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Active, Not Recruiting

NCT Number: NCT04411654

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Gaucher Disease, Type 2 Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Gaucher Disease Genetic Diseases, Inborn Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Sphingolipidoses

Age range

0 month–24 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

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

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LY3884961

Genetic

Participants will receive a single dose of LY3884961 administered intracisternally.

methylprednisolone

Drug

Single IV pulse administered as concomitant medication.

sirolimus

Drug

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

Prednisone

Drug

Administered orally as concomitant medication, followed by dose tapering.

Primary outcomes

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

    Time frame: Year 5

  2. Immunogenicity of AAV9 and GCase in blood

    Time frame: Up to Year 2

  3. Immunogenicity of AAV9 and GCase in CSF

    Time frame: Up to Year 1

Secondary outcomes

  1. Time to death

    Time frame: Baseline until event or study completion, up to Year 5

  2. Time to clinical event

    Time frame: Baseline until event or study completion, up to Year 5

    Clinical event defined as tracheostomy/invasive ventilation, and/or percutaneous endoscopic gastrostomy (PEG) tube placement, and/or nasogastric (NG) tube placement

  3. Change in cognitive function

    Time frame: Months 6,12 and up to Year 2

    Measured using Bayley Scales of Infant and Toddler Development (BSID-III)

  4. Change in cognitive function

    Time frame: Study Month 12 and up to Study Year 2

    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)

  5. Change in motor skills

    Time frame: Months 6, 12 and up to Year 2

    Change from baseline in motor function using Gross Motor Function Measure (GMFM-88).

  6. Change in motor skills

    Time frame: Months 6, 12 and up to Year 2

    Change from baseline in motor function using the BSID-III.

  7. Change in Clinical Global Impressions (Severity)

    Time frame: Months 6, 12 and up to Year 2

    Change from baseline in the clinical severity of illness (CGI-Severity {CGI-S}).

  8. Clinical Global Impressions (Improvement)

    Time frame: Months 6, 12 and up to Year 2

    Clinical improvement from baseline (CGI-Improvement [CGI-I]).

  9. Change in adaptive behavior and functioning

    Time frame: Months 6 and 12 and up to Year 2

    Change from baseline in adaptive functioning using the Vineland Adaptive Behavior Scale (VABS-2) (2nd edition)

  10. Change in most troubling symptoms

    Time frame: Months 6, 12 and up to Year 2

    Change from baseline in the Visual Analog Scale for the Most Troubling Symptoms (VAS-MTS)

  11. Change in behavioral symptoms

    Time frame: Months 6, 12 and up to Year 2

    Change from baseline in the Child Behavior Checklist (CBCL)

  12. Change in GCase (glucocerebrosidase) enzyme activity levels in blood

    Time frame: Up to Year 5

  13. Change in GCase enzyme activity levels in CSF (cerebrospinal fluid)

    Time frame: Up to Year 3

  14. Change in glycolipid levels in blood

    Time frame: Up to Year 5

  15. Change in glycolipid levels in CSF

    Time frame: Up to Year 3

  16. Individual Vector Shedding data

    Time frame: Up to Year 5

Sponsors and collaborators

Lead sponsor

Prevail Therapeutics

Industry

Collaborators

  • Eli Lilly and Company

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2028
Study completion
2028
First posted
Jun 2, 2020
Registry last updated
Apr 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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