Venglustat vs Imiglucerase for Gaucher Disease

(LEAP2MONO Trial)

Recruiting at 48 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

43 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares a pill to injections in patients aged 12-18 and adults with Gaucher disease Type 3. The pill aims to help with brain symptoms, while the injections maintain overall health. The pill has the potential to improve Gaucher disease by rebalancing certain substances in the body.

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.

What data supports the effectiveness of the drug imiglucerase for Gaucher Disease?

Imiglucerase has been a standard treatment for Gaucher Disease, showing satisfactory clinical improvement in patients, even at low doses. It has been widely used and is effective in managing symptoms like anemia and organ enlargement. ^{1 2 3 4 5}

What is the safety profile of Venglustat and Imiglucerase for Gaucher Disease?

Imiglucerase is generally safe but can cause mild to moderate side effects, and some patients may develop antibodies. Venglustat, under the name miglustat, has many common side effects like diarrhea, weight loss, and tremors, and animal studies suggest it may affect reproduction. ^{1 6 7 8 9}

How does the drug Venglustat differ from other treatments for Gaucher Disease?

Venglustat is unique because it is an oral treatment, unlike the standard enzyme replacement therapies like imiglucerase, which are administered intravenously. This makes Venglustat potentially more convenient for patients who cannot receive intravenous treatments. ^{4 7 8 10 11}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Velaglucerase alfa enzyme replacement therapy compared with imiglucerase in patients with Gaucher disease. [2016]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment patterns from 647 patients with Gaucher disease: An analysis from the Gaucher Outcome Survey. [2018]

3. Italy pubmed.ncbi.nlm.nih.gov

Effects of switching from a reduced dose imiglucerase to velaglucerase in type 1 Gaucher disease: clinical and biochemical outcomes. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Velaglucerase alfa as a therapeutic option for Gaucher disease. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Low-dose low-frequency imiglucerase as a starting regimen of enzyme replacement therapy for patients with type I Gaucher disease. [2019]

6. United States 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. [2022]

7. France pubmed.ncbi.nlm.nih.gov

Miglustat: new drug. In type 1 Gaucher's disease : a slight benefit after imiglucerase therapy. [2007]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase. [2021]

9. United States 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. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Guidance on the use of miglustat for treating patients with type 1 Gaucher disease. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Oral maintenance clinical trial with miglustat for type I Gaucher disease: switch from or combination with intravenous enzyme replacement. [2021]