A Phase 1 Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB105 Administered Intrathecally to Adults With Amyotrophic Lateral Sclerosis With or Without Poly-CAG Expansion in the Ataxin-2 Gene

Study Purpose:

The primary objective is to evaluate the safety and tolerability of BIIB105 in participants with amyotrophic lateral sclerosis (ALS) or poly-CAG expansion (polyQ)-ALS. The secondary objective is to assess the pharmacokinetic (PK) profile of BIIB105 in serum of participants with ALS or poly-CAG expansion (polyQ)-ALS.


Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:



Phase I

Study Chair(s)/Principal Investigator(s):

Clinicaltrials.gov ID (11 digit #):


Neals Affiliated?


Coordinating Center Contact Information

US Biogen Clinical Trial Center / .(JavaScript must be enabled to view this email address) / 866-633-4636
.(JavaScript must be enabled to view this email address) United States

Full Study Summary:

Study Sponsor:


Participant Duration:

Estimated Enrollment:


Estimated Study Start Date:


Estimated Study Completion Date:


Posting Last Modified Date:


Date Study Added to alsconsortium.org:

  • Eligibility Criteria


    Female, Male

    Minimum Age:


    Maximum Age:


    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?


    Key Inclusion Criteria:

    Ability of the participant and/or his/her legally authorized representative (e.g., parent, spouse, or legal guardian), as appropriate and applicable, to understand the purpose and risks of the study, to provide informed consent, and to authorize the use of confidential health information in accordance with national and local privacy regulations.

    All women of childbearing potential and all men must ensure that highly effective contraception is used during the study and for at least 6 months for female participants and 8 months for male participants after their last dose of study treatment.

    No known presence or family history of mutations in the superoxide dismutase 1 (SOD1) or fused in sarcoma (FUS) genes.

    Participants in Cohorts A, B, C1 and D1, must meet the laboratory-supported probable, probable, or definite criteria for diagnosing ALS according to the World Federation of Neurology El Escorial criteria (revised according to the Airlie House Conference 1998 [Brooks 2000]). Participants in Cohort C2 and D2, must meet any of the prior conditions, but may also only meet clinically possible criteria for diagnosing ALS, or exhibit weakness attributable to ALS in the presence of ataxin-2 protein (ATXN2) intermediate repeats.

    In participants in Cohorts C2 and D2, confirmed intermediate cytosine-adenine-guanine/cytosine- adenine-adenine (CAG/CAA) repeat expansion in the ataxin-2 gene or RNA (ATXN2) gene as defined by at least 1 allele carrying 30 to 33 CAG/CAA repeats.

    Slow vital capacity (SVC) criteria:

    • In participants in Cohorts A, B, C1, and D1, SVC 60% of predicted value as adjusted for sex, age, and height (from the sitting position).
    • In participants in Cohorts C2 and D2, SVC ≥50% of predicted value as adjusted for sex, age, and height (from the sitting position).

    If taking riluzole, participant must be on a stable dose for

    • 30 days prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study.

    Participants taking concomitant edaravone at study entry must be on a stable dose for ≥60 days prior to the first dose of study treatment (Day 1).
    Screening values of coagulation parameters including platelet count, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) should be within normal ranges.
    Has an informant/caregiver who, in the Investigator's judgment, has frequent and sufficient contact with the participant as to be able to provide accurate information about the participant's cognitive and functional abilities at screening.

    Key Exclusion Criteria

    History or positive test result at Screening for HIV.
    Current hepatitis C infection.
    Current hepatitis B infection.
    History of alcohol or substance abuse ≤6 months of Screening that would limit participation in the study, as determined by the Investigator.
    Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
    Presence of tracheostomy.
    In participants from Cohorts A, B, C1, and D1, history of myocardial infarction, as determined by the Investigator.
    In participants from Cohorts A, B, C1, and D1, poorly controlled type 1 or 2 diabetes mellitus defined as HbA1c

    • 8% during Screening.

    Prescreening Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) slope > -0.4 points/month, where prescreening ALSFRS-R slope is defined as: (48 - ALSFRS-R score at Screening) / (months from date of symptom onset to date of Screening) in participants from Cohorts A, B, C1, and D1.
    Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs) or biological agent within 1 month or 5 half-lives of study agent, whichever is longer, before Screening.
    Treatment with an antiplatelet or anticoagulant therapy that cannot safely be interrupted for lumbar puncture (LP) according to local standard of care and/or institutional guidelines, in the opinion of the Investigator or Prescriber.
    Female participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.

  • Site Contact Information

    Research Site
    La Jolla, California 92093
    United States

    Research Site
    Stanford, California 94305
    United States

    Research Site
    Jacksonville, Florida 32224
    United States

    Research Site
    Atlanta, Georgia 30322
    United States

    Research Site
    Baltimore, Maryland 21218
    United States

    Research Site
    Boston, Massachusetts 02114
    United States

    Research Site
    Saint Louis, Missouri 63110
    United States

    Research Site
    Philadelphia, Pennsylvania 19104
    United States

    Research Site
    Salt Lake City, Utah 84132
    United States

    Research Site
    Montreal, Quebec

    Research Site

    Research Site