A Phase 3 Randomized, Placebo-Controlled Trial With a Longitudinal Natural History Run-In and Open-Label Extension to Evaluate BIIB067 Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation (ATLAS)

Study Purpose:

The primary objective of this study is to evaluate the efficacy of BIIB067 when initiated in presymptomatic adult carriers of a superoxide dismutase 1 (SOD1) mutation with elevated neurofilament (NF). The secondary objectives of this study are to evaluate the safety and tolerability of BIIB067 and to evaluate the effect of BIIB067 on pharmacodynamics (PD)/treatment response biomarkers.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase III

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

Clinicaltrials.gov ID (11 digit #):

NCT04856982

Neals Affiliated?

Yes

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:

Biogen

Participant Duration:

Estimated Enrollment:

150

Estimated Study Start Date:

05/17/2021

Estimated Study Completion Date:

08/07/2027

Posting Last Modified Date:

10/25/2021

Date Study Added to alsconsortium.org:

05/03/2021
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    N/A

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    Key Part A Inclusion Criteria:

    • Participants should have a protocol-defined rapidly progressive SOD1 mutation, confirmed by a central reader, or a SOD1 mutation that is adjudicated for inclusion by an external mutation adjudication committee.
    • Participants with plasma NfL level less than the protocol-defined threshold.
    • Participants who are clinically presymptomatic for ALS (i.e., must not have clinically manifested ALS).

    Key Part A Exclusion Criteria:

    • History or positive test result at screening for human immunodeficiency virus (HIV). The requirement for testing at Screening may be omitted if it is not permitted by local regulations.
    • Current hepatitis C infection (defined as positive Hepatitis C Virus (HCV) antibody and detectable HCV RNA). Participants with positive HCV antibody and undetectable HCV Ribonucleic Acid (RNA) are eligible to participate in the study (United States Centers for Disease Control and Prevention).
    • Current hepatitis B infection (defined as positive for hepatitis B surface antigen (HBsAg) and/or anti-Hepatitis B Core antibody (HBc)). Participants with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive anti-HBc, and positive anti-hepatitis B surface antibody (HBs) or vaccination (defined as negative HBsAg, negative anti-HBc, and positive anti- HBs) are eligible to participate in the study.
    • History of systemic hypersensitivity reaction to tofersen, the excipients contained in the formulation, and if appropriate, any diagnostic agents to be administered during the study.
    • History of confounding neuromuscular or neurological disorder that is expected to have a progressive (i.e., worsening) course during the study, and/or is expected to be associated with elevations in NF, in the opinion of the Investigator.
    • Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that if not managed optimally could place a participant at an increased risk for intraoperative or postoperative bleeding.
    • Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression ≤ 90 days of Screening, which in the opinion of the Investigator would interfere with the study procedures.
    • Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel) that cannot be safely continued or held for an LP procedure, if necessary, according to local or institutional guidelines and/or Investigator determination.
    • Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs), biological agent, or device within 1 month or 5 half-lives of study agent, whichever is longer. Specifically, no prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed.
    • Current enrollment or a plan to enroll in any interventional clinical study in which an investigational treatment, biological agent, device, or approved therapy for investigational use. Participation in a noninterventional study focused on ALS natural history may be allowed at the discretion of the Investigator.

    NOTE: Other protocol defined Inclusion/Exclusion criteria will apply.

  • Site Contact Information

    Research Site
    Scottsdale, Arizona 85251
    United States

    UC San Diego
    La Jolla, California 92037
    United States

    California Pacific Medical Center
    Ryan Razavi / .(JavaScript must be enabled to view this email address) / 415-600-0486
    San Francisco, California 94109
    United States

    Holy Cross Hospital Phil Smith Neuroscience Institute
    Donovan Mott / .(JavaScript must be enabled to view this email address) / 954-542-3442
    Fort Lauderdale, Florida 33308
    United States

    University of Miami
    Anne-Laure Grignon / .(JavaScript must be enabled to view this email address) / Miami, Florida 33136
    United States

    Emory University
    Meraida Polak / .(JavaScript must be enabled to view this email address) / 404-778-3807
    Atlanta, Georgia 30322
    United States

    Research Site
    Chicago, Illinois 60611
    United States

    Johns Hopkins Hospital
    Baltimore, Maryland 21287
    United States

    Massachusetts General Hospital
    Boston, Massachusetts 02114
    United States

    Washington University School of Medicine
    Dr Robert Bucelli / .(JavaScript must be enabled to view this email address) / 844-257-2273
    Saint Louis, Missouri 63110
    United States

    Research Site
    New York, New York 10032
    United States

    Austin Neuromuscular Center
    Yessar Hussain / .(JavaScript must be enabled to view this email address) / Stephanie Gonsoulin / .(JavaScript must be enabled to view this email address) / Austin, Texas 78756
    United States

    Research Site
    Sydney, New South Wales
    Australia

    Research Site
    Leuven,
    Belgium

    Research Site
    São Paulo,
    Brazil

    Research Site
    Calgary, Alberta
    Canada

    Research Site
    Toronto, Ontario
    Canada

    Research Site
    Montréal, Quebec
    Canada

    Research Site
    Paris,
    France

    Research Site
    Hannover,
    Germany

    Research Site
    Ulm,
    Germany

    Research Site
    Torino,
    Italy

    Research Site
    Kagoshima-shi, Kagoshima-Ken
    Japan

    University of Tokyo Hospital
    Bunkyo-ku, Tokyo-To
    Japan

    Research Site
    Warszawa,
    Poland

    Research Site
    Seoul,
    Republic of Korea

    Research Site
    Moscow,
    Russia

    Research Site
    Valencia,
    Spain

    Research Site
    Umeå,
    Sweden

    Research Site
    Sheffield, Staffordshire
    United Kingdom