LY3884961 for Gaucher Disease

Recruiting at 10 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, LY3884961, to determine its safety and effectiveness for adults with Gaucher Disease, which affects organs like the liver and spleen. Researchers will administer the treatment to small groups to identify the best dose and monitor for side effects or symptom improvements. The trial is open to those who have managed Gaucher Disease with enzyme replacement or substrate reduction therapy for at least two years. Participants will receive a single intravenous infusion and be monitored over several years to track health outcomes. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

Is there any evidence suggesting that LY3884961 is likely to be safe for humans?

Research shows that LY3884961, also known as PR001, is under study to determine its safety and tolerability for treating Gaucher Disease. Previous studies have primarily examined patient responses and potential side effects, including immune reactions and key health indicators over time.

Detailed safety information for LY3884961 is still being collected, as the treatment is in early testing stages. Researchers are assessing its safety and patient tolerance. Treatments at this stage are closely monitored for adverse reactions.

Since LY3884961 is also under investigation for Type 1 Gaucher Disease, some basic safety checks have likely been completed. However, ongoing trials will provide a clearer understanding of its safety in humans. Participants in these studies contribute valuable information about potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Gaucher disease, which typically involve enzyme replacement therapies like imiglucerase or substrate reduction therapies, LY3884961 is unique because it is an advanced therapy investigational medicinal product delivered through a single intravenous infusion. Researchers are excited about LY3884961 because it potentially offers a new mechanism of action, targeting the disease differently than existing therapies. This innovative approach could lead to longer-lasting effects and reduced treatment frequency, which are significant advantages over current options.

What evidence suggests that LY3884961 might be an effective treatment for Gaucher Disease?

Research shows that LY3884961, also known as PR001, is a new gene therapy under development for Gaucher disease. Early studies suggest that this treatment might reduce symptoms and slow or halt the progression of Gaucher disease type 1. In this trial, participants will receive LY3884961 as a one-time infusion into a vein. The trial tests the treatment's safety and effectiveness against the disease. While researchers are still collecting complete results, the aim is to improve patients' quality of life by targeting the disease's root cause. ^{1 2 4 6 7}

Who Is on the Research Team?

Sarah Neuhaus, DO

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05487599

NCT05487599 | A Clinical Trial of PR001 (LY3884961) in ... During the first 18 months after dosing, subjects will be evaluated for the effects of LY3884961 on safety, tolerability, immunogenicity, biomarkers, and ...

2. gaucherdiseasenews.com gaucherdiseasenews.com/pr001/

PR001 for Gaucher disease type 1 PR001 is an experimental gene therapy being developed to ease symptoms and slow or halt disease progression in people with Gaucher disease type 1.

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT04411654

PR001 in Infants With Type 2 Gaucher Disease (PROVIDE) An open-label, Phase 1/2, multicenter study to evaluate the safety and efficacy of single-dose LY3884961 (formerly PR001) in infants diagnosed with Type 2 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04411654

Study Details | NCT04411654 | Phase 1/2 Clinical Trial of ... During the first 12 months after dosing, patients will be evaluated for the effects of LY3884961 on safety, tolerability, immunogenicity, biomarkers, and ...

5. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/J3Z-MC-OJAE

LY3884961 in Patients With Peripheral Manifestations of ... The purpose of this study is to evaluate the safety and tolerability of an experimental drug called LY3884961 in people with Gaucher disease (GD).

6. trials.lilly.com trials.lilly.com/en-US/trial/425855

A Clinical Trial of PR001 (LY3884961) in Patients With ... The main purpose of this study is to evaluate the safety and tolerability of LY3884961 (PR001) in adult participants with Type 1 Gaucher Disease.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10970163/

Advancements in Viral Gene Therapy for Gaucher Disease This review aimed to discuss the progress, advances, and challenges in developing viral gene therapy as a treatment for Gaucher disease.