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)
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 Chair(s)/Principal Investigator(s):
Clinicaltrials.gov ID (11 digit #):NCT04856982
Coordinating Center Contact Information
Full Study Summary:
Estimated Study Start Date:05/17/2021
Estimated Study Completion Date:08/07/2027
Posting Last Modified Date:05/13/2022
Date Study Added to alsconsortium.org:05/03/2021
Study website/pre-prescreening questionnaire: alsATLASstudy.com
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
Scottsdale, Arizona 85251
UC San Diego
La Jolla, California 92037
California Pacific Medical Center
San Francisco, California 94109
Holy Cross Hospital Phil Smith Neuroscience Institute
Fort Lauderdale, Florida 33308
University of Miami
Atlanta, Georgia 30322
Chicago, Illinois 60611
Johns Hopkins Hospital
Baltimore, Maryland 21287
Massachusetts General Hospital
Boston, Massachusetts 02114
Washington University School of Medicine
Saint Louis, Missouri 63110
Columbia University Medical Center
New York, New York 10032
Austin Neuromuscular Center
Sydney, New South Wales
University of Calgary
Montreal Neurological Hospital and Institute
Hannover Medical School
Kagoshima University Hospital
University of Tokyo Hospital
Centrum Medyczne Neuro Protect
Hanyang University Seoul Hospital
Republic of Korea
University Hospital of Umea