A Study of BIIB067 (Tofersen) Initiated in Clinically Presymptomatic Adults With a Confirmed Superoxide Dismutase 1 Mutation (ATLAS)
Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation
About this trial
This is an interventional treatment trial for Amyotrophic Lateral Sclerosis Associated With a SOD1 Gene Mutation
Eligibility Criteria
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 approved 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 manifest 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.
- Treatment with riluzole and/or edaravone. If the participant has been on riluzole and/or edaravone, the medication(s) must be discontinued for at least 5 half-lives prior to screening.
- Use of off-label treatments for ALS.
- 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.
- 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.
- 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.
Sites / Locations
- HonorHealth NeurologyRecruiting
- UC San DiegoRecruiting
- California Pacific Medical CenterRecruiting
- Holy Cross Hospital Phil Smith Neuroscience InstituteRecruiting
- University of MiamiRecruiting
- Emory UniversityRecruiting
- Northwestern UniversityRecruiting
- Johns Hopkins HospitalRecruiting
- Massachusetts General HospitalRecruiting
- Washington University School of MedicineRecruiting
- Columbia University Medical CenterRecruiting
- Austin Neuromuscular CenterRecruiting
- Macquarie UniversityRecruiting
- UZ LeuvenRecruiting
- Hospital Sao PauloRecruiting
- University of CalgaryRecruiting
- Sunnybrook Health Sciences CentreRecruiting
- Genge Partners Inc.Recruiting
- Hôpital Pitié-SalpêtrièreRecruiting
- Universitaetsklinikum UlmRecruiting
- Hannover Medical SchoolRecruiting
- Cresla "Rita Levi Montalcini" Department of NeuroscienceRecruiting
- Kagoshima University HospitalRecruiting
- University of Tokyo HospitalRecruiting
- Hanyang University Seoul HospitalRecruiting
- Centrum Medyczne Neuro ProtectRecruiting
- Hospital Universitari i Politecnic La FeRecruiting
- University Hospital of UmeaRecruiting
- SheffieldRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
No Intervention
Experimental
Experimental
Experimental
Part A: Natural History Run-in
Part B: Randomized, Double-Blind, Placebo-Controlled
Part C: Open-Label Extension
Part D: Open-Label Treatment
Participants enrolled in Part A will undergo blood draws approximately once every 28 days to assess neurofilament light chain (NfL) levels.
Participants from Part A who meet the protocol-defined NfL threshold and remain presymptomatic may be eligible to participate in Part B. During Part B, participants will receive tofersen 100 milligram (mg) or placebo via intrathecal (IT) injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.
Participants from Part B who develop clinically manifest ALS may be eligible to participate in Part C. During Part C, participants who received placebo in Part B will receive tofersen 100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years. Participants who received tofersen during Part B will receive tofersen 100 mg on Days 1, 29, and every 28 days thereafter for up to 2 years, with a dose of placebo on Day 15 to maintain the study blind.
Participants from Part A who develop clinically manifest ALS prior to randomization in Part B may be eligible to participate in Part D. During Part D, participants will receive tofersen100 mg via IT injection on Days 1, 15, 29, and every 28 days thereafter for up to 2 years.