<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/NCT03008161</url>
  </required_header>
  <id_info>
    <org_study_id>NPT088-CL002</org_study_id>
    <nct_id>NCT03008161</nct_id>
  </id_info>
  <brief_title>Multiple Dose Safety Study of NPT088 in Patients With Mild to Moderate Probable Alzheimer's Disease</brief_title>
  <official_title>A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose Escalation Study of NPT088 in Patients With Probable Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Proclara Biosciences, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Alzheimer's Association</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Proclara Biosciences, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the safety and tolerability of multiple doses of&#xD;
      NPT088 in patients with mild to moderate probable Alzheimer's Disease. The study will also&#xD;
      evaluate the pharmacokinetics, immunogenicity and exploratory pharmacodynamic characteristics&#xD;
      of multiple doses of NPT088.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a multicenter Phase 1, randomized, double-blind, placebo-controlled,&#xD;
      multiple-dose, dose-escalation safety and tolerability study of NPT088 or placebo in patients&#xD;
      with Probable AD with a MMSE score of 16-27. Enrolled patients will receive an intravenous&#xD;
      infusion of NPT088 or placebo once a month for six months during this study. Four dose&#xD;
      cohorts are planned with the first two cohorts enrolling 9 patients each (6 NPT088: 3&#xD;
      placebo) and the final two cohorts enrolling 24 patients each (16 NPT088: 8 placebo) for a&#xD;
      total of 66 patients (44 NPT088: 22 placebo).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">February 6, 2019</completion_date>
  <primary_completion_date type="Actual">February 6, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Baseline to Week 32</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Multiple dose pharmacokinetic (PK) serum concentrations of NPT088</measure>
    <time_frame>Up to Week 32</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple dose PK CSF concentrations of NPT088</measure>
    <time_frame>Up to Week 32</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple dose immunogenicity of NPT088</measure>
    <time_frame>Up to Week 32</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Change from baseline in florbetapir-fluorine-18 positron emission tomography (PET) imaging in certain brain areas</measure>
    <time_frame>Baseline and Week 24</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change from baseline in [18F] MNI-960 PET imaging in certain brain areas</measure>
    <time_frame>Baseline and Week 24</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in CSF or blood biomarkers</measure>
    <time_frame>Up to Week 32</time_frame>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">83</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive monthly IV infusions of either low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive monthly IV infusions of either mid-low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive monthly IV infusions of either mid-high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive monthly IV infusions of either high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NPT088</intervention_name>
    <description>IgG1 Fc-GAIM fusion protein, a recombinant fusion protein</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <other_name>IgG1</other_name>
    <other_name>fusion protein</other_name>
    <other_name>GAIM</other_name>
    <other_name>anti-Abeta</other_name>
    <other_name>anti-Tau</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria: For enrollment in the study, participants must&#xD;
&#xD;
          -  be between 50 and 85 years of age, inclusive&#xD;
&#xD;
          -  have a Mini Mental State Examination (MMSE) scores between 16-27 (inclusive)&#xD;
&#xD;
          -  have a Modified Hachinski Score of less than or equal to 4&#xD;
&#xD;
          -  have a diagnosis of Probable Alzheimer's Disease (AD) according to consensus criteria&#xD;
             defined by the National Institute on Aging-Alzheimer's Association work group&#xD;
&#xD;
          -  have a Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0, with the memory box score&#xD;
             equal to or greater than 0.5&#xD;
&#xD;
          -  have a positive florbetapir positron emission tomography (PET) amyloid scan&#xD;
&#xD;
          -  consent to apolipoprotein E (ApoE) genotyping&#xD;
&#xD;
          -  be willing to undergo repeat Magnetic Resonance Imaging (MRI) and PET imaging&#xD;
&#xD;
          -  be on stable doses of allowed medications for at least 30 days prior to Screening.&#xD;
             Concurrent treatment with cholinesterase inhibitors and/or memantine is allowed&#xD;
&#xD;
          -  be in good healthy apart from the clinical diagnosis of AD&#xD;
&#xD;
          -  have a dedicated Caregiver who provides care at least 4 hours a day for 4 days a week&#xD;
             and will provide informed consent for their participation&#xD;
&#xD;
        Exclusion Criteria: For enrollment in the study, participants must NOT:&#xD;
&#xD;
          -  have a history of, or screening MRI indicative of any significant brain abnormality&#xD;
&#xD;
          -  have any major medical illness or unstable medical condition or in the opinion of the&#xD;
             Investigator have any reason that may interfere with the participants ability to&#xD;
             comply with the study procedures and abide by study restrictions or with the ability&#xD;
             to interpret safety data&#xD;
&#xD;
          -  reside in a nursing home or need 24-hour care and supervision&#xD;
&#xD;
          -  take excluded medications&#xD;
&#xD;
          -  have exclusionary values on the Screening blood and urine sample&#xD;
&#xD;
          -  have been treated with immunomodulators to treat AD&#xD;
&#xD;
          -  have participated in an investigational drug or device study within 90 days&#xD;
&#xD;
          -  have a known allergy to study drug&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Proclara Biosciences</last_name>
    <role>Study Director</role>
    <affiliation>Proclara</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ATP Clinical Research, Inc.</name>
      <address>
        <city>Costa Mesa</city>
        <state>California</state>
        <zip>92626</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurology Center of North Orange County</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative Neuroscience Network</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern California Research</name>
      <address>
        <city>Simi Valley</city>
        <state>California</state>
        <zip>93065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Associated Neurologists of Southern Connecticut</name>
      <address>
        <city>Fairfield</city>
        <state>Connecticut</state>
        <zip>06824</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JEM Research Institute</name>
      <address>
        <city>Atlantis</city>
        <state>Florida</state>
        <zip>33462</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indago Research and Health Center</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alzheimer's Research and Treatment Center</name>
      <address>
        <city>Lake Worth</city>
        <state>Florida</state>
        <zip>33449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Miami Jewish Health Systems</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33137</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Research Group of Central Florida</name>
      <address>
        <city>Orange City</city>
        <state>Florida</state>
        <zip>32763</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compass Research</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Progressive Medical Research</name>
      <address>
        <city>Port Orange</city>
        <state>Florida</state>
        <zip>32137</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Axiom Clinical Research</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compass-The Villages</name>
      <address>
        <city>The Villages</city>
        <state>Florida</state>
        <zip>32162</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Research and Health Education Foundation</name>
      <address>
        <city>Columbus</city>
        <state>Georgia</state>
        <zip>31909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NeuroStudies LLC</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princeton Medical Institute</name>
      <address>
        <city>Princeton</city>
        <state>New Jersey</state>
        <zip>08540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurological Associates of Albany</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Integrative Clinical Trials, Inc.</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alzheimer's Memory Center</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28270</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lehigh Center for Clinical Research</name>
      <address>
        <city>Allentown</city>
        <state>Pennsylvania</state>
        <zip>18104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Abington Neurological Associates, Ltd</name>
      <address>
        <city>Willow Grove</city>
        <state>Pennsylvania</state>
        <zip>19090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Neurology Clinic, PC</name>
      <address>
        <city>Cordova</city>
        <state>Tennessee</state>
        <zip>38018</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Krishnan R, Tsubery H, Proschitsky MY, Asp E, Lulu M, Gilead S, Gartner M, Waltho JP, Davis PJ, Hounslow AM, Kirschner DA, Inouye H, Myszka DG, Wright J, Solomon B, Fisher RA. A bacteriophage capsid protein provides a general amyloid interaction motif (GAIM) that binds and remodels misfolded protein assemblies. J Mol Biol. 2014 Jun 26;426(13):2500-19. doi: 10.1016/j.jmb.2014.04.015. Epub 2014 Apr 22.</citation>
    <PMID>24768993</PMID>
  </reference>
  <reference>
    <citation>Levenson JM, Schroeter S, Carroll JC, Cullen V, Asp E, Proschitsky M, Chung CH, Gilead S, Nadeem M, Dodiya HB, Shoaga S, Mufson EJ, Tsubery H, Krishnan R, Wright J, Solomon B, Fisher R, Gannon KS. NPT088 reduces both amyloid-beta and tau pathologies in transgenic mice. Alzheimers Dement (N Y). 2016 Jul 14;2(3):141-155. doi: 10.1016/j.trci.2016.06.004. eCollection 2016 Sep.</citation>
    <PMID>29067301</PMID>
  </reference>
  <reference>
    <citation>Krishnan R, Hefti F, Tsubery H, Lulu M, Proschitsky M, Fisher R. Conformation as the Therapeutic Target for Neurodegenerative Diseases. Curr Alzheimer Res. 2017;14(4):393-402. doi: 10.2174/1567205014666170116152622.</citation>
    <PMID>28093972</PMID>
  </reference>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>December 23, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>August 14, 2019</last_update_submitted>
  <last_update_submitted_qc>August 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GAIM</keyword>
  <keyword>amyloid</keyword>
  <keyword>anti-aBeta</keyword>
  <keyword>anti-tau</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03008161
org study id: NPT088-CL002
nct id: NCT03008161
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of the study is to evaluate the safety and tolerability of multiple doses of
      NPT088 in patients with mild to moderate probable Alzheimer's Disease. The study will also
      evaluate the pharmacokinetics, immunogenicity and exploratory pharmacodynamic characteristics
      of multiple doses of NPT088.
This study is a multicenter Phase 1, randomized, double-blind, placebo-controlled,
      multiple-dose, dose-escalation safety and tolerability study of NPT088 or placebo in patients
      with Probable AD with a MMSE score of 16-27. Enrolled patients will receive an intravenous
      infusion of NPT088 or placebo once a month for six months during this study. Four dose
      cohorts are planned with the first two cohorts enrolling 9 patients each (6 NPT088: 3
      placebo) and the final two cohorts enrolling 24 patients each (16 NPT088: 8 placebo) for a
      total of 66 patients (44 NPT088: 22 placebo).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of patients with adverse events
time frame: Baseline to Week 32
measure: Multiple dose pharmacokinetic (PK) serum concentrations of NPT088
time frame: Up to Week 32
measure: Multiple dose PK CSF concentrations of NPT088
time frame: Up to Week 32
measure: Multiple dose immunogenicity of NPT088
time frame: Up to Week 32
measure: Change from baseline in florbetapir-fluorine-18 positron emission tomography (PET) imaging in certain brain areas
time frame: Baseline and Week 24
measure: Change from baseline in [18F] MNI-960 PET imaging in certain brain areas
time frame: Baseline and Week 24
measure: Change in CSF or blood biomarkers
time frame: Up to Week 32
arm group label: Cohort 1
arm group type: Experimental
description: Participants will receive monthly IV infusions of either low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months
arm group label: Cohort 2
arm group type: Experimental
description: Participants will receive monthly IV infusions of either mid-low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months
arm group label: Cohort 3
arm group type: Experimental
description: Participants will receive monthly IV infusions of either mid-high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months
arm group label: Cohort 4
arm group type: Experimental
description: Participants will receive monthly IV infusions of either high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months
intervention type: Drug
intervention name: NPT088
description: IgG1 Fc-GAIM fusion protein, a recombinant fusion protein
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
other name: IgG1
other name: fusion protein
other name: GAIM
other name: anti-Abeta
other name: anti-Tau
intervention type: Drug
intervention name: Placebo
description: Placebo
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3
arm group label: Cohort 4
criteria: 
gender: All
minimum age: 50 Years
maximum age: 85 Years
healthy volunteers: No
last name: Proclara Biosciences
role: Study Director
affiliation: Proclara
facility: 
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country: United States
citation: Krishnan R, Tsubery H, Proschitsky MY, Asp E, Lulu M, Gilead S, Gartner M, Waltho JP, Davis PJ, Hounslow AM, Kirschner DA, Inouye H, Myszka DG, Wright J, Solomon B, Fisher RA. A bacteriophage capsid protein provides a general amyloid interaction motif (GAIM) that binds and remodels misfolded protein assemblies. J Mol Biol. 2014 Jun 26;426(13):2500-19. doi: 10.1016/j.jmb.2014.04.015. Epub 2014 Apr 22.
PMID: 24768993
citation: Levenson JM, Schroeter S, Carroll JC, Cullen V, Asp E, Proschitsky M, Chung CH, Gilead S, Nadeem M, Dodiya HB, Shoaga S, Mufson EJ, Tsubery H, Krishnan R, Wright J, Solomon B, Fisher R, Gannon KS. NPT088 reduces both amyloid-beta and tau pathologies in transgenic mice. Alzheimers Dement (N Y). 2016 Jul 14;2(3):141-155. doi: 10.1016/j.trci.2016.06.004. eCollection 2016 Sep.
PMID: 29067301
citation: Krishnan R, Hefti F, Tsubery H, Lulu M, Proschitsky M, Fisher R. Conformation as the Therapeutic Target for Neurodegenerative Diseases. Curr Alzheimer Res. 2017;14(4):393-402. doi: 10.2174/1567205014666170116152622.
PMID: 28093972
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: Undecided