<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/NCT03764488</url>
  </required_header>
  <id_info>
    <org_study_id>233HV101</org_study_id>
    <nct_id>NCT03764488</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Safety, Tolerability, and Distribution of a Microdose of Radiolabeled BIIB067 (99mTc-MAG3-BIIB067) Co-administered With BIIB067 (Tofersen) to Healthy Adults</brief_title>
  <official_title>A Phase 1, Safety, Tolerability, and Distribution Study of a Microdose of Radiolabeled BIIB067 Co-administered With BIIB067 to Healthy Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Biogen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Biogen</source>
  <oversight_info>
    <has_dmc>No</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>
      The primary objective of the study is to evaluate the distribution in the central nervous&#xD;
      system (CNS) of a microdose 99mTc-MAG3-BIIB067 co-administered with unlabeled BIIB067&#xD;
      (Tofersen). The secondary objective of the study is to assess the safety and tolerability of&#xD;
      unlabeled BIIB067 co-administered with a microdose of 99mTc-MAG3-BIIB067 to healthy&#xD;
      participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2018</start_date>
  <completion_date type="Actual">July 10, 2021</completion_date>
  <primary_completion_date type="Actual">June 10, 2021</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>Sequential Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>BIIB067 Concentrations Throughout the CNS</measure>
    <time_frame>1 to 24 hours post-dose on Day 1</time_frame>
    <description>BIIB067 concentrations throughout the CNS will be estimated by single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of 99mTc-MAG3-BIIB067.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Up to Day 91</time_frame>
    <description>An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose of Radiation Absorbed (Dosimetry) in Specific Regions of the CNS</measure>
    <time_frame>1 to 24 hours post-dose on Day 1</time_frame>
    <description>Dose of radiation absorbed (dosimetry) in specific regions of the CNS will be estimated by SPECT/CT imaging of 99mTc-MAG3-BIIB067.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 15 milliliter (mL) artificial cerebrospinal fluid (aCSF).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 15 mL aCSF.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 5 mL aCSF.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in up to 20 mL aCSF.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tofersen</intervention_name>
    <description>Administered as specified in the treatment arm.</description>
    <arm_group_label>BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF</arm_group_label>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF</arm_group_label>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF</arm_group_label>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF</arm_group_label>
    <other_name>BIIB067</other_name>
    <other_name>QALSODY</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>99mTc-MAG3-BIIB067</intervention_name>
    <description>Administered as specified in the treatment arm.</description>
    <arm_group_label>BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF</arm_group_label>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF</arm_group_label>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF</arm_group_label>
    <arm_group_label>BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Must have a body mass index between 18 and 30 kilogram per square meter (kg/m^2),&#xD;
             inclusive.&#xD;
&#xD;
          -  All men must practice highly effective contraception during the study and for 5 months&#xD;
             after their last dose of study treatment.&#xD;
&#xD;
          -  All female participants must be of non-childbearing potential and must meet 1 of the&#xD;
             following criteria to participate in the study: a. Postmenopausal, b. History of&#xD;
             bilateral oophorectomy (performed at least 6 weeks prior to Screening), c. History of&#xD;
             hysterectomy (performed at least 6 weeks prior to Screening), or d. History of female&#xD;
             surgical sterilization (e.g., bilateral tubal ligation; performed at least 6 weeks&#xD;
             prior to Screening).&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  History of or ongoing clinically significant cardiac, endocrinologic, hematologic,&#xD;
             hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic,&#xD;
             psychiatric, renal, or other major disease, as determined by the Investigator.&#xD;
&#xD;
          -  Clinically significant abnormal laboratory test values, as determined by the&#xD;
             Investigator, at Screening or Check-in.&#xD;
&#xD;
          -  Use of any prescription medication, over-the-counter medication (e.g., aspirin and&#xD;
             nonsteroidal anti-inflammatory drugs [excluding acetaminophen]), or dietary and herbal&#xD;
             supplements (e.g., St. John's wort) within 28 days of Check-in and an unwillingness to&#xD;
             refrain from use through end of study (i.e., through the Day 91 visit), unless&#xD;
             specifically permitted elsewhere within the protocol.&#xD;
&#xD;
          -  Current enrollment in any other drug, biologic, device, or clinical study, or&#xD;
             treatment with an investigational drug or approved therapy for investigational use&#xD;
             within 30 days (6 months for biologics) or 5 half-lives, whichever is longer, prior to&#xD;
             Check-in.&#xD;
&#xD;
          -  History or physical examination that could be suggestive of a medical or mechanical&#xD;
             condition, disorder, or disease that could represent a relative contraindication to&#xD;
             lumbar puncture (LP), including but not limited to: (a) medication use that prolongs&#xD;
             coagulation times, including aspirin; (b) known disorders of the coagulation cascade,&#xD;
             platelet function, or platelet count; (c) low white blood cell counts; (d) chronic low&#xD;
             back pain; (e) prior lumbar spine surgery; (f) anatomical factors at or near the LP&#xD;
             site; (g) clinical signs of raised intracranial pressure (e.g., headache, papilledema,&#xD;
             or focal neurologic signs).&#xD;
&#xD;
          -  Contraindications to radiation exposure for research purposes.&#xD;
&#xD;
          -  Exposure to ionizing radiation within the last 12 months that would result in&#xD;
             approaching the exposure limits for healthy volunteers.&#xD;
&#xD;
        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Biogen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 3, 2018</study_first_submitted>
  <study_first_submitted_qc>December 3, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 5, 2018</study_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Technetium Tc 99m Mertiatide</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/NCT03764488
org study id: 233HV101
nct id: NCT03764488
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of the study is to evaluate the distribution in the central nervous
      system (CNS) of a microdose 99mTc-MAG3-BIIB067 co-administered with unlabeled BIIB067
      (Tofersen). The secondary objective of the study is to assess the safety and tolerability of
      unlabeled BIIB067 co-administered with a microdose of 99mTc-MAG3-BIIB067 to healthy
      participants.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: BIIB067 Concentrations Throughout the CNS
time frame: 1 to 24 hours post-dose on Day 1
description: BIIB067 concentrations throughout the CNS will be estimated by single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of 99mTc-MAG3-BIIB067.
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Up to Day 91
description: An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose: results in death, in the view of the Investigator, places the participant at immediate risk of death (a life-threatening event), however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event.
measure: Dose of Radiation Absorbed (Dosimetry) in Specific Regions of the CNS
time frame: 1 to 24 hours post-dose on Day 1
description: Dose of radiation absorbed (dosimetry) in specific regions of the CNS will be estimated by SPECT/CT imaging of 99mTc-MAG3-BIIB067.
arm group label: BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF
arm group type: Experimental
description: Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 15 milliliter (mL) artificial cerebrospinal fluid (aCSF).
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF
arm group type: Experimental
description: Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 15 mL aCSF.
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF
arm group type: Experimental
description: Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in 5 mL aCSF.
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF
arm group type: Experimental
description: Participants will receive intrathecal injection consisting of unlabeled BIIB067 and 99mTc-MAG3-BIIB067 in up to 20 mL aCSF.
intervention type: Drug
intervention name: Tofersen
description: Administered as specified in the treatment arm.
arm group label: BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF
other name: BIIB067
other name: QALSODY
intervention type: Drug
intervention name: 99mTc-MAG3-BIIB067
description: Administered as specified in the treatment arm.
arm group label: BIIB067 High Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 15 mL aCSF
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in 5 mL aCSF
arm group label: BIIB067 Low Dose + 99mTc-MAG3-BIIB067 in up to 20 mL aCSF
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Medical Director
role: Study Director
affiliation: Biogen
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Technetium Tc 99m Mertiatide