xml: <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/NCT05974579</url>
    </required_header>
    <id_info>
      <org_study_id>2024-5148</org_study_id>
      <secondary_id>2024-5148</secondary_id>
      <nct_id>NCT05974579</nct_id>
    </id_info>
    <brief_title>Safety and Dosimetry of a New Radiotracer to Detect Misfolded SOD1 Associated With Amyotrophic Lateral Sclerosis</brief_title>
    <official_title>A Single Center, Open Label Study to Evaluate Biodistribution, Pharmacokinetics and Safety of [89Zr]Zr-DFO-AP-101 PET (Positron Emission Tomography) in Healthy Volunteers and Amyotrophic Lateral Sclerosis (ALS) Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Université de Sherbrooke</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Eli Lilly and Company</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Chorus Wellness Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>AL-S Pharma AG</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Université de Sherbrooke</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare&#xD;
        neurodegenerative disease resulting in loss, primarily, of the motor neurons in the motor&#xD;
        cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in the US.&#xD;
  &#xD;
        Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and significant&#xD;
        disease progression before formal diagnosis. An imaging test for early detection of ALS and&#xD;
        for monitoring disease progression would have significant diagnostic and prognostic value.&#xD;
  &#xD;
        PET imaging with an appropriate radiotracer has great potential as a biomarker for ALS given&#xD;
        that it would permit visualization of central nervous system (CNS) pathology in individuals&#xD;
        living with the disease.&#xD;
  &#xD;
        To that extent, the primary goal of this phase I study is evaluating the safety and&#xD;
        biodistribution of the new tracer [89Zr]Zr-DFO-AP-101 in healthy volunteers and ALS patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a&#xD;
        rare neurodegenerative disease resulting in loss, primarily, of the motor neurons in the&#xD;
        motor cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in&#xD;
        the US. Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and&#xD;
        significant disease progression before formal diagnosis.&#xD;
  &#xD;
        Design: This is a phase I clinical trial and a 2-part, single center, open label study in&#xD;
        healthy volunteers (Part A) and confirmed ALS patients (Part B). The primary goal is&#xD;
        evaluating the safety and biodistribution of the radiotracer [89Zr]Zr-DFO-AP-101 in healthy&#xD;
        volunteers and ALS patients via PET/CT imaging.&#xD;
  &#xD;
        Objectives: The primary objectives of this study are:&#xD;
  &#xD;
        (Part A) To evaluate, by PET imaging, the safety, biodistribution and dosimetry of&#xD;
        [89Zr]Zr-DFO-AP-101 in healthy men and women and in ALS patients&#xD;
  &#xD;
        Intervention and Follow-up: Following a screening visit, eligible participants will come to&#xD;
        the research center for all study assessments.&#xD;
  &#xD;
          -  On Day 0, a single intravenous dose of [89Zr]Zr-DFO-AP-101 40 MBq will be administrated&#xD;
             and a 45 min whole body PET/CT acquisition will be performed at two hours post&#xD;
             injection. Physical exam, ECG, vital signs and blood/urine samples will be collected.&#xD;
  &#xD;
          -  Further PET acquisitions and same data/samples collection will be repeated at days 1, 3,&#xD;
             7 and 10 post-injection.&#xD;
  &#xD;
          -  Participants will be contacted for a final follow-up visit approximately 14 days after&#xD;
             injection.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">July 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">May 31, 2024</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Two groups will be enrolled: 8 healthy subjects and 4 patients with ALS This is non-randomized, all participants will receive the same dose of radiotracer</intervention_model_description>
      <primary_purpose>Diagnostic</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of adverse events (AEs) and serious adverse events (SAEs)</measure>
      <time_frame>day 0 (post-injection) to day 14 (end of study)</time_frame>
      <description>Number of adverse events (AEs) and serious adverse events following administration of [89Zr]Zr-DFO-AP-101 that are new or worsened (compared to baseline/pre-dose)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Biodistribution of [89Zr]Zr-DFO-AP-101</measure>
      <time_frame>Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose</time_frame>
      <description>Assessed by whole-body PET imaging</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dosimetry of [89Zr]Zr-DFO-AP-101 in human</measure>
      <time_frame>Pre-Dose and at 2 hours, 1, 3, 7, 10 days post-dose</time_frame>
      <description>Organ activity concentration (in liver, kidneys, blood, spleen, ...) measured by drawing region of interests on the PET images.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cmax</measure>
      <time_frame>Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose</time_frame>
      <description>Maximal concentration of [89Zr]Zr-DFO-AP-101 in plasma over time after injection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the curve (AUC)</measure>
      <time_frame>Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose</time_frame>
      <description>AUC of [89Zr]Zr-DFO-AP-101 in plasma over time after injection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>residence time</measure>
      <time_frame>Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose</time_frame>
      <description>Time (1/2) of residence of [89Zr]Zr-DFO-AP-101 in plasma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Excretion</measure>
      <time_frame>Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose</time_frame>
      <description>Concentration of [89Zr]Zr-DFO-AP-101 urine over time</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Differential labeling and uptake</measure>
      <time_frame>Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose</time_frame>
      <description>Assessment of target organ/tissue ratio in ALS patients versus healthy volunteers</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">12</enrollment>
    <condition>Amyotrophic Lateral Sclerosis</condition>
    <arm_group>
      <arm_group_label>Healthy participants</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Patients with ALS</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>89Zr-DFO-AP-101</intervention_name>
      <description>At Day 0, patients will receive one dose of the radiotracer. A PET/CT scan will be done pre- and 2h post-dose.&#xD;
  At 1, 3, 7 and 10 days post-dose, a PET/CT scan will be repeated.</description>
      <arm_group_label>Healthy participants</arm_group_label>
      <arm_group_label>Patients with ALS</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Aged of:&#xD;
  &#xD;
                 1. For healthy participants: Male or female subjects aged 50 years or older&#xD;
  &#xD;
                 2. For ALS patients: Male or female subjects aged 18 years and older&#xD;
  &#xD;
            2. Able to remain in a lying position for up to 45 minutes without respiratory support.&#xD;
  &#xD;
            3. A) For ALS patients, confirmed diagnostic of definitive ALS according to El-Escorial&#xD;
               criteria14 B) for healthy participants: no neurologic condition (confirmed by physical&#xD;
               exam)&#xD;
  &#xD;
            4. Have venous access sufficient to allow for blood sampling&#xD;
  &#xD;
            5. Are reliable and willing to make themselves available for the duration of the study&#xD;
               and are willing to follow CRCHUS-specific study procedures.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Are currently enrolled or were enrolled in the last 12 weeks in any other clinical&#xD;
               trial involving a study drug or off label use of a drug or device, or any other type&#xD;
               of medical research judged not to be scientifically or medically compatible with this&#xD;
               study.&#xD;
  &#xD;
            2. Female participants who are pregnant or breast feeding; or women of childbearing&#xD;
               potential (&lt;50 years old) and men who are sexually active who are not willing to use&#xD;
               an accepted effective contraceptive method.&#xD;
  &#xD;
            3. Plan to have surgery or other invasive procedure during the course of the study (up to&#xD;
               14 days post-injection)&#xD;
  &#xD;
            4. Have a progressive medical illness including, but not limited to, any cardiovascular,&#xD;
               hepatic, respiratory, hematological, endocrine, psychiatric or neurological disease,&#xD;
               convulsions, or any clinically significant laboratory abnormality at screening and at&#xD;
               first visit (D0) that, in the judgment of the medical doctor, indicate a medical&#xD;
               problem that would preclude study participation.&#xD;
  &#xD;
            5. Have one of these conditions (for both patient groups):&#xD;
  &#xD;
                 1. hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities&#xD;
                    (ALT or AST ≥3 × ULN or total bilirubin ≥2 × ULN) and hematology abnormalities at&#xD;
                    screening.&#xD;
  &#xD;
                 2. severe chronic kidney disease (eg, an estimated glomerular filtration rate [eGFR]&#xD;
                    &lt;30 mL/min/1.73m or requires chronic dialysis) at screening.&#xD;
  &#xD;
                 3. Have severe active psychiatric illness.&#xD;
  &#xD;
                 4. Have a diagnosis of another neurodegenerative disease (e.g. Parkinson disease,&#xD;
                    Alzheimer's disease, etc).&#xD;
  &#xD;
                 5. Have a significant infection or known inflammatory process on screening or at Day&#xD;
                    0.&#xD;
  &#xD;
                 6. Alcohol or drug abuse based on patient auto-report&#xD;
  &#xD;
                 7. Have a history of relevant atopy or drug hypersensitivity or allergy to&#xD;
                    antibodies;&#xD;
  &#xD;
                 8. Have an abnormal blood pressure (supine) defined as a diastolic blood pressure&#xD;
                    &gt;90 or &lt;45 mmHg and/or a systolic blood pressure &gt;160 or &lt;90 mmHg. Re-testing may&#xD;
                    occur once during the screening visit within 2 hours of the initial abnormal&#xD;
                    blood pressure measurement at the discretion of the investigator.&#xD;
  &#xD;
            6. For ALS patients:&#xD;
  &#xD;
                 1. Have undergone a tracheostomy for ALS symptoms.&#xD;
  &#xD;
                 2. Are on nasal intermittent positive pressure ventilation (NIPPV) &gt;4h during the&#xD;
                    day, while awake for the treatment of ALS related symptoms.&#xD;
  &#xD;
                 3. Have other causes of neuromuscular weakness.&#xD;
  &#xD;
            7. Have received treatment with biologic agents (such as monoclonal antibodies, including&#xD;
               marketed drugs and AP-101) within 3 months or 5 half-lives (whichever is longer) prior&#xD;
               to study drug injection.&#xD;
  &#xD;
            8. Have received any blood or blood products within the 3 months prior to screening.&#xD;
  &#xD;
            9. Cannot communicate reliably with the investigator.&#xD;
  &#xD;
           10. Are unwilling or unable to give written informed consent.&#xD;
  &#xD;
           11. In the opinion of the medical doctor or his/her delegate, are unsuitable for inclusion&#xD;
               in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Eric E Turcotte, MD</last_name>
      <role>Study Director</role>
      <affiliation>Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Brigitte Guérin, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Amelie Tetu, MSc</last_name>
      <phone>819-346-1110</phone>
      <email>amelie.tetu.ciussse-chus@ssss.gouv.qc.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Sarah Côté-Bigras, MSc</last_name>
      <phone>819-346-1110</phone>
      <email>sarah.cote-bigras.ciussse-chus@ssss.gouv.qc.ca</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>July 26, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 3, 2023</study_first_posted>
    <last_update_submitted>July 26, 2023</last_update_submitted>
    <last_update_submitted_qc>July 26, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 3, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>PET imaging</keyword>
    <keyword>CT imaging</keyword>
    <keyword>AP-101</keyword>
    <keyword>89-Zirconium</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Motor Neuron Disease</mesh_term>
      <mesh_term>Amyotrophic Lateral Sclerosis</mesh_term>
      <mesh_term>Sclerosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05974579
  org study id: 2024-5148
  secondary id: 2024-5148
  nct id: NCT05974579
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a rare
        neurodegenerative disease resulting in loss, primarily, of the motor neurons in the motor
        cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in the US.
  
        Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and significant
        disease progression before formal diagnosis. An imaging test for early detection of ALS and
        for monitoring disease progression would have significant diagnostic and prognostic value.
  
        PET imaging with an appropriate radiotracer has great potential as a biomarker for ALS given
        that it would permit visualization of central nervous system (CNS) pathology in individuals
        living with the disease.
  
        To that extent, the primary goal of this phase I study is evaluating the safety and
        biodistribution of the new tracer [89Zr]Zr-DFO-AP-101 in healthy volunteers and ALS patients.
  Background: Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, is a
        rare neurodegenerative disease resulting in loss, primarily, of the motor neurons in the
        motor cortex, brainstem and spinal cord. It currently affects 3 of every 100,000 people in
        the US. Currently, there is no diagnostic tool for ALS, resulting in misdiagnosis and
        significant disease progression before formal diagnosis.
  
        Design: This is a phase I clinical trial and a 2-part, single center, open label study in
        healthy volunteers (Part A) and confirmed ALS patients (Part B). The primary goal is
        evaluating the safety and biodistribution of the radiotracer [89Zr]Zr-DFO-AP-101 in healthy
        volunteers and ALS patients via PET/CT imaging.
  
        Objectives: The primary objectives of this study are:
  
        (Part A) To evaluate, by PET imaging, the safety, biodistribution and dosimetry of
        [89Zr]Zr-DFO-AP-101 in healthy men and women and in ALS patients
  
        Intervention and Follow-up: Following a screening visit, eligible participants will come to
        the research center for all study assessments.
  
          -  On Day 0, a single intravenous dose of [89Zr]Zr-DFO-AP-101 40 MBq will be administrated
             and a 45 min whole body PET/CT acquisition will be performed at two hours post
             injection. Physical exam, ECG, vital signs and blood/urine samples will be collected.
  
          -  Further PET acquisitions and same data/samples collection will be repeated at days 1, 3,
             7 and 10 post-injection.
  
          -  Participants will be contacted for a final follow-up visit approximately 14 days after
             injection.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: Two groups will be enrolled: 8 healthy subjects and 4 patients with ALS This is non-randomized, all participants will receive the same dose of radiotracer
  primary purpose: Diagnostic
  masking: None (Open Label)
  measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
  time frame: day 0 (post-injection) to day 14 (end of study)
  description: Number of adverse events (AEs) and serious adverse events following administration of [89Zr]Zr-DFO-AP-101 that are new or worsened (compared to baseline/pre-dose)
  measure: Biodistribution of [89Zr]Zr-DFO-AP-101
  time frame: Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
  description: Assessed by whole-body PET imaging
  measure: Dosimetry of [89Zr]Zr-DFO-AP-101 in human
  time frame: Pre-Dose and at 2 hours, 1, 3, 7, 10 days post-dose
  description: Organ activity concentration (in liver, kidneys, blood, spleen, ...) measured by drawing region of interests on the PET images.
  measure: Cmax
  time frame: Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
  description: Maximal concentration of [89Zr]Zr-DFO-AP-101 in plasma over time after injection
  measure: Area under the curve (AUC)
  time frame: Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
  description: AUC of [89Zr]Zr-DFO-AP-101 in plasma over time after injection
  measure: residence time
  time frame: Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
  description: Time (1/2) of residence of [89Zr]Zr-DFO-AP-101 in plasma
  measure: Excretion
  time frame: Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
  description: Concentration of [89Zr]Zr-DFO-AP-101 urine over time
  measure: Differential labeling and uptake
  time frame: Pre-dose and at 2 hours, 1, 3, 7, 10 days post-dose
  description: Assessment of target organ/tissue ratio in ALS patients versus healthy volunteers
  arm group label: Healthy participants
  arm group type: Experimental
  description: Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.
  arm group label: Patients with ALS
  arm group type: Experimental
  description: Will receive 40MBq of 89Zr-DFO-AP-101, once, at Day 0.
  intervention type: Drug
  intervention name: 89Zr-DFO-AP-101
  description: At Day 0, patients will receive one dose of the radiotracer. A PET/CT scan will be done pre- and 2h post-dose.
  At 1, 3, 7 and 10 days post-dose, a PET/CT scan will be repeated.
  arm group label: Healthy participants
  arm group label: Patients with ALS
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Eric E Turcotte, MD
  role: Study Director
  affiliation: Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke
  last name: Brigitte Guérin, PhD
  role: Principal Investigator
  affiliation: Estrie University Integrated Health and Social Services Center - University Hospital of Sherbrooke
  last name: Amelie Tetu, MSc
  phone: 819-346-1110
  email: amelie.tetu.ciussse-chus@ssss.gouv.qc.ca
  last name: Sarah Côté-Bigras, MSc
  phone: 819-346-1110
  email: sarah.cote-bigras.ciussse-chus@ssss.gouv.qc.ca
  responsible party type: Sponsor
  mesh term: Motor Neuron Disease
  mesh term: Amyotrophic Lateral Sclerosis
  mesh term: Sclerosis
  sharing ipd: No