<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/NCT04494256</url>
  </required_header>
  <id_info>
    <org_study_id>275AS101</org_study_id>
    <secondary_id>2020-000207-36</secondary_id>
    <nct_id>NCT04494256</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Safety, Tolerability, and Effect on Disease Progression of BIIB105 in Participants With Amyotrophic Lateral Sclerosis (ALS) and Participants With the ALS Ataxin-2 (ATXN2) Genetic Mutation</brief_title>
  <acronym>ALSpire</acronym>
  <official_title>A Phase 1/2 Multiple-Ascending-Dose Study With a Long-Term Open-Label Extension to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Effect on Disease Progression of BIIB105 Administered Intrathecally to Adults With Amyotrophic Lateral Sclerosis With or Without Poly-CAG Expansion in the Ataxin-2 Gene</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 ALSpire Study is a clinical trial evaluating the investigational drug BIIB105 in adults&#xD;
      living with amyotrophic lateral sclerosis (ALS).&#xD;
&#xD;
      The ALSpire Study consists of two parts:&#xD;
&#xD;
        -  Part 1: 6-month placebo-controlled study. During Part 1, participants are randomly&#xD;
           assigned to receive either BIIB105 or placebo in a 3:1 or 2:1 ratio (depending on the&#xD;
           participant's assigned Cohort).&#xD;
&#xD;
        -  Part 2: 2-year long-term open-label extension. During Part 2, all participants receive&#xD;
           BIIB105.&#xD;
&#xD;
      The objectives of the study are to evaluate:&#xD;
&#xD;
        -  The safety and tolerability of BIIB105 in people with ALS&#xD;
&#xD;
        -  What the body does to BIIB105 (also called &quot;pharmacokinetics&quot;)&#xD;
&#xD;
        -  What BIIB105 does to the body (also called &quot;pharmacodynamics&quot;)&#xD;
&#xD;
        -  Whether BIIB105 can slow the worsening of clinical function&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      About BIIB105:&#xD;
&#xD;
      - BIIB105 is an investigational drug designed to reduce the levels of a protein called&#xD;
      ataxin-2. It is administered intrathecally (via a procedure called lumbar puncture).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 28, 2020</start_date>
  <completion_date type="Anticipated">July 15, 2026</completion_date>
  <primary_completion_date type="Anticipated">July 15, 2026</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>Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>Up to Day 260</time_frame>
    <description>An AE is any untoward medical occurrence in a participant 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, places the participant at immediate risk of 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>
  </primary_outcome>
  <primary_outcome>
    <measure>Part 2: Number of Participants with AEs and SAEs</measure>
    <time_frame>Up to Day 820</time_frame>
    <description>An AE is any untoward medical occurrence in a participant 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, places the participant at immediate risk of 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>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 1: Serum Concentrations of BIIB105</measure>
    <time_frame>Up to Day 176</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: CSF Concentrations of BIIB105</measure>
    <time_frame>Up to Day 259</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Area Under the Serum Concentration-Time Curve from Time Zero to Infinity (AUCinf)</measure>
    <time_frame>Up to Day 176</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast)</measure>
    <time_frame>Up to Day 176</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Maximum Observed Serum Concentration (Cmax)</measure>
    <time_frame>Up to Day 176</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax)</measure>
    <time_frame>Up to Day 176</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Elimination Half-Life (t1/2) in Serum</measure>
    <time_frame>Up to Day 176</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 1: Change From Baseline in Plasma Levels of Neurofilament Light Chain (NfL)</measure>
    <time_frame>Up to Day 259</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: CSF Trough PK Concentration of BIIB105</measure>
    <time_frame>Up to Day 819</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: Serum PK Concentration of BIIB105</measure>
    <time_frame>Up to Day 673</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: Change From Part 1 Baseline in Plasma Levels of NfL</measure>
    <time_frame>Up to Day 819</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: Change From Part 1 Baseline in Slow Vital Capacity (SVC)</measure>
    <time_frame>Up to Day 819</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: Change From Part 1 Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score</measure>
    <time_frame>Up to Day 819</time_frame>
    <description>The ALSFRS-R is used to predict survival. The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 to 4, for a total possible score of 48, with higher scores representing better function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: Change From Part 1 Baseline in Muscle Strength, as Measured by Handheld Dynamometry (HHD)</measure>
    <time_frame>Up to Day 819</time_frame>
    <description>Quantitative muscle strength will be evaluated using HHD, which tests isometric strength of multiple muscles using standard participant positioning. Approximately 8 muscle groups will be examined (per each side) in both upper and lower extremities.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: Time to Death or Permanent Ventilation</measure>
    <time_frame>Up to Day 820</time_frame>
    <description>Permanent ventilation is defined as ≥22 hours of mechanical ventilation [invasive or noninvasive] per day for ≥21 consecutive days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: Time to Death</measure>
    <time_frame>Up to Day 820</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Integrated Parts 1 and 2: Time to Death, Incorporating Post-Study Withdrawal or Study Completion Vital Status Data</measure>
    <time_frame>Up to Day 820</time_frame>
  </secondary_outcome>
  <number_of_arms>9</number_of_arms>
  <enrollment type="Anticipated">98</enrollment>
  <condition>Amyotrophic Lateral Sclerosis</condition>
  <arm_group>
    <arm_group_label>Part 1: Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with ALS will receive BIIB105 Dose 1, intrathecally (IT), as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with ALS will receive BIIB105 Dose 2, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort C1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with ALS will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort D1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with ALS will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort C2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with polyQ-ALS will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohort D2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with polyQ-ALS will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Cohorts A-D2: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants with ALS and polyQ-ALS for Cohorts A, B, C1 and C2 will receive matching placebo to BIIB105 as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days, and participants with ALS and polyQ-ALS for Cohorts D1 and D2 will receive matching placebo to BIIB105 as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Cohorts A-C2: Open-Label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who complete Cohorts A, B, C1, and C2 will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by twenty-five maintenance doses on twenty-five later days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Cohorts D1, D2: Open-Label</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who complete Cohorts D1 and D2 will have a blinded Loading Dose Period, during which those who received placebo in Part 1 will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, while those who received BIIB105 in Part 1 will receive 2 loading doses of BIIB105 Dose 4, IT, on Days 1 and one later day, and placebo on Day 15. After the blinded Loading Dose Period, participants will receive BIIB105 Dose 4 as twenty-five maintenance doses on twenty-five later days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIIB105</intervention_name>
    <description>Administered as specified in the treatment arm.</description>
    <arm_group_label>Part 1: Cohort A</arm_group_label>
    <arm_group_label>Part 1: Cohort B</arm_group_label>
    <arm_group_label>Part 1: Cohort C1</arm_group_label>
    <arm_group_label>Part 1: Cohort C2</arm_group_label>
    <arm_group_label>Part 1: Cohort D1</arm_group_label>
    <arm_group_label>Part 1: Cohort D2</arm_group_label>
    <arm_group_label>Part 2: Cohorts A-C2: Open-Label</arm_group_label>
    <arm_group_label>Part 2: Cohorts D1, D2: Open-Label</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered as specified in the treatment arm.</description>
    <arm_group_label>Part 1: Cohorts A-D2: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
        Part 1:&#xD;
&#xD;
          -  Ability of the participant to understand the purpose and risks of the study and&#xD;
             indicate informed consent, and the ability of the participant or the participant's&#xD;
             legally authorized representative, to provide signed and dated informed consent and&#xD;
             authorization to use protected health information in accordance with national and&#xD;
             local privacy regulations.&#xD;
&#xD;
          -  No known presence or family history of mutations in the superoxide dismutase 1 (SOD1)&#xD;
             or fused in sarcoma (FUS) genes.&#xD;
&#xD;
          -  Participants in Cohorts A, B, C1 and D1, must meet the laboratory-supported probable,&#xD;
             probable, or definite criteria for diagnosing ALS according to the World Federation of&#xD;
             Neurology El Escorial criteria (revised according to the Airlie House Conference 1998&#xD;
             [Brooks 2000]). Participants in Cohort C2 and D2, must meet any of the prior&#xD;
             conditions, but may also only meet clinically possible criteria for diagnosing ALS, or&#xD;
             exhibit weakness attributable to ALS in the presence of ataxin-2 protein (ATXN2)&#xD;
             intermediate repeats.&#xD;
&#xD;
          -  In participants in Cohorts C2 and D2, confirmed intermediate&#xD;
             cytosine-adenine-guanine/cytosine-adenine-adenine (CAG/CAA) repeat expansion in the&#xD;
             ataxin-2 (ATXN2) gene as defined by at least 1 allele carrying 30 to 33 CAG/CAA&#xD;
             repeats.&#xD;
&#xD;
          -  Slow vital capacity (SVC) criteria:&#xD;
&#xD;
          -  In participants in Cohorts A, B, C1, and D1, SVC ≥60% of predicted value as adjusted&#xD;
             for sex, age, and height (from the sitting position).&#xD;
&#xD;
          -  In participants in Cohort C2 and D2, SVC ≥50% of predicted value as adjusted for sex,&#xD;
             age, and height (from the sitting position).&#xD;
&#xD;
          -  If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1&#xD;
             and expected to remain at that dose until the final study visit, unless the&#xD;
             Investigator determines that it should be discontinued for medical reasons, in which&#xD;
             case it may not be restarted during the study.&#xD;
&#xD;
          -  Participants taking concomitant edaravone at study entry must be on a stable dose for&#xD;
             ≥60 days prior to the first dose of study treatment (Day 1). Participants taking&#xD;
             concomitant edaravone must be willing to continue with the same dose regimen&#xD;
             throughout the study, unless the Investigator determines that edaravone should be&#xD;
             discontinued for medical reasons, in which case it may not be restarted during the&#xD;
             study. Edaravone may not be administered on dosing days of this study.&#xD;
&#xD;
          -  Screening values of coagulation parameters including platelet count, international&#xD;
             normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin&#xD;
             time (aPTT) should be within normal ranges.&#xD;
&#xD;
          -  Has an informant/caregiver who, in the Investigator's judgment, has frequent and&#xD;
             sufficient contact with the participant as to be able to provide accurate information&#xD;
             about the participant's cognitive and functional abilities at screening.&#xD;
&#xD;
        Part 2:&#xD;
&#xD;
          -  Ability of the participant to understand the purpose and risks of the study and&#xD;
             indicate informed consent, and the ability of the participant or the participant's&#xD;
             legally authorized representative to provide signed and dated informed consent and&#xD;
             authorization to use protected health information in accordance with national and&#xD;
             local privacy regulations&#xD;
&#xD;
          -  Participants must have completed Study NCT04494256 Part 1 through Week 25 (Day 175&#xD;
             Visit for Cohorts A, B, C1, C2; Day 176 Visit for Cohorts D1, D2). This inclusion&#xD;
             criterion does not apply to a participant if Part 1 was terminated by the Sponsor&#xD;
             before the participant reached Week 25.&#xD;
&#xD;
          -  Participants from Cohorts A, B, C1, and C2 must have a washout of ≥16 weeks between&#xD;
             the last dose of study treatment received in Study NCT04494256 Part 1 and the first&#xD;
             dose of BIIB105 received in Study NCT04494256 Part 2. Participants from Cohorts D1 and&#xD;
             D2 do not require a washout period.&#xD;
&#xD;
          -  If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1&#xD;
             and expected to remain at that dose until the final study visit, unless the&#xD;
             Investigator determines that it should be discontinued for medical reasons, in which&#xD;
             case it may not be restarted during the study.&#xD;
&#xD;
          -  Participants taking concomitant edaravone at study entry must be on a stable dose for&#xD;
             ≥60 days prior to the first dose of study treatment (Day 1). Participants taking&#xD;
             concomitant edaravone must be willing to continue with the same dose regimen&#xD;
             throughout the study, unless the Investigator determines that edaravone should be&#xD;
             discontinued for medical reasons, in which case it may not be restarted during the&#xD;
             study. Edaravone may not be administered on dosing days of this study.&#xD;
&#xD;
          -  Screening values of coagulation parameters including platelet count, INR, PT, and aPTT&#xD;
             should be within normal ranges.&#xD;
&#xD;
        Key Exclusion Criteria&#xD;
&#xD;
        Part 1:&#xD;
&#xD;
          -  History or positive test result at Screening for human immunodeficiency virus (HIV).&#xD;
&#xD;
          -  Current hepatitis C infection.&#xD;
&#xD;
          -  Current hepatitis B infection.&#xD;
&#xD;
          -  History of alcohol or substance abuse ≤6 months of Screening that would limit&#xD;
             participation in the study, as determined by the Investigator.&#xD;
&#xD;
          -  Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing&#xD;
             system during the study period.&#xD;
&#xD;
          -  Presence of tracheostomy.&#xD;
&#xD;
          -  In participants from Cohorts A, B, C1, and D1, history of myocardial infarction, as&#xD;
             determined by the Investigator.&#xD;
&#xD;
          -  In participants from Cohorts A, B, C1, and D1, poorly controlled type 1 or 2 diabetes&#xD;
             mellitus defined as hemoglobin A1c (HbA1c) ≥8% during Screening.&#xD;
&#xD;
          -  In participants in Cohorts A, B, and C1, prescreening ALSFRS-R slope &gt;-0.4&#xD;
             points/month, where prescreening ALSFRS-R slope is defined as: (ALSFRS-R score at&#xD;
             Screening - 48) / (months from date of symptom onset to date of Screening). This&#xD;
             criterion is not applicable for Cohorts C2, D1, and D2.&#xD;
&#xD;
          -  Treatment with another investigational drug (including investigational drugs for ALS&#xD;
             through compassionate use programs) or biological agent within 1 month or 5 half-lives&#xD;
             of study agent, whichever is longer, before Screening.&#xD;
&#xD;
          -  Treatment with an approved disease-modifying therapy for ALS other than riluzole or&#xD;
             edaravone within 1 month or 5 half-lives of therapy, whichever is longer, before&#xD;
             screening.&#xD;
&#xD;
          -  Treatment with an antiplatelet or anticoagulant therapy that cannot safely be&#xD;
             interrupted for lumbar puncture (LP) according to local standard of care and/or&#xD;
             institutional guidelines, in the opinion of the Investigator or Prescriber.&#xD;
&#xD;
          -  Female participants who are pregnant or currently breastfeeding and those intending to&#xD;
             become pregnant during the study.&#xD;
&#xD;
        Part 2:&#xD;
&#xD;
          -  History or positive test result at Screening for HIV. If participants from Cohorts D1&#xD;
             and D2 who would seamlessly roll from Part 1 into Part 2 test positive for HIV during&#xD;
             screening for Part 2 but are clinically asymptomatic, they may enroll in Part 2 at the&#xD;
             discretion of the Investigator.&#xD;
&#xD;
          -  Current hepatitis C infection. If participants from Cohorts D1 and D2 who would&#xD;
             seamlessly roll from Part 1 into Part 2 test positive for hepatitis C during screening&#xD;
             for Part 2 but are clinically asymptomatic, they may enroll in Part 2 at the&#xD;
             discretion of the Investigator.&#xD;
&#xD;
          -  Current hepatitis B infection. If participants from Cohorts D1 and D2 who would&#xD;
             seamlessly roll from Part 1 into Part 2 test positive for hepatitis B during screening&#xD;
             for Part 2 but are clinically asymptomatic, they may enroll in Part 2 at the&#xD;
             discretion of the Investigator.&#xD;
&#xD;
          -  History of alcohol or substance abuse ≤ 6 months of Screening that would limit&#xD;
             participation in the study, as determined by the Investigator.&#xD;
&#xD;
          -  Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing&#xD;
             system during the study period.&#xD;
&#xD;
          -  In participants from Cohorts A, B, C1, and D1, history of myocardial infarction, as&#xD;
             determined by the Investigator.&#xD;
&#xD;
          -  In participants from Cohorts A, B, C1, and D1, poorly controlled type 1 or 2 diabetes&#xD;
             mellitus defined as HbA1c ≥8% during Screening.&#xD;
&#xD;
          -  Treatment with another investigational drug (including investigational drugs for ALS&#xD;
             through compassionate use programs; excluding BIIB105) or biological agent within 1&#xD;
             month or 5 half-lives of study agent, whichever is longer, before Screening.&#xD;
&#xD;
          -  Treatment with an antiplatelet or anticoagulant therapy that cannot safely be&#xD;
             interrupted for LP according to local standard of care and/or institutional&#xD;
             guidelines, in the opinion of the Investigator or Prescriber.&#xD;
&#xD;
          -  Female participants who are pregnant or currently breastfeeding and those intending to&#xD;
             become pregnant during the study.&#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>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Biogen</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>US Biogen Clinical Trial Center</last_name>
    <phone>866-633-4636</phone>
    <email>clinicaltrials@biogen.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Global Biogen Clinical Trial Center</last_name>
    <email>clinicaltrials@biogen.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Barrow Neurological Institute</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85013</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>602-406-6262</phone>
    </contact>
    <investigator>
      <last_name>Shafeeq S. Ladha</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UCSD</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rosemarie Previte</last_name>
      <email>rprevite@health.ucsd.edu</email>
    </contact>
    <investigator>
      <last_name>John Ravits</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Stanford Neuromuscular Research Center</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>650-725-4341</phone>
      <email>NeuromuscularResearch@stanford.edu</email>
    </contact>
    <investigator>
      <last_name>John Day</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital - Neuroscience Center -Anschutz Medical Campus</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Recruitment Coordinator</last_name>
      <phone>303-724-4644</phone>
      <email>NeuroResearch@cuanschutz.edu</email>
    </contact>
    <contact_backup>
      <last_name>Principal Investigator</last_name>
      <phone>7208488530</phone>
    </contact_backup>
    <investigator>
      <last_name>Laura A Foster</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Georgetown University</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007-2113</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>646-797-8917</phone>
    </contact>
    <investigator>
      <last_name>Nicholas Streicher</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Florida</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jany Paulett</last_name>
      <phone>904-953-3730</phone>
      <email>Paulett.jany@mayo.edu</email>
    </contact>
    <investigator>
      <last_name>Bjorn Oskarsson</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Orlando Health</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>321-841-2800</phone>
    </contact>
    <investigator>
      <last_name>Vahid Tohidi</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Emory Clinic</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Glass</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>ALS Clinic - Department of Neurology, Neuromuscular Division, Johns Hopkins University, School of Medicine</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21218</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristen Riley, PhD</last_name>
      <email>kriley15@jhmi.edu</email>
    </contact>
    <investigator>
      <last_name>Jeffrey Rothstein</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Erica Scirocco</last_name>
      <phone>617-726-1363</phone>
      <email>escirocco@mgh.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Suma Babu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Washington University, School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>1-844-ALS-CARE</phone>
      <email>als@wustl.edu</email>
    </contact>
    <investigator>
      <last_name>Robert Bucelli</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stephanie Hansen</last_name>
      <phone>215-662-4067</phone>
      <email>stephanie.hansen@pennmedicine.upenn.edu</email>
    </contact>
    <investigator>
      <last_name>Lauren Elman</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Houston Methodist Neurological Institute</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>713-363-7310</phone>
    </contact>
    <investigator>
      <last_name>Bing Liao</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84132</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael Papadakis</last_name>
      <email>m.papadakis@utah.edu</email>
    </contact>
    <investigator>
      <last_name>Summer Gibson</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Montreal Neurological Institute-Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3A 2B4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dipannita Purkayastha</last_name>
      <phone>514-398-6183</phone>
      <email>dipannita.purkayastha@mcgill.ca</email>
    </contact>
    <investigator>
      <last_name>Angela Genge</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>A.O.U. Città della salute e della scienza di Torino</name>
      <address>
        <city>Torino</city>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <email>cresla.torino@gmail.com</email>
    </contact>
    <investigator>
      <last_name>Adriano Chiò</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UMC Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>0031(0)887553204</phone>
      <email>trialALS@UMCutrecht.nl</email>
    </contact>
    <investigator>
      <last_name>L.H. van den Berg</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.biogentriallink.com/en-us/home.html</url>
    <description>Biogen Trial Link</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>July 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>August 29, 2023</last_update_submitted>
  <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
    <mesh_term>Disease Progression</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/</ipd_description>
    <ipd_url>https://vivli.org/</ipd_url>
  </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/NCT04494256
org study id: 275AS101
secondary id: 2020-000207-36
nct id: NCT04494256
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The ALSpire Study is a clinical trial evaluating the investigational drug BIIB105 in adults
      living with amyotrophic lateral sclerosis (ALS).

      The ALSpire Study consists of two parts:

        -  Part 1: 6-month placebo-controlled study. During Part 1, participants are randomly
           assigned to receive either BIIB105 or placebo in a 3:1 or 2:1 ratio (depending on the
           participant's assigned Cohort).

        -  Part 2: 2-year long-term open-label extension. During Part 2, all participants receive
           BIIB105.

      The objectives of the study are to evaluate:

        -  The safety and tolerability of BIIB105 in people with ALS

        -  What the body does to BIIB105 (also called "pharmacokinetics")

        -  What BIIB105 does to the body (also called "pharmacodynamics")

        -  Whether BIIB105 can slow the worsening of clinical function
About BIIB105:

      - BIIB105 is an investigational drug designed to reduce the levels of a protein called
      ataxin-2. It is administered intrathecally (via a procedure called lumbar puncture).
allocation: Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Part 1: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
time frame: Up to Day 260
description: An AE is any untoward medical occurrence in a participant 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, places the participant at immediate risk of 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: Part 2: Number of Participants with AEs and SAEs
time frame: Up to Day 820
description: An AE is any untoward medical occurrence in a participant 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, places the participant at immediate risk of 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: Part 1: Serum Concentrations of BIIB105
time frame: Up to Day 176
measure: Part 1: CSF Concentrations of BIIB105
time frame: Up to Day 259
measure: Part 1: Area Under the Serum Concentration-Time Curve from Time Zero to Infinity (AUCinf)
time frame: Up to Day 176
measure: Part 1: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUClast)
time frame: Up to Day 176
measure: Part 1: Maximum Observed Serum Concentration (Cmax)
time frame: Up to Day 176
measure: Part 1: Time to Reach Maximum Observed Serum Concentration (Tmax)
time frame: Up to Day 176
measure: Part 1: Elimination Half-Life (t1/2) in Serum
time frame: Up to Day 176
measure: Part 1: Change From Baseline in Plasma Levels of Neurofilament Light Chain (NfL)
time frame: Up to Day 259
measure: Integrated Parts 1 and 2: CSF Trough PK Concentration of BIIB105
time frame: Up to Day 819
measure: Integrated Parts 1 and 2: Serum PK Concentration of BIIB105
time frame: Up to Day 673
measure: Integrated Parts 1 and 2: Change From Part 1 Baseline in Plasma Levels of NfL
time frame: Up to Day 819
measure: Integrated Parts 1 and 2: Change From Part 1 Baseline in Slow Vital Capacity (SVC)
time frame: Up to Day 819
measure: Integrated Parts 1 and 2: Change From Part 1 Baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score
time frame: Up to Day 819
description: The ALSFRS-R is used to predict survival. The ALSFRS-R measures 4 functional domains, including respiratory, bulbar function, gross motor skills, and fine motor skills. There are 12 questions, each scored from 0 to 4, for a total possible score of 48, with higher scores representing better function.
measure: Integrated Parts 1 and 2: Change From Part 1 Baseline in Muscle Strength, as Measured by Handheld Dynamometry (HHD)
time frame: Up to Day 819
description: Quantitative muscle strength will be evaluated using HHD, which tests isometric strength of multiple muscles using standard participant positioning. Approximately 8 muscle groups will be examined (per each side) in both upper and lower extremities.
measure: Integrated Parts 1 and 2: Time to Death or Permanent Ventilation
time frame: Up to Day 820
description: Permanent ventilation is defined as ≥22 hours of mechanical ventilation [invasive or noninvasive] per day for ≥21 consecutive days.
measure: Integrated Parts 1 and 2: Time to Death
time frame: Up to Day 820
measure: Integrated Parts 1 and 2: Time to Death, Incorporating Post-Study Withdrawal or Study Completion Vital Status Data
time frame: Up to Day 820
arm group label: Part 1: Cohort A
arm group type: Experimental
description: Participants with ALS will receive BIIB105 Dose 1, intrathecally (IT), as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
arm group label: Part 1: Cohort B
arm group type: Experimental
description: Participants with ALS will receive BIIB105 Dose 2, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
arm group label: Part 1: Cohort C1
arm group type: Experimental
description: Participants with ALS will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
arm group label: Part 1: Cohort D1
arm group type: Experimental
description: Participants with ALS will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.
arm group label: Part 1: Cohort C2
arm group type: Experimental
description: Participants with polyQ-ALS will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days.
arm group label: Part 1: Cohort D2
arm group type: Experimental
description: Participants with polyQ-ALS will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.
arm group label: Part 1: Cohorts A-D2: Placebo
arm group type: Placebo Comparator
description: Participants with ALS and polyQ-ALS for Cohorts A, B, C1 and C2 will receive matching placebo to BIIB105 as 3 loading doses on Day 1 and two later days, followed by two maintenance doses on two later days, and participants with ALS and polyQ-ALS for Cohorts D1 and D2 will receive matching placebo to BIIB105 as 3 loading doses on Day 1 and two later days, followed by five maintenance doses on five later days.
arm group label: Part 2: Cohorts A-C2: Open-Label
arm group type: Experimental
description: Participants who complete Cohorts A, B, C1, and C2 will receive BIIB105 Dose 3, IT, as 3 loading doses on Day 1 and two later days, followed by twenty-five maintenance doses on twenty-five later days.
arm group label: Part 2: Cohorts D1, D2: Open-Label
arm group type: Experimental
description: Participants who complete Cohorts D1 and D2 will have a blinded Loading Dose Period, during which those who received placebo in Part 1 will receive BIIB105 Dose 4, IT, as 3 loading doses on Day 1 and two later days, while those who received BIIB105 in Part 1 will receive 2 loading doses of BIIB105 Dose 4, IT, on Days 1 and one later day, and placebo on Day 15. After the blinded Loading Dose Period, participants will receive BIIB105 Dose 4 as twenty-five maintenance doses on twenty-five later days.
intervention type: Drug
intervention name: BIIB105
description: Administered as specified in the treatment arm.
arm group label: Part 1: Cohort A
arm group label: Part 1: Cohort B
arm group label: Part 1: Cohort C1
arm group label: Part 1: Cohort C2
arm group label: Part 1: Cohort D1
arm group label: Part 1: Cohort D2
arm group label: Part 2: Cohorts A-C2: Open-Label
arm group label: Part 2: Cohorts D1, D2: Open-Label
intervention type: Drug
intervention name: Placebo
description: Administered as specified in the treatment arm.
arm group label: Part 1: Cohorts A-D2: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Biogen
last name: US Biogen Clinical Trial Center
phone: 866-633-4636
email: clinicaltrials@biogen.com
last name: Global Biogen Clinical Trial Center
email: clinicaltrials@biogen.com
facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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status: Recruiting
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country: Canada
country: Italy
country: Netherlands
country: United States
url: https://www.biogentriallink.com/en-us/home.html
description: Biogen Trial Link
responsible party type: Sponsor
mesh term: Motor Neuron Disease
mesh term: Amyotrophic Lateral Sclerosis
mesh term: Sclerosis
mesh term: Disease Progression
sharing ipd: Yes
ipd description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
ipd url: https://vivli.org/