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

An Open-label, Phase 1/2 Study to Evaluate the Safety and Efficacy of Single-dose LY3884961 in Infants With Type 2 Gaucher Disease

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Gaucher Disease, Type 2
• Intervention / Treatment: Drug: Prednisone; Drug: Methylprednisolone; Drug: Sirolimus; Genetic: LY3884961

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Prevail Therapeutics; Phone Number: (917) 336-9310; Email: prevail.patients@lilly.com

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Manchester Centre for Genomic Medicine, 6th Floor, St Mary's Hospital, Oxford Road
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital, 5700 Martin Luther King Jr Way
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Masonic Children's Hospital, 2450 Riverside Avenue
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh, 4401 Penn Avenue
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal Rare Disorders Research and Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Dose	Drug: Prednisone; Administered orally as concomitant medication, followed by dose tapering.; Drug: Methylprednisolone; Single IV pulse administered as concomitant medication.; Drug: Sirolimus; Loading dose, followed by maintenance doses, followed by dose tapering; administered as concomitant medication.; Genetic: LY3884961; Participants will receive a single dose of LY3884961 administered intracisternally.
Experimental: Low Dose	Drug: Prednisone; Administered orally as concomitant medication, followed by dose tapering.; Drug: Methylprednisolone; Single IV pulse administered as concomitant medication.; Drug: Sirolimus; Loading dose, followed by maintenance doses, followed by dose tapering; administered as concomitant medication.; Genetic: LY3884961; Participants will receive a single dose of LY3884961 administered intracisternally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to death		Baseline until event or study completion, up to Year 5
Time to clinical event	Clinical event defined as tracheostomy/invasive ventilation, and/or percutaneous endoscopic gastrostomy (PEG) tube placement, and/or nasogastric (NG) tube placement	Baseline until event or study completion, up to Year 5
Change in GCase (glucocerebrosidase) enzyme activity levels in blood		Up to Year 5
Change in GCase enzyme activity levels in CSF (cerebrospinal fluid)		Up to Year 3
Change in glycolipid levels in blood		Up to Year 5
Change in glycolipid levels in CSF		Up to Year 3
Individual Vector Shedding data		Up to Year 5
Change in cognitive function	Measured using Bayley Scales of Infant and Toddler Development (BSID-III)	Months 6,12 and up to Year 2
Change in cognitive function	Measured using Wechsler Preschool and Primary Scale of Intelligence (WPPSI-IV) as appropriate. (Not all patients begin the study at birth. Only patients who are age 36 months at the designated study visits will be assessed using this measure)	Study Month 12 and up to Study Year 2
Change in motor skills	Change from baseline in motor function using Gross Motor Function Measure (GMFM-88).	Months 6, 12 and up to Year 2
Change in motor skills	Change from baseline in motor function using the BSID-III.	Months 6, 12 and up to Year 2
Change in Clinical Global Impressions (Severity)	Change from baseline in the clinical severity of illness (CGI-Severity {CGI-S}).	Months 6, 12 and up to Year 2
Clinical Global Impressions (Improvement)	Clinical improvement from baseline (CGI-Improvement [CGI-I]).	Months 6, 12 and up to Year 2
Change in adaptive behavior and functioning	Change from baseline in adaptive functioning using the Vineland Adaptive Behavior Scale (VABS-2) (2nd edition)	Months 6 and 12 and up to Year 2
Change in most troubling symptoms	Change from baseline in the Visual Analog Scale for the Most Troubling Symptoms (VAS-MTS)	Months 6, 12 and up to Year 2
Change in behavioral symptoms	Change from baseline in the Child Behavior Checklist (CBCL)	Months 6, 12 and up to Year 2

Collaborators and Investigators

• Sponsor: Prevail Therapeutics
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: Sarah Neuhaus, D.O., Prevail Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2021
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 29, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Gene Therapy; Infants; Gaucher Disease; Glucocerebrosidase; Gaucher; AAV9; GBA1 mutation; GBA; GD; Type 2 Gaucher; Neuronopathic Gaucher; nGD
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease; Physiological Effects of Drugs; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone; Sirolimus
• Other Study ID Numbers: J3Z-MC-OJAB (PRV-GD2-101)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No