the open-label extension period (104 weeks).

Who Is Running the Clinical Trial?

Genzyme, a Sanofi Company

Lead Sponsor

Trials

528

Recruited

186,000+

David Meeker

Genzyme, a Sanofi Company

Chief Executive Officer since 2011

MD from the University of Vermont Medical School, Advanced Management Program at Harvard Business School

Jean-Paul Kress

Genzyme, a Sanofi Company

Chief Medical Officer since 2015

MD from Faculte Necker-Enfants Malades, Paris

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S109836002500262X

Venglustat in GM2 Gangliosidoses and Related Disorders Abstract. Purpose. To evaluate efficacy and safety of venglustat for GM2 gangliosidoses (Tay-Sachs and Sandhoff diseases) and cognate diseases.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04221451

Study Details | NCT04221451 | A Multinational, ... A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late ...

3. gimjournal.org gimjournal.org/article/S1098-3600(25)00262-X/pdf

Venglustat in GM2 Gangliosidoses and Related Disorders Purpose: To evaluate efficacy and safety of venglustat for GM2 gangliosidoses (Tay-Sachs and. Sandhoff diseases) and cognate diseases.

4. horizonscandb.pcori.org horizonscandb.pcori.org/report/topics/592

Venglustat to treat GM2 gangliosidosis No cure or effective treatments exist for GM2 gangliosidosis. Venglustat purportedly crosses the blood-brain barrier and inhibits glucosylceramide synthase, an ...

5. withpower.com withpower.com/trial/phase-3-sandhoff-disease-5-2020-b2961

Venglustat for Tay-Sachs Disease (AMETHIST Trial) It will look at how well it works (efficacy), its effects on the body (pharmacodynamics), how it's processed by the body (pharmacokinetics), and its safety in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10299927/

Pharmacokinetics, Safety, and Tolerability of Single-Dose ... Venglustat showed a favorable pharmacokinetic, safety, and tolerability profile in healthy Chinese volunteers following a single oral 15 mg dose.