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

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ClinicalTrials.gov Identifier: NCT04411654
Recruitment Status : Recruiting
First Posted : June 2, 2020
Last Update Posted : July 8, 2021
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Prevail Therapeutics

Brief Summary:
PRV-GD2-101 is an open-label, Phase 1/2, multicenter study to evaluate the safety and efficacy of single-dose 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 PR001 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.

Condition or disease Intervention/treatment Phase
Gaucher Disease, Type 2 Biological: PR001 Drug: Methylprednisolone Drug: Sirolimus Drug: Prednisone Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Blinded assessor used in secondary outcome measures
Primary Purpose: Treatment
Official Title: An Open-label, Phase 1/2 Study to Evaluate the Safety and Efficacy of Single-dose PR001A in Infants With Type 2 Gaucher Disease
Actual Study Start Date : June 29, 2021
Estimated Primary Completion Date : September 2028
Estimated Study Completion Date : September 2028


Arm Intervention/treatment
Experimental: PR001 Biological: PR001
Participants will receive a single dose of PR001 administered intracisternally.

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.

Drug: Prednisone
Administered orally as concomitant medication, followed by dose tapering.




Primary Outcome Measures :
  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 3 ]

Secondary Outcome Measures :
  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 3 ]
    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 3 ]
    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 3 ]
    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 3 ]
    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 5 ]
    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 5 ]
    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 3 ]
    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 5 ]
    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 5 ]
    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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 24 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Bi-allelic GBA1 mutations consistent with a diagnosis of GD2 confirmed by the central laboratory.
  • Neurological signs and/or symptoms consistent with diagnosis of GD2
  • Parent/legal guardian has the ability to understand the purpose and risks of the study and provide written informed consent and authorization to use protected health information in accordance with national and local privacy regulations.
  • Patient has a reliable informant (i.e., parent/legal guardian) willing and 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:

  • Diagnosis of a significant CNS disease other than GD2 that may be a cause for the patient's GD symptoms or may confound 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 GD treatment-related substrate reduction therapy.
  • Use of strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (P-gp) medications, herbals, or over-the-counter agents.
  • Any type of prior gene or cell therapy.
  • Immunizations (live vaccines) in the prior 4 weeks.
  • Use of blood thinners. Antiplatelet therapies are acceptable if the patient is medically able to temporarily stop them from 7 days prior to dosing and through at least 48 hours after the intracisternal injection and lumbar puncture.
  • Use of systemic immunosuppressant or corticosteroid therapy other than protocol-specified (topical preparations for dermatological conditions are allowed).
  • Participation in another investigational drug or device study within the past 6 months.
  • Brain MRI (magnetic resonance imaging) and MRA (magnetic resonance angiography) showing clinically significant abnormality considered to prevent 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04411654


Contacts
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Contact: Prevail Therapeutics (917) 336-9310 patients@prevailtherapeutics.com

Locations
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United States, California
UCSF Benioff Children's Hospital, 5700 Martin Luther King Jr Way Not yet recruiting
Oakland, California, United States, 94609
Contact: Jill Nicholas    510-428-3885 ext 5241    jill.nicholas@ucsf.edu   
United States, Minnesota
University of Minnesota Masonic Children's Hospital, 2450 Riverside Avenue Recruiting
Minneapolis, Minnesota, United States, 55454
Contact: Carrie Gibson    612-672-7013    Cgibson1@fairview.org   
United States, Pennsylvania
Children's Hospital of Pittsburgh, 4401 Penn Avenue Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Jodi Martin       sausjl@upmc.edu   
Contact: Sarah Klotz       klotzse@upmc.edu   
United Kingdom
Manchester Centre for Genomic Medicine, 6th Floor, St Mary's Hospital, Oxford Road Not yet recruiting
Manchester, United Kingdom, M13 9WL
Contact: Laura Crowther    07815 987896    laura.crowther@mft.nhs.uk   
Sponsors and Collaborators
Prevail Therapeutics
Eli Lilly and Company
Investigators
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Study Director: Travis Lewis, MD, PhD Prevail Therapeutics
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Responsible Party: Prevail Therapeutics
ClinicalTrials.gov Identifier: NCT04411654    
Other Study ID Numbers: PRV-GD2-101
First Posted: June 2, 2020    Key Record Dates
Last Update Posted: July 8, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prevail Therapeutics:
Gaucher Disease
GD
Gaucher
Type 2 Gaucher
Neuronopathic Gaucher
nGD
AAV9
GBA
Gene Therapy
Glucocerebrosidase
GBA1 mutation
Infants
Additional relevant MeSH terms:
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Gaucher Disease
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
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Sirolimus
Prednisone
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal