Clinical Trials

Inclusion Criteria: 

• Ability of the subject to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information in accordance with national and local subject privacy regulations; or, in the event of the subject’s physical incapacity to sign, to confirm that understanding and consent orally to a legally authorized representative (LAR) for the express purpose of having said informed consent and authorization signed on his/her behalf.
• Age ≥ 18 years old at the time of informed consent.
• All subjects of childbearing potential must agree to practice highly effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment. In addition, subjects should not donate sperm or eggs for the duration of the study and for at least 5 months after their last dose of study treatment.
• Must meet the possible, 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]) and have documentation of a clinical genetic test demonstrating the presence of a pathogenic mutation in C9ORF72.
• Slow vital capacity (SVC) ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position).
• Subjects taking concomitant riluzole at study entry must be on a stable dose for ≥ 30 days prior to the first dose of study treatment (Day 1). Subjects taking concomitant riluzole must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that riluzole should be discontinued for medical reasons, in which case it may not be restarted during the study.
• Subjects 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). Subjects taking concomitant edaravone must be willing to continue with the same dose regimen throughout the study, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study. Edaravone may not be administered on dosing days of this study.
• ALS Cognitive Behavioral Screen (ALS-CBS) score ≥ 11 for the cognitive portion; ≥ 33 for the behavioral portion.
• Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
• Screening values of platelet count and coagulation parameters including international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (APTT) should be within normal ranges. Coagulation tests may be done at a local laboratory in order to reduce participant burden. Platelet count and coagulation tests may be repeated once at the local laboratory if, in the opinion of the Investigator, values of the initial tests are out of range but not clinically significant. Participants with nonclinically significant and stable out-of-range values may be eligible to enroll in the study at the discretion of the Investigator, and after a consultation with the Sponsor.
• Has an informant/caregiver who, in the Investigator’s judgment, has frequent and sufficient contact with the subject as to be able to provide accurate information about the subject’s cognitive and functional abilities at Screening. An informant/caregiver should be available at Screening, and the participation of the informant/caregiver for the duration of the study is encouraged.

Exclusion Criteria: 

Medical History

• History of drug abuse or alcoholism ≤ 6 months of Screening that would limit participation in the study, as determined by the Investigator.
• Tracheostomy.
• History of a deep venous thrombosis or pulmonary embolism since the date of ALS diagnosis or ≤ 2 years of Screening, whichever duration is greater.
• Ongoing medical condition (e.g., wasting or cachexia, severe anemia) that would, in the opinion of the Investigator, interfere with the conduct or assessments of the study.
• Significant cognitive impairment 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.
• History of allergies to substances that will be used for the LP (e.g., anesthetics, if used per institutional practice).
• Presence of risk of bleeding that could place a subject at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand’s disease, liver disease).
• Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter.
• Presence of an implanted intravenous port/catheter.
• Clinically significant abnormalities in hematology or blood chemistry parameters, as determined by the Investigator, which would render the subject unsuitable for enrollment.
• Clinically significant, as determined by the Investigator, 12-lead electrocardiogram (ECG) abnormalities, including corrected QT interval using Fridericia’s correction method of >450 ms for males and >470 ms for females.
• Alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels ≥2 times the upper limit of normal. Patients with previously established Gilbert’s syndrome and elevated levels of bilirubin consistent with such syndrome are allowed in the study.

Infections

• History of or positive test result at Screening for human immunodeficiency virus. The requirement for testing at Screening may be omitted if it is not permitted by local regulations.
• History of, or positive test result at Screening for, hepatitis C virus antibody.
• Current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Subjects with immunity to hepatitis B from previous natural infection (defined as negative HBsAg, positive hepatitis B surface antibody immunoglobulin G, and positive HBcAb) or vaccination (defined as positive hepatitis B surface antibody) are eligible to participate in the study.
• Presence of an untreated or inadequately treated active infection requiring systemic antiviral or antimicrobial therapy at any time during the screening period.

Medications

• Treatment with another investigational drug (including investigational drugs for ALS through compassionate use programs) or biological agent within 1 month of Screening or 5 half-lives of study agent, whichever is longer.
• Treatment with antiplatelet or anticoagulant therapy ≤14 days before Screening (with the exception of aspirin ≤325 mg/day) or anticipated use during the study, including but not limited to clopidogrel, dipyridamole, warfarin, dabigatran, rivaroxaban, and apixaban.

Other

• Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
• Female subjects who are pregnant or currently breastfeeding.
• Concurrent enrollment in any other interventional study. Participation in a non-interventional study focused on ALS natural history may be allowed at the discretion of the Investigator and after consultation with the Sponsor.
• Inability to comply with study requirements.
• Other unspecified reasons that, in the opinion of the Investigator or Biogen, make the subject unsuitable for enrollment.