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

Gaucher Disease, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04411654
• Other study ID #: J3Z-MC-OJAB (PRV-GD2-101)
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 29, 2021
• Est. completion date: May 2028

Study information

• Verified date: March 2024
• Source: Prevail Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: May 2028
• Est. primary completion date: May 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Months to 24 Months

Eligibility

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.

Related Conditions & MeSH terms

• Gaucher Disease
• Gaucher Disease, Type 2

Intervention

Genetic:
• LY3884961
Participants will receive a single dose of LY3884961 administered intracisternally.

Drug:
• 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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Prevail Therapeutics	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events leading to discontinuation		Year 5
Primary	Immunogenicity of AAV9 and GCase in blood		Up to Year 2
Primary	Immunogenicity of AAV9 and GCase in CSF		Up to Year 1
Secondary	Time to death		Baseline until event or study completion, up to Year 5
Secondary	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
Secondary	Change in cognitive function	Measured using Bayley Scales of Infant and Toddler Development (BSID-III)	Months 6,12 and up to Year 2
Secondary	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
Secondary	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
Secondary	Change in motor skills	Change from baseline in motor function using the BSID-III.	Months 6, 12 and up to Year 2
Secondary	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
Secondary	Clinical Global Impressions (Improvement)	Clinical improvement from baseline (CGI-Improvement [CGI-I]).	Months 6, 12 and up to Year 2
Secondary	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
Secondary	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
Secondary	Change in behavioral symptoms	Change from baseline in the Child Behavior Checklist (CBCL)	Months 6, 12 and up to Year 2
Secondary	Change in GCase (glucocerebrosidase) enzyme activity levels in blood		Up to Year 5
Secondary	Change in GCase enzyme activity levels in CSF (cerebrospinal fluid)		Up to Year 3
Secondary	Change in glycolipid levels in blood		Up to Year 5
Secondary	Change in glycolipid levels in CSF		Up to Year 3
Secondary	Individual Vector Shedding data		Up to Year 5