<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/NCT04408625</url>
  </required_header>
  <id_info>
    <org_study_id>PRV-FTD101</org_study_id>
    <nct_id>NCT04408625</nct_id>
  </id_info>
  <brief_title>Phase 1/2 Clinical Trial of PR006 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)</brief_title>
  <acronym>PROCLAIM</acronym>
  <official_title>A Phase 1/2 Ascending Dose Study to Evaluate the Safety and Effects on Progranulin Levels of PR006A in Patients With Fronto-Temporal Dementia With Progranulin Mutations (FTD-GRN)</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>
      Study PRV-FTD101 is a Phase 1/2, multi-center, open-label ascending dose, first-in-human&#xD;
      study that will evaluate the safety and effect of intra-cisternal PR006 administration on&#xD;
      progranulin protein (PGRN) levels in patients with frontotemporal dementia with progranulin&#xD;
      mutations (FTD-GRN). Three escalating dose (low dose, medium dose and high dose) cohorts are&#xD;
      planned. The duration of the study is 5 years. During the first year, patients will be&#xD;
      evaluated for the effect of PR006 on safety, tolerability, immunogenicity, biomarkers, and&#xD;
      efficacy. Patients will follow up for an additional 4 years to monitor safety and changes on&#xD;
      selected biomarkers and clinical outcomes.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 9, 2020</start_date>
  <completion_date type="Anticipated">December 2027</completion_date>
  <primary_completion_date type="Anticipated">December 2027</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>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </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>Sum of adverse reactions (ARs) and suspected ARs</measure>
    <time_frame>5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Sum of serious ARs and serious suspected ARs</measure>
    <time_frame>5 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of procedure or treatment-emergent AEs</measure>
    <time_frame>5 years</time_frame>
    <description>Measured by brain and spine MRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in PGRN immunogenicity in blood</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>PGRN: progranulin protein. Measured by level of antibodies and ELISPOT</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in PGRN immunogenicity in CSF</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>CSF: cerebrospinal fluid</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in AAV9 immunogenicity in blood</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Measured by level of antibodies and ELISPOT.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in AAV9 immunogenicity in CSF</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>Measured by levels of antibodies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in PGRN levels in blood</measure>
    <time_frame>Baseline and 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in PGRN levels in CSF</measure>
    <time_frame>Baseline and 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in CDR plus NACC FTLD</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>CDR: Clinical Dementia Rating staging instrument. NACC FTLD: National Alzheimer's Coordinating Center frontotemporal lobar degeneration domains</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in NfL levels in blood</measure>
    <time_frame>Baseline and 12 months</time_frame>
    <description>NfL: neurofilament light chain</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in NfL levels in CSF</measure>
    <time_frame>Baseline and 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Frontotemporal Dementia</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>Medium 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>PR006</intervention_name>
    <description>Participants will receive a single dose of PR006, administered intra cisterna magna</description>
    <arm_group_label>High dose</arm_group_label>
    <arm_group_label>Low dose</arm_group_label>
    <arm_group_label>Medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylprednisolone</intervention_name>
    <description>1-2 IV pulses administered as concomitant medication</description>
    <arm_group_label>High dose</arm_group_label>
    <arm_group_label>Low dose</arm_group_label>
    <arm_group_label>Medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sirolimus</intervention_name>
    <description>Loading dose, followed by maintenance dose, 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>
    <arm_group_label>Medium 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>
    <arm_group_label>Medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituximab</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>
    <arm_group_label>Medium dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body weight range of ≥40 kg (88 lbs) to ≤110 kg (242 lb) and a BMI of 18 to 34 kg/m2.&#xD;
&#xD;
          -  Has symptomatic frontotemporal dementia (FTD) per investigator assessment.&#xD;
&#xD;
          -  Stable use of background medications at least 8 weeks prior to PR006A dosing.&#xD;
&#xD;
          -  Carrier of a pathogenic GRN (progranulin gene) mutation.&#xD;
&#xD;
          -  Negative screening test for Mycobacterium tuberculosis (MTB) or documented negative&#xD;
             MTB test within 1 year prior to screening.&#xD;
&#xD;
          -  Age- and gender-appropriate cancer screenings are up-to-date.&#xD;
&#xD;
          -  Patient and/or patient's legally authorized representative has the ability to&#xD;
             understand the purpose and risks of the study, and provide written informed consent&#xD;
             and authorization to use protected health information.&#xD;
&#xD;
          -  Patient has a reliable study partner/informant (e.g. family member, friend) willing&#xD;
             and able to participate in the study as a source of information on the patient's&#xD;
             health status and cognitive and functional abilities.&#xD;
&#xD;
          -  Patient is not dependent on a walker or wheelchair.&#xD;
&#xD;
          -  Patient is living in the community (i.e. not in nursing home); some levels of assisted&#xD;
             living may be permitted at the discretion of the investigator.&#xD;
&#xD;
          -  Pneumococcal pneumonia and shingles vaccines are required within 10 years of Screening&#xD;
             (allowed to be performed during Screening but must be given at least 4 weeks prior to&#xD;
             initiation of immunosuppressant regimen).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of a significant CNS (central nervous system) disease other than&#xD;
             frontotemporal dementia (FTD) that may cause FTD symptoms or confound study&#xD;
             objectives.&#xD;
&#xD;
          -  Brain or cervical magnetic resonance image (MRI)/MRA imaging showing clinically&#xD;
             significant abnormality considered to prevent intracisternal injection.&#xD;
&#xD;
          -  Hypersensitivity or contraindications to corticosteroid, rituximab, and/or sirolimus&#xD;
             use.&#xD;
&#xD;
          -  Clinical evidence of peripheral symmetric sensory polyneuropathy (stable sensory&#xD;
             mononeuropathies and radiculopathies are not exclusionary).&#xD;
&#xD;
          -  Concomitant disease or condition within 6 months of screening that could interfere&#xD;
             with, or treatment of which might interfere with, the conduct of the study or that&#xD;
             would, in the opinion of the investigator, pose an unacceptable safety risk to the&#xD;
             patient or interfere with the patient's ability to comply with study procedures&#xD;
&#xD;
          -  Clinically significant laboratory test result abnormalities assessed at screening.&#xD;
&#xD;
          -  Participation within 3 months prior to screening in another therapeutic&#xD;
             investigational drug or device study with purported disease-modifying effects on FTD,&#xD;
             unless it can be documented that the patient received placebo only.&#xD;
&#xD;
          -  Any type of prior gene or cell therapy.&#xD;
&#xD;
          -  Immunizations (live vaccines) in the 4 weeks prior to Screening. Pneumococcal vaccine&#xD;
             and/or shingles vaccine administration is allowed at least 4 weeks prior to initiation&#xD;
             of immunosuppressant regimen.&#xD;
&#xD;
          -  Use of blood thinners in the 2 weeks prior to screening, or anticipated use of blood&#xD;
             thinners during the study. Antiplatelet therapies are acceptable if the patient is&#xD;
             medically able to temporarily stop 48 hours to 7 days (depending on the antiplatelet&#xD;
             medication used) prior to and at least 48 hours after intracisternal injection and&#xD;
             lumbar puncture.&#xD;
&#xD;
          -  Contraindications or intolerance to imaging methods (MRA, MRI, CT) and intolerance to&#xD;
             contrast agents.&#xD;
&#xD;
          -  Contraindications to general anesthesia or deep sedation.&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Olga Uspenskaya-Cadoz, MD, PhD</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>Bioclinica Orlando, 100 West Gore Street, Suite 202</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Poissant</last_name>
      <phone>689-216-3100</phone>
      <email>sarah.poissant@ppd.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital of the University of Pennsylvania, 3 West Gates Building, 3400 Spruce Street</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dahlia Kamel</last_name>
      <phone>215-662-6134</phone>
      <email>kamel.dahlia@pennmedicine.upenn.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital, Brain &amp; Mind Research Institute, 94 Mallet Street</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cassandra Kaizik</last_name>
      <phone>02 9515 4540</phone>
      <email>cassandra.kaizik@sydney.edu.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>UZ Leuven, Neurologie Herestraat 49</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carine Schildermans</last_name>
      <phone>3126345500</phone>
      <email>carine.schildermans@uzleuven.be</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic de Barcelona, Villaroel 170 Servicio de Neurología</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Beatriz Bosch Capdevila, PhD</last_name>
      <phone>[+34] 934518240</phone>
      <phone_ext>3088</phone_ext>
      <email>beabc6@hotmail.com/bbosch@clinic.cat</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Donostia, Servicio De Neurologia, Consultas Externas Neurologia, San Sebastian, Guipúzcoa</name>
      <address>
        <city>San Sebastian</city>
        <zip>20014</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fermin Moreno</last_name>
      <phone>+39 443007027</phone>
      <email>fermin.morenoizco@osakidetza.eus</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University College London,Queen Square, Dementia Research Building, London,</name>
      <address>
        <city>London</city>
        <zip>WC1N 3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Miguel Alvarez</last_name>
      <email>miguel.alvarez.13@ucl.ac.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>April 5, 2023</last_update_submitted>
  <last_update_submitted_qc>April 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Fronto-Temporal Dementia</keyword>
  <keyword>Frontotemporal Dementia</keyword>
  <keyword>Progranulin Mutations</keyword>
  <keyword>FTD-GRN</keyword>
  <keyword>Gene Therapy</keyword>
  <keyword>Dementia Gene Therapy</keyword>
  <keyword>AAV9</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dementia</mesh_term>
    <mesh_term>Frontotemporal Dementia</mesh_term>
    <mesh_term>Aphasia, Primary Progressive</mesh_term>
    <mesh_term>Pick Disease of the Brain</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>Rituximab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04408625
org study id: PRV-FTD101
nct id: NCT04408625
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Study PRV-FTD101 is a Phase 1/2, multi-center, open-label ascending dose, first-in-human
      study that will evaluate the safety and effect of intra-cisternal PR006 administration on
      progranulin protein (PGRN) levels in patients with frontotemporal dementia with progranulin
      mutations (FTD-GRN). Three escalating dose (low dose, medium dose and high dose) cohorts are
      planned. The duration of the study is 5 years. During the first year, patients will be
      evaluated for the effect of PR006 on safety, tolerability, immunogenicity, biomarkers, and
      efficacy. Patients will follow up for an additional 4 years to monitor safety and changes on
      selected biomarkers and clinical outcomes.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events Leading to discontinuation
time frame: Year 5
measure: Sum of adverse reactions (ARs) and suspected ARs
time frame: 5 years
measure: Sum of serious ARs and serious suspected ARs
time frame: 5 years
measure: Incidence of procedure or treatment-emergent AEs
time frame: 5 years
description: Measured by brain and spine MRI
measure: Change in PGRN immunogenicity in blood
time frame: Baseline and 12 months
description: PGRN: progranulin protein. Measured by level of antibodies and ELISPOT
measure: Change in PGRN immunogenicity in CSF
time frame: Baseline and 12 months
description: CSF: cerebrospinal fluid
measure: Change in AAV9 immunogenicity in blood
time frame: Baseline and 12 months
description: Measured by level of antibodies and ELISPOT.
measure: Change in AAV9 immunogenicity in CSF
time frame: Baseline and 12 months
description: Measured by levels of antibodies.
measure: Change in PGRN levels in blood
time frame: Baseline and 12 months
measure: Change in PGRN levels in CSF
time frame: Baseline and 12 months
measure: Change in CDR plus NACC FTLD
time frame: Baseline and 12 months
description: CDR: Clinical Dementia Rating staging instrument. NACC FTLD: National Alzheimer's Coordinating Center frontotemporal lobar degeneration domains
measure: Change in NfL levels in blood
time frame: Baseline and 12 months
description: NfL: neurofilament light chain
measure: Change in NfL levels in CSF
time frame: Baseline and 12 months
arm group label: Low dose
arm group type: Experimental
arm group label: Medium dose
arm group type: Experimental
arm group label: High dose
arm group type: Experimental
intervention type: Biological
intervention name: PR006
description: Participants will receive a single dose of PR006, administered intra cisterna magna
arm group label: High dose
arm group label: Low dose
arm group label: Medium dose
intervention type: Drug
intervention name: Methylprednisolone
description: 1-2 IV pulses administered as concomitant medication
arm group label: High dose
arm group label: Low dose
arm group label: Medium dose
intervention type: Drug
intervention name: Sirolimus
description: Loading dose, followed by maintenance dose, followed by dose tapering; administered as concomitant medication
arm group label: High dose
arm group label: Low dose
arm group label: Medium 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
arm group label: Medium dose
intervention type: Drug
intervention name: Rituximab
description: Single IV pulse administered as concomitant medication.
arm group label: High dose
arm group label: Low dose
arm group label: Medium dose
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: No
last name: Olga Uspenskaya-Cadoz, MD, PhD
role: Study Director
affiliation: Prevail Therapeutics
last name: Prevail Therapeutics
phone: (917) 336-9310
email: prevail.patients@lilly.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Australia
country: Belgium
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Dementia
mesh term: Frontotemporal Dementia
mesh term: Aphasia, Primary Progressive
mesh term: Pick Disease of the Brain
mesh term: Sirolimus
mesh term: Prednisone
mesh term: Methylprednisolone
mesh term: Rituximab