LY3884961 for Gaucher Disease

Recruiting at 7 trial locations

Overseen By Prevail Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Prevail Therapeutics

Must be taking: ERT, SRT

Must not be taking: Chaperone therapy, Immunosuppressants

Disqualifiers: Neurological signs, Bone disease, Splenectomy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

15 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) for at least 2 years and on a stable dose for at least 3 months before joining. You cannot use GD-related chaperone therapy within 4 weeks before starting the trial.

How does the drug LY3884961 differ from other treatments for Gaucher Disease?

LY3884961 is a novel gene therapy approach for Gaucher Disease, which aims to address the root cause by delivering a functional copy of the GBA1 gene to cells, potentially offering a more long-term solution compared to existing enzyme replacement therapies that require regular infusions. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests a new drug called LY3884961 in adults with specific symptoms of Gaucher Disease. The study aims to find the safest and most effective dose by observing how patients' bodies react to different amounts of the drug. Researchers will monitor safety, side effects, and changes in disease symptoms over several years.

Research Team

Sarah Neuhaus, DO

Principal Investigator

Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly and Company

Eligibility Criteria

Adults aged 18-65 with Gaucher Disease (GD) and specific GBA1 mutations can join this trial. They must have been on enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) for at least 2 years, but not responding well enough. Participants need to use effective birth control and cannot donate blood for a year.

Inclusion Criteria

Patients must agree to abstain from blood donations for at least the first year of the study

My GBA1 mutations have been officially confirmed.

I have been on enzyme or substrate replacement therapy for 2 years and on a stable dose for the last 3 months.

Exclusion Criteria

My heart condition is stable and not considered serious by my doctor.

I have never received gene or cell therapy.

I am not on any immunosuppressants or steroids not allowed by the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Treatment

Participants receive a single intravenous dose of LY3884961 and are evaluated for safety, tolerability, immunogenicity, biomarkers, and efficacy

18 months

Follow-up

Participants are monitored for safety, immunogenicity, and selected biomarker and efficacy parameters

42 months

Treatment Details

Interventions

• LY3884961
• Methylprednisolone
• Prednisone
• Sirolimus

Trial Overview The study tests different doses of LY3884961 in adults with GD's peripheral symptoms. It's an open-label trial where everyone knows they're getting the drug, lasting about 5 years with close monitoring for safety, immune response, biomarkers, and effectiveness.

Participant Groups

Group I: LY3884961 Experimental Treatment 1 Intervention

LY3884961 is an advanced therapy investigational medicinal product administered as a single intravenous infusion.

LY3884961 is already approved in United States, European Union for the following indications:

Approved in United States as LY3884961 for:

• Type 1 Gaucher Disease (GD1)
• Type 2 Gaucher Disease (GD2)
• Parkinson's disease with GBA1 mutations (PD-GBA)

Approved in European Union as LY3884961 for:

• Type 1 Gaucher Disease (GD1)
• Type 2 Gaucher Disease (GD2)
• Parkinson's disease with GBA1 mutations (PD-GBA)

Who Is Running the Clinical Trial?

Prevail Therapeutics

Lead Sponsor

Trials

5

Recruited

190+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

The N370S allele is a key genetic marker for diagnosing type 1 Gaucher disease in the Ashkenazi Jewish population, while the L444P/L444P genotype is linked to more severe neuronopathic forms of the disease.

There is a significant underestimation of the prevalence of the N370S/N370S genotype in affected individuals, which has important implications for genetic counseling and understanding the disease's expression in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gaucher disease: gene frequencies and genotype/phenotype correlations. Grabowski, GA.[2022]

A novel mutation (V191G) in the glucocerebrosidase gene was identified in a patient with type 1 Gaucher disease, which may indicate a specific genetic profile affecting disease severity.

The presence of the N370S mutation alongside V191G suggests a potentially milder clinical course for this patient, as N370S is associated with less severe symptoms in type 1 Gaucher disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Mutations in brief no. 131. Online. Choy, FY., Humphries, ML., Ben-Yoseph, Y.[2013]

In a study of 46 patients with Gaucher's disease, 90% of type I patients had identifiable mutations, including a new recombinant mutation RecA456P, highlighting the genetic diversity of the disease.

The study found that the N370S mutation generally leads to milder adult-onset disease, but exceptions exist, indicating that genotype alone may not fully predict disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutation analysis in 46 British and Irish patients with Gaucher's disease. Hatton, CE., Cooper, A., Whitehouse, C., et al.[2019]

A study of 72 Brazilian patients with Gaucher disease identified 31 pathogenic variants in the GBA1 gene, with the N370S variant being the most common, found in 41% of cases.

The research suggests a stepwise genetic analysis approach for Brazilian patients, starting with exons 9 and 10 of the GBA1 gene, as this could streamline the diagnosis process while still being effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GBA1 variants in Brazilian Gaucher disease patients. Basgalupp, SP., Altmann, V., Vairo, FPE., et al.[2023]

Six new mutations linked to Gaucher disease were discovered in six unrelated patients, highlighting the genetic diversity of this condition.

Among the patients, four had type I Gaucher disease with milder symptoms, while two exhibited more severe forms with central nervous system involvement, indicating varying clinical presentations based on genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six new Gaucher disease mutations. Demina, A., Beutler, E.[2022]

References

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

Gaucher disease: gene frequencies and genotype/phenotype correlations. [2022]

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

A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Mutations in brief no. 131. Online. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Mutation analysis in 46 British and Irish patients with Gaucher's disease. [2019]

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

GBA1 variants in Brazilian Gaucher disease patients. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Six new Gaucher disease mutations. [2022]