LY3884961: Participants will receive a single dose of LY3884961 administered intracisternally.
Methylprednisolone: Single IV pulse administered as concomitant medication.
Sirolimus: Loading dose, followed by maintenance doses, followed by dose tapering; administered as concomitant medication.
Prednisone: Administered orally as concomitant medication, followed by dose tapering.
Study 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.
Eligibility
Sex
ALL
Min age
0 Months
Max age
24 Months
Healthy volunteers
No
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.
Primary outcome measure(s)
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
Trial sites (6)
Facility
City
Region
Status
UCSF Benioff Children's Hospital, 747 52nd St
Oakland
California
University of Minnesota Masonic Children's Hospital, 2450 Riverside Avenue
Minneapolis
Minnesota
NYU Medical Center, 305 Second Ave, Suite 16
New York
New York
Children's Hospital of Pittsburgh, 4401 Penn Avenue
Pittsburgh
Pennsylvania
Lysosomal & Rare Disorders Research and Treatment Center
Fairfax
Virginia
Manchester Centre for Genomic Medicine, 6th Floor, St Mary's Hospital, Oxford Road
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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