Clinical trial NCT04411654: Phase 1/2 Clinical Trial of PR001 in Infants With Type 2 Gaucher Disease (PROVIDE)
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gaucher Disease, Type 2
Keywords: Gaucher Disease
GD
Gaucher
Type 2 Gaucher
Neuronopathic Gaucher
nGD
AAV9
GBA
Gene Therapy
Glucocerebrosidase
GBA1 mutation
Infants
Lead sponsor: Prevail Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2020-06-02
Enrollment: 7
Sex: ALL
Minimum age (years): 0
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 outcomes:
measure: Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events leading to discontinuation
timeFrame: Year 5
measure: Immunogenicity of AAV9 and GCase in blood
timeFrame: Up to Year 2
measure: Immunogenicity of AAV9 and GCase in CSF
timeFrame: Up to Year 1
Secondary outcomes:
measure: Time to death
timeFrame: Baseline until event or study completion, up to Year 5
measure: Time to clinical event
timeFrame: Baseline until event or study completion, up to Year 5
measure: Change in cognitive function
timeFrame: Months 6,12 and up to Year 2
measure: Change in cognitive function
timeFrame: Study Month 12 and up to Study Year 2
measure: Change in motor skills
timeFrame: Months 6, 12 and up to Year 2
measure: Change in motor skills
timeFrame: Months 6, 12 and up to Year 2
measure: Change in Clinical Global Impressions (Severity)
timeFrame: Months 6, 12 and up to Year 2
measure: Clinical Global Impressions (Improvement)
timeFrame: Months 6, 12 and up to Year 2
measure: Change in adaptive behavior and functioning
timeFrame: Months 6 and 12 and up to Year 2
measure: Change in most troubling symptoms
timeFrame: Months 6, 12 and up to Year 2
measure: Change in behavioral symptoms
timeFrame: Months 6, 12 and up to Year 2
measure: Change in GCase (glucocerebrosidase) enzyme activity levels in blood
timeFrame: Up to Year 5
measure: Change in GCase enzyme activity levels in CSF (cerebrospinal fluid)
timeFrame: Up to Year 3
measure: Change in glycolipid levels in blood
timeFrame: Up to Year 5
measure: Change in glycolipid levels in CSF
timeFrame: Up to Year 3
measure: Individual Vector Shedding data
timeFrame: Up to Year 5
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital, 5700 Martin Luther King Jr Way
state: California
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Children's Hospital, 2450 Riverside Avenue
state: Minnesota
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh, 4401 Penn Avenue
state: Pennsylvania
city: Fairfax
country: United States
facility: Lysosomal Rare Disorders Research and Treatment Center
state: Virginia
city: Manchester
country: United Kingdom
facility: Manchester Centre for Genomic Medicine, 6th Floor, St Mary's Hospital, Oxford Road
Study officials:
affiliation: Prevail Therapeutics
name: Hamzeh Migdadi, M.D.
role: STUDY_DIRECTOR
References: