Venglustat + Cerezyme for Gaucher Disease

(LEAP Trial)

Not currently recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genzyme, a Sanofi Company

Must be taking: Cerezyme

Must not be taking: Corticosteroids, Psoralens, Antipsychotics, others

Disqualifiers: Cancer, Renal insufficiency, Seizures, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Gaucher disease Type 3, a rare genetic disorder affecting various organs. The goal is to determine if a combination of two drugs, venglustat and Cerezyme (imiglucerase, an enzyme replacement therapy), is safe and effective, particularly in improving neurological symptoms and reducing organ sizes like the spleen and liver. The trial will also assess how well venglustat works on its own after combination therapy. Suitable candidates for this trial include individuals with Gaucher disease Type 3 who have been stable on enzyme replacement therapy for at least a year and do not have recent severe bone issues. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot take certain medications that affect liver enzymes or are known to cause cataracts, and you must avoid grapefruit products. It's best to discuss your current medications with the trial team.

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

Research has shown that venglustat, when combined with Cerezyme, is generally safe and well-tolerated for adults with Gaucher disease type 3. One study found that this combination had an acceptable safety profile, meaning it did not cause severe side effects for most people. The reported side effects were usually mild and manageable.

Another study examined venglustat used alone over three years and found it safe for long-term use in adults with Fabry disease, another rare condition. This finding suggests some confidence in its safety for other conditions, like Gaucher disease. In summary, while no treatment is without risk, current research indicates that venglustat is a safe option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Venglustat for Gaucher Disease because it offers a novel approach by targeting the root cause of the condition. Most treatments for Gaucher Disease, like enzyme replacement therapies such as Imiglucerase (Cerezyme), work by supplementing the enzyme that patients lack. However, Venglustat operates differently by inhibiting the production of glucosylceramide, the substance that builds up in the cells of people with Gaucher Disease. This new mechanism could potentially reduce the need for frequent enzyme infusions and offer a more convenient oral treatment option.

What evidence suggests that this trial's treatments could be effective for Gaucher Disease?

In this trial, participants will receive venglustat alongside their usual dose of Cerezyme. Studies have shown that combining venglustat with Cerezyme can significantly reduce certain harmful substances in the body. Over a year, 10 out of 11 patients experienced a noticeable drop in the levels of these substances in their blood and spinal fluid, indicating that the treatment can effectively address key issues in Gaucher Disease Type 3. Additionally, early patient reports suggest improvements in symptoms with venglustat therapy. The combination treatment also aims to improve organ size and blood counts, which are important health measures in Gaucher disease. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

Adults aged 18+ with Gaucher Disease Type 3 who have been on enzyme replacement therapy for at least 3 years and meet specific health goals can join. They must not be pregnant, agree to use contraception, and avoid grapefruit products. Exclusions include myoclonic seizures, severe kidney issues, hypersensitivity to Cerezyme, or other significant health problems.

Inclusion Criteria

I am willing to use birth control or practice abstinence during and after the study.

My Gaucher disease is under control, meeting all treatment goals.

My seizures are under control with medication that doesn't strongly affect CYP3A.

Exclusion Criteria

I experience sudden, brief muscle jerks.

I need regular blood transfusions to manage my condition.

I do not have any serious health issues other than Gaucher's disease that would stop me from joining.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

45 days

1 visit (in-person)

Biomarker Evaluation

Evaluate cerebrospinal fluid (CSF) biomarkers in adult Gaucher disease Type 3 (GD3) participants

45 days

Combination Treatment

Participants receive venglustat in combination with Cerezyme to evaluate short-term and long-term safety and tolerability

Up to 10 years

Regular visits as per protocol

Extended Treatment with Monotherapy

Evaluate safety and tolerability of venglustat monotherapy in participants who have remained stable

Up to 10 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Imiglucerase
• Venglustat

Trial Overview The trial tests the safety and effects of venglustat in combination with Cerezyme on brain biomarkers in adults with Gaucher Disease Type 3. It includes a screening phase followed by short-term and long-term treatment phases with both drugs, then an extension phase where only venglustat is given.

How Is the Trial Designed?

Group I: Open label (OL) venglustat Experimental Treatment 2 Interventions

Administered once a day orally for up to approximately 10 years. Participants will continue their usual dose of Cerezyme during Part 1, Part 2 and Part 3. There is no administration of Cerezyme in Part 4 unless administrated as rescue treatment.

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

Published Research Related to This Trial

In a Phase 2 trial involving 11 adults with Gaucher disease type 3, the investigational drug venglustat, when added to standard enzyme replacement therapy, demonstrated acceptable safety and tolerability over one year, with no serious adverse events reported.

Venglustat treatment resulted in significant reductions in glucosylceramide and glucosylsphingosine levels in both plasma and cerebrospinal fluid, suggesting potential efficacy in addressing the biochemical aspects of the disease, although overall neurological function showed signs of deterioration over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venglustat combined with imiglucerase for neurological disease in adults with Gaucher disease type 3: the LEAP trial. Schiffmann, R., Cox, TM., Dedieu, JF., et al.[2023]

In a study involving 211 patients with type 1 Gaucher disease, velaglucerase alfa was found to have a safety profile similar to that of imiglucerase, with only 17.1% of previously treated patients experiencing related adverse events.

The treatment was well-tolerated, with infusion-related adverse events occurring in 13.3% of patients, primarily during the first three infusions, and no significant immune responses observed in treatment-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter open-label treatment protocol (HGT-GCB-058) of velaglucerase alfa enzyme replacement therapy in patients with Gaucher disease type 1: safety and tolerability. Pastores, GM., Rosenbloom, B., Weinreb, N., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9924909/

Venglustat combined with imiglucerase for neurological ... Over 1 year of venglustat treatment, concentrations of glucosylceramide and glucosylsphingosine in plasma and CSF decreased markedly in 10 out of 11 patients; ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05222906

Study to Evaluate the Efficacy and Safety of Venglustat in ... Study to Evaluate the Efficacy and Safety of Venglustat in Adult and Pediatric Patients With Gaucher Disease Type 3 (LEAP2MONO). ClinicalTrials.gov ID ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38802634/

Qualitative Study of the Patient Experience with Venglustat ... Outcomes from this study provide insights into GD3 symptoms and the early signaling of changes reported during venglustat therapy.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1096719222004322

Assessment over 3 years in adult males with classic Fabry ... Venglustat treatment reduced markers in the synthetic and degradative pathway of major glycosphingolipids; proximal markers reduced rapidly and more distal ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02843035

NCT02843035 | Venglustat in Combination With Cerezyme ... Evaluate the efficacy of venglustat in combination with Cerezyme in systemic disease in adult GD3 participants by assessing spleen volume, liver volume, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7818513/

Pharmacokinetics, Pharmacodynamics, Safety, and ... Venglustat in adult Gaucher disease type 3: Preliminary safety, pharmacology, and exploratory efficacy from a phase 2 trial in combination with imiglucerase ...

7. link.springer.com link.springer.com/article/10.1007/s12325-024-02881-2

Qualitative Study of the Patient Experience with Venglustat ... Participants in the qualitative study perceived a treatment benefit in cognitive, neurologic, and functional symptoms with venglustat in ...