Phase 1/2 Clinical Trial of PR001 in Infants With Type 2 Gaucher Disease (PROVIDE)

NCT04411654 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: J3Z-MC-OJAB (PRV-GD2-101)
• Study Type: interventional
• Target: 7
• Locations: 2 countries
• Sites: 5

Brief Summary

J3Z-MC-OJAB is 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 Gaucher disease (GD2). For each patient, the study will be approximately 5 years in duration. During the first 12 months after dosing, patients will be evaluated for the effects of LY3884961 on safety, tolerability, immunogenicity, biomarkers, and efficacy. Patients will be followed up for an additional 4 years to monitor safety and changes on selected biomarkers and clinical outcomes.

Conditions

Gaucher Disease, Type 2

Keywords

Gaucher Disease; GD; Gaucher; Type 2 Gaucher; Neuronopathic Gaucher; nGD; AAV9; GBA; Gene Therapy; Glucocerebrosidase; GBA1 mutation; Infants

Outcome Measures

Primary Outcomes (3)

• Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events leading to discontinuation

  Year 5

• Immunogenicity of AAV9 and GCase in blood

  Up to Year 2

• Immunogenicity of AAV9 and GCase in CSF

  Up to Year 1

Secondary Outcomes (16)

• Time to death

  Baseline until event or study completion, up to Year 5

• Time to clinical event

  Baseline until event or study completion, up to Year 5

• Change in cognitive function

  Months 6,12 and up to Year 2

• Change in cognitive function

  Study Month 12 and up to Study Year 2

• Change in motor skills

  Months 6, 12 and up to Year 2

Study Arms (2)

Low Dose

EXPERIMENTAL

Genetic: LY3884961; Drug: Methylprednisolone; Drug: Sirolimus; Drug: Prednisone

High Dose

EXPERIMENTAL

Genetic: LY3884961; Drug: Methylprednisolone; Drug: Sirolimus; Drug: Prednisone

Interventions

LY3884961 GENETIC

Participants will receive a single dose of LY3884961 administered intracisternally.

High Dose; Low Dose

Methylprednisolone DRUG

Single IV pulse administered as concomitant medication.

High Dose; Low Dose

Sirolimus DRUG

Loading dose, followed by maintenance doses, followed by dose tapering; administered as concomitant medication.

High Dose; Low Dose

Prednisone DRUG

Administered orally as concomitant medication, followed by dose tapering.

High Dose; Low Dose

Eligibility Criteria

• Age: 0 Months - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Bi-allelic GBA1 mutations consistent with a diagnosis of GD2 confirmed by the central laboratory.
• Clinical diagnosis of GD2
• Parent/legal guardian is capable of providing signed informed consent; including compliance with the requirements and restrictions listed in the informed consent form (ICF) in this protocol.
• Patient has a parent/legal guardian able to participate in the study as a source of information on the patient's health status and cognitive and functional abilities (including providing input into the rating scales).

You may not qualify if:

• Significant CNS disease other than GD2 that may be a cause for the patient's symptoms or interfere with study objectives.
• Achieved independent gait.
• Severe peripheral symptoms of GD which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
• Concomitant disease, condition, or treatment which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
• Use of any substrate reduction therapy (SRT) for GD treatment.
• Use of prohibited medications, herbals, or over-the-counter agents as listed in the protocol.
• Any type of prior gene or cell therapy.
• Use of systemic immunosuppressant or corticosteroid therapy other than protocol-specified immunosuppression.
• Participation in another investigational drug or device study within the past 3 months.
• Brain MRI (magnetic resonance imaging) and MRA (magnetic resonance angiography) showing clinically significant abnormality deemed a contraindication to intracisternal injection.
• Clinically significant laboratory test result abnormalities assessed at screening.
• Contraindications or intolerance to radiographic visualization methods (e.g. MRI, MRA, CT), and intolerance to contrast agents used for MRI or CT scans.
• Contraindications to general anesthesia or sedation.

Sponsors & Collaborators

• Prevail Therapeutics: lead
• Eli Lilly and Company: collaborator

Study Sites (5)

UCSF Benioff Children's Hospital, 747 52nd St

Oakland, California, 94609, United States

Location

University of Minnesota Masonic Children's Hospital, 2450 Riverside Avenue

Minneapolis, Minnesota, 55454, United States

Location

Children's Hospital of Pittsburgh, 4401 Penn Avenue

Pittsburgh, Pennsylvania, 15224, United States

Location

Lysosomal & Rare Disorders Research and Treatment Center

Fairfax, Virginia, 22030, United States

Location

Manchester Centre for Genomic Medicine, 6th Floor, St Mary's Hospital, Oxford Road

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Gaucher Disease

Interventions

Methylprednisolone; Sirolimus; Prednisone

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Macrolides; Lactones; Organic Chemicals; Pregnadienediols

Study Officials

• Hamzeh Migdadi, M.D.

  Prevail Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Blinded assessor used in secondary outcome measures
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: June 2, 2020
• Study Start: June 29, 2021
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); GB (1)