<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04411654</url>
  </required_header>
  <id_info>
    <org_study_id>J3Z-MC-OJAB (PRV-GD2-101)</org_study_id>
    <nct_id>NCT04411654</nct_id>
  </id_info>
  <brief_title>Phase 1/2 Clinical Trial of PR001 in Infants With Type 2 Gaucher Disease (PROVIDE)</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Prevail Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Prevail Therapeutics</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      J3Z-MC-OJAB is an open-label, Phase 1/2, multicenter study to evaluate the safety and&#xD;
      efficacy of single-dose LY3884961 (formerly PR001) in infants diagnosed with Type 2 Gaucher&#xD;
      disease (GD2). For each patient, the study will be approximately 5 years in duration. During&#xD;
      the first 12 months after dosing, patients will be evaluated for the effects of LY3884961 on&#xD;
      safety, tolerability, immunogenicity, biomarkers, and efficacy. Patients will be followed up&#xD;
      for an additional 4 years to monitor safety and changes on selected biomarkers and clinical&#xD;
      outcomes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 29, 2021</start_date>
  <completion_date type="Anticipated">September 2028</completion_date>
  <primary_completion_date type="Anticipated">September 2028</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Blinded assessor used in secondary outcome measures</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events leading to discontinuation</measure>
    <time_frame>Year 5</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunogenicity of AAV9 and GCase in blood</measure>
    <time_frame>Up to Year 2</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Immunogenicity of AAV9 and GCase in CSF</measure>
    <time_frame>Up to Year 3</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to death</measure>
    <time_frame>Baseline until event or study completion, up to Year 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to clinical event</measure>
    <time_frame>Baseline until event or study completion, up to Year 5</time_frame>
    <description>Clinical event defined as tracheostomy/invasive ventilation, and/or percutaneous endoscopic gastrostomy (PEG) tube placement, and/or nasogastric (NG) tube placement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cognitive function</measure>
    <time_frame>Months 6, 12 and up to Year 3</time_frame>
    <description>Measured using Bayley Scales of Infant and Toddler Development (BSID-III)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in cognitive function</measure>
    <time_frame>Study Month 12 and up to Study Year 3</time_frame>
    <description>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)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in motor skills</measure>
    <time_frame>Months 6, 12 and up to Year 3</time_frame>
    <description>Change from baseline in motor function using Gross Motor Function Measure (GMFM-88).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in motor skills</measure>
    <time_frame>Months 6, 12 and up to Year 3</time_frame>
    <description>Change from baseline in motor function using the BSID-III.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Global Impressions (Severity)</measure>
    <time_frame>Months 6, 12 and up to Year 5</time_frame>
    <description>Change from baseline in the clinical severity of illness (CGI-Severity {CGI-S}).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impressions (Improvement)</measure>
    <time_frame>Months 6, 12 and up to Year 5</time_frame>
    <description>Clinical improvement from baseline (CGI-Improvement [CGI-I]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in adaptive behavior and functioning</measure>
    <time_frame>Months 6 and 12 and up to Year 3</time_frame>
    <description>Change from baseline in adaptive functioning using the Vineland Adaptive Behavior Scale (VABS-2) (2nd edition)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in most troubling symptoms</measure>
    <time_frame>Months 6, 12 and up to Year 5</time_frame>
    <description>Change from baseline in the Visual Analog Scale for the Most Troubling Symptoms (VAS-MTS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in behavioral symptoms</measure>
    <time_frame>Months 6, 12 and up to Year 5</time_frame>
    <description>Change from baseline in the Child Behavior Checklist (CBCL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in GCase (glucocerebrosidase) enzyme activity levels in blood</measure>
    <time_frame>Up to Year 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in GCase enzyme activity levels in CSF (cerebrospinal fluid)</measure>
    <time_frame>Up to Year 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in glycolipid levels in blood</measure>
    <time_frame>Up to Year 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in glycolipid levels in CSF</measure>
    <time_frame>Up to Year 3</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Gaucher Disease, Type 2</condition>
  <arm_group>
    <arm_group_label>Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>LY3884961</intervention_name>
    <description>Participants will receive a single dose of LY3884961 administered intracisternally.</description>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_label>Low Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylprednisolone</intervention_name>
    <description>Single IV pulse administered as concomitant medication.</description>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_label>Low Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus</intervention_name>
    <description>Loading dose, followed by maintenance doses, followed by dose tapering; administered as concomitant medication.</description>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_label>Low Dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisone</intervention_name>
    <description>Administered orally as concomitant medication, followed by dose tapering.</description>
    <arm_group_label>High Dose</arm_group_label>
    <arm_group_label>Low Dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Bi-allelic GBA1 mutations consistent with a diagnosis of GD2 confirmed by the central&#xD;
             laboratory.&#xD;
&#xD;
          -  Clinical diagnosis of GD2&#xD;
&#xD;
          -  Parent/legal guardian has the ability to understand the purpose and risks of the study&#xD;
             and provide written informed consent and authorization to use protected health&#xD;
             information in accordance with national and local privacy regulations.&#xD;
&#xD;
          -  Patient has a reliable informant (i.e., parent/legal guardian) willing and able to&#xD;
             participate in the study as a source of information on the patient's health status and&#xD;
             cognitive and functional abilities (including providing input into the rating scales).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of a significant CNS disease other than GD2 that may be a cause for the&#xD;
             patient's GD symptoms or may confound study objectives.&#xD;
&#xD;
          -  Achieved independent gait.&#xD;
&#xD;
          -  Severe peripheral symptoms of GD which, in the opinion of the Investigator, would pose&#xD;
             an unacceptable risk to the patient or interfere with the patient's ability to comply&#xD;
             with study procedures or interfere with the conduct of the study.&#xD;
&#xD;
          -  Concomitant disease, condition, or treatment which, in the opinion of the&#xD;
             Investigator, would pose an unacceptable risk to the patient or interfere with the&#xD;
             patient's ability to comply with study procedures or interfere with the conduct of the&#xD;
             study.&#xD;
&#xD;
          -  Use of any GD treatment-related SRT.&#xD;
&#xD;
          -  Use of strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) or P-glycoprotein&#xD;
             (P-gp) medications, herbals, or over-the-counter agents.&#xD;
&#xD;
          -  Any type of prior gene or cell therapy.&#xD;
&#xD;
          -  Live vaccine Immunizations within 4 weeks, or non-live vaccines within 2 weeks prior&#xD;
             to the start of required immunosuppressive regimen.&#xD;
&#xD;
          -  Use of blood thinners. Antiplatelet therapies are acceptable if the patient is&#xD;
             medically able to temporarily stop them from 7 days prior to dosing and through at&#xD;
             least 48 hours after the intracisternal injection and lumbar puncture.&#xD;
&#xD;
          -  Use of systemic immunosuppressant or corticosteroid therapy other than&#xD;
             protocol-specified (topical or inhaled preparations for dermatological conditions or&#xD;
             asthma are allowed).&#xD;
&#xD;
          -  Participation in another investigational drug or device study within the past 3&#xD;
             months.&#xD;
&#xD;
          -  Brain MRI (magnetic resonance imaging) and MRA (magnetic resonance angiography)&#xD;
             showing clinically significant abnormality deemed a contraindication to intracisternal&#xD;
             injection.&#xD;
&#xD;
          -  Clinically significant laboratory test result abnormalities assessed at screening.&#xD;
&#xD;
          -  Contraindications or intolerance to radiographic visualization methods (e.g. MRI, MRA,&#xD;
             CT), and intolerance to contrast agents used for MRI or CT scans.&#xD;
&#xD;
          -  Contraindications to general anesthesia or sedation.&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>0 Months</minimum_age>
    <maximum_age>24 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sarah Neuhaus, D.O.</last_name>
    <role>Study Director</role>
    <affiliation>Prevail Therapeutics</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Prevail Therapeutics</last_name>
    <phone>(917) 336-9310</phone>
    <email>prevail.patients@lilly.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital, 5700 Martin Luther King Jr Way</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jill Nicholas</last_name>
      <phone>510-428-3885</phone>
      <phone_ext>5241</phone_ext>
      <email>jill.nicholas@ucsf.edu</email>
    </contact>
    <contact_backup>
      <last_name>Jenna Fields</last_name>
      <phone>510-428-3885</phone>
      <phone_ext>5156</phone_ext>
      <email>Jenna.Fields@ucsf.edu</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>University of Minnesota Masonic Children's Hospital, 2450 Riverside Avenue</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55454</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carrie Gibson</last_name>
      <phone>612-672-7013</phone>
      <email>Cgibson1@fairview.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Pittsburgh, 4401 Penn Avenue</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dawn Kolar</last_name>
      <email>kolardr@upmc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Manchester Centre for Genomic Medicine, 6th Floor, St Mary's Hospital, Oxford Road</name>
      <address>
        <city>Manchester</city>
        <zip>M13 9WL</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Laura Crowther</last_name>
      <email>laura.crowther@mft.nhs.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>May 11, 2020</study_first_submitted>
  <study_first_submitted_qc>May 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>September 15, 2023</last_update_submitted>
  <last_update_submitted_qc>September 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gaucher Disease</keyword>
  <keyword>GD</keyword>
  <keyword>Gaucher</keyword>
  <keyword>Type 2 Gaucher</keyword>
  <keyword>Neuronopathic Gaucher</keyword>
  <keyword>nGD</keyword>
  <keyword>AAV9</keyword>
  <keyword>GBA</keyword>
  <keyword>Gene Therapy</keyword>
  <keyword>Glucocerebrosidase</keyword>
  <keyword>GBA1 mutation</keyword>
  <keyword>Infants</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gaucher Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sirolimus</mesh_term>
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Methylprednisolone Acetate</mesh_term>
    <mesh_term>Methylprednisolone Hemisuccinate</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Prednisolone acetate</mesh_term>
    <mesh_term>Prednisolone hemisuccinate</mesh_term>
    <mesh_term>Prednisolone phosphate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04411654
org study id: J3Z-MC-OJAB (PRV-GD2-101)
nct id: NCT04411654
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Blinded assessor used in secondary outcome measures
measure: Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events leading to discontinuation
time frame: Year 5
measure: Immunogenicity of AAV9 and GCase in blood
time frame: Up to Year 2
measure: Immunogenicity of AAV9 and GCase in CSF
time frame: Up to Year 3
measure: Time to death
time frame: Baseline until event or study completion, up to Year 5
measure: Time to clinical event
time frame: Baseline until event or study completion, up to Year 5
description: Clinical event defined as tracheostomy/invasive ventilation, and/or percutaneous endoscopic gastrostomy (PEG) tube placement, and/or nasogastric (NG) tube placement
measure: Change in cognitive function
time frame: Months 6, 12 and up to Year 3
description: Measured using Bayley Scales of Infant and Toddler Development (BSID-III)
measure: Change in cognitive function
time frame: Study Month 12 and up to Study Year 3
description: 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)
measure: Change in motor skills
time frame: Months 6, 12 and up to Year 3
description: Change from baseline in motor function using Gross Motor Function Measure (GMFM-88).
measure: Change in motor skills
time frame: Months 6, 12 and up to Year 3
description: Change from baseline in motor function using the BSID-III.
measure: Change in Clinical Global Impressions (Severity)
time frame: Months 6, 12 and up to Year 5
description: Change from baseline in the clinical severity of illness (CGI-Severity {CGI-S}).
measure: Clinical Global Impressions (Improvement)
time frame: Months 6, 12 and up to Year 5
description: Clinical improvement from baseline (CGI-Improvement [CGI-I]).
measure: Change in adaptive behavior and functioning
time frame: Months 6 and 12 and up to Year 3
description: Change from baseline in adaptive functioning using the Vineland Adaptive Behavior Scale (VABS-2) (2nd edition)
measure: Change in most troubling symptoms
time frame: Months 6, 12 and up to Year 5
description: Change from baseline in the Visual Analog Scale for the Most Troubling Symptoms (VAS-MTS)
measure: Change in behavioral symptoms
time frame: Months 6, 12 and up to Year 5
description: Change from baseline in the Child Behavior Checklist (CBCL)
measure: Change in GCase (glucocerebrosidase) enzyme activity levels in blood
time frame: Up to Year 5
measure: Change in GCase enzyme activity levels in CSF (cerebrospinal fluid)
time frame: Up to Year 3
measure: Change in glycolipid levels in blood
time frame: Up to Year 5
measure: Change in glycolipid levels in CSF
time frame: Up to Year 3
arm group label: Low Dose
arm group type: Experimental
arm group label: High Dose
arm group type: Experimental
intervention type: Biological
intervention name: LY3884961
description: Participants will receive a single dose of LY3884961 administered intracisternally.
arm group label: High Dose
arm group label: Low Dose
intervention type: Drug
intervention name: Methylprednisolone
description: Single IV pulse administered as concomitant medication.
arm group label: High Dose
arm group label: Low Dose
intervention type: Drug
intervention name: Sirolimus
description: Loading dose, followed by maintenance doses, followed by dose tapering; administered as concomitant medication.
arm group label: High Dose
arm group label: Low Dose
intervention type: Drug
intervention name: Prednisone
description: Administered orally as concomitant medication, followed by dose tapering.
arm group label: High Dose
arm group label: Low Dose
criteria: 
gender: All
minimum age: 0 Months
maximum age: 24 Months
healthy volunteers: No
last name: Sarah Neuhaus, D.O.
role: Study Director
affiliation: Prevail Therapeutics
last name: Prevail Therapeutics
phone: (917) 336-9310
email: prevail.patients@lilly.com
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Gaucher Disease
mesh term: Sirolimus
mesh term: Prednisone
mesh term: Methylprednisolone
mesh term: Methylprednisolone Acetate
mesh term: Methylprednisolone Hemisuccinate
mesh term: Prednisolone
mesh term: Prednisolone acetate
mesh term: Prednisolone hemisuccinate
mesh term: Prednisolone phosphate
sharing ipd: No