Venglustat vs Imiglucerase for Gaucher Disease

(LEAP2MONO Trial)

Not currently recruiting at 52 trial locations

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

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Genzyme, a Sanofi Company

Must be taking: Enzyme replacement therapy

Must not be taking: CYP3A inducers/inhibitors

Disqualifiers: Blood transfusion-dependent, Cancer, Epilepsy, others

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

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: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for Gaucher Disease Type 3, a condition that impairs the body's ability to break down certain fats, leading to various health issues, including neurological problems. One group will take venglustat in pill form daily, while the other will receive Cerezyme (imiglucerase) infusions every two weeks. Researchers aim to determine which treatment better improves or stabilizes neurological symptoms and controls other symptoms. Participants should have been on enzyme replacement therapy for at least three years and experience issues like difficulty with eye movements.

As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take strong or moderate inducers or inhibitors of CYP3A within 14 days before starting the trial. You also need to avoid grapefruit products during the treatment period.

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

Research has shown that venglustat is safe and well-tolerated in adults with Gaucher disease type 3. In earlier studies, when combined with the enzyme replacement therapy Cerezyme (imiglucerase), venglustat was generally well-received by patients. These studies reported no significant side effects from the treatment.

Venglustat has also undergone study for up to 3 years in individuals with Fabry disease, another condition. This long-term research also found the treatment to be safe and well-tolerated. These results support the continued testing of venglustat for Gaucher disease type 3. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Gaucher disease?

Unlike the standard of care for Gaucher disease, which typically involves enzyme replacement therapy like Cerezyme, Venglustat offers a unique approach by targeting a different part of the disease process. Venglustat is an oral medication that works by inhibiting glucosylceramide synthase, aiming to reduce the accumulation of fatty substances in cells. This mechanism of action is distinct from enzyme replacement therapies and could potentially offer a more convenient treatment option with the flexibility of oral administration. Researchers are excited about Venglustat because it could simplify treatment regimens and improve quality of life for patients with Gaucher disease.

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

This trial will compare Venglustat with Imiglucerase (Cerezyme) for treating Gaucher disease. Research has shown that Venglustat may help treat Gaucher disease Type 3. In an earlier study, Venglustat significantly lowered harmful substances in the blood and spinal fluid of most patients. This suggests it might help improve or stabilize problems with movement and thinking. Some patients noticed early changes in their symptoms while taking Venglustat, indicating it could be effective. Overall, the evidence supports Venglustat as a potentially effective treatment for Gaucher disease Type 3. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

This trial is for adults and children aged ≥12 with Gaucher Disease Type 3 (GD3) who have been on Enzyme Replacement Therapy for at least 3 years. They must not be pregnant, breastfeeding, or planning to donate sperm; should weigh over 30 kg; and have controlled seizures if present. Exclusions include those needing ventilatory support, with allergies to study drugs, recent use of certain CYP3A affecting substances including grapefruit products, history of cancer (except basal cell carcinoma), planned hospitalizations, significant other diseases or conditions that could interfere with the study.

Inclusion Criteria

Signed written informed assent/consent

My balance and coordination are affected.

I weigh at least 30 kg.

Exclusion Criteria

Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures

My liver function tests are not more than twice the normal limit, unless I have Gilbert Syndrome.

My kidney function is low, with a filtration rate under 30 mL/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment

Participants receive daily oral venglustat or intravenous Cerezyme infusions every two weeks for 52 weeks

52 weeks

Open-label extension

Participants may continue treatment with venglustat for a minimum of 52 weeks

Minimum of 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment via a phone call

30-37 days

What Are the Treatments Tested in This Trial?

Interventions

• imiglucerase
• Venglustat

Trial Overview The trial compares the effectiveness and safety of an oral drug called Venglustat against intravenous infusions of Imiglucerase (Cerezyme). It's designed as a Phase 3 study where participants are randomly assigned to one of two groups: one taking Venglustat daily by mouth and the other receiving Cerezyme injections every two weeks. The goal is to see which treatment better improves or stabilizes neurological symptoms while maintaining overall health in GD3 patients.

How Is the Trial Designed?

Group I: Venglustat Experimental Treatment 1 Intervention

Venglustat

Group II: Cerezyme Active Control 1 Intervention

Cerezyme

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

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

In a multicenter study involving 15 pediatric patients with Gaucher disease, taliglucerase alfa significantly improved key health markers, such as reducing spleen and liver volumes and increasing hemoglobin and platelet counts over 36 months for treatment-naïve patients.

For patients who switched from imiglucerase, taliglucerase alfa maintained stable disease parameters over 33 months, demonstrating its effectiveness and safety, with most side effects being mild to moderate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of taliglucerase alfa in pediatric Gaucher disease patients who were treatment-naïve or previously treated with imiglucerase. Zimran, A., Gonzalez-Rodriguez, DE., Abrahamov, A., et al.[2018]

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.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-venglustat-for-adults-and-children-with-gaucher-disease-type-3/

Study on the Effectiveness and Safety of Venglustat ... The purpose of the study is to see how well venglustat works in improving symptoms of Gaucher disease Type 3, such as problems with movement and thinking ...

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. academic.oup.com academic.oup.com/brain/article/146/2/461/6763138

Venglustat combined with imiglucerase for neurological ... In adults with Gaucher disease type 3 receiving imiglucerase, addition of once-daily venglustat showed acceptable safety and tolerability and preliminary ...

8. gaucherdisease.org gaucherdisease.org/blog/gaucher-disease-treatment-on-the-horizon/

Gaucher Disease Treatment: What's on the Horizon? Phase 2 trials showed venglustat—when taken in combination with the ERT Cerezyme (imiglucerase)—is safe and tolerable. Phase 3 trials are in progress. “In my ...