An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)

Key Inclusion Criteria: Part A and B

• Weakness attributable to ALS and documented SOD1 mutation at Screening Visit 2.
• A forced vital capacity (FVC) ≥50% of predicted value as adjusted for sex, age, andheight (from the sitting position). Participants with stable FVC <50% but ≥45%, whoseFVC has not declined by more than 5% in the last 6 months may be considered forinclusion, at the discretion of the Investigator.
• If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1and expected to remain at that dose until the final study visit.
• Medically able to undergo the study procedures, and to adhere to the visit schedule atthe time of study entry, as determined by the Investigator.

Key Exclusion Criteria: Part A and B

• History of or positive test result for human immunodeficiency virus.
• 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]). Participants with immunity tohepatitis B from previous natural infection (defined as negative HBsAg, positivehepatitis B surface antibody immunoglobulin G, and positive HBcAb) or vaccination (defined as positive anti-HBs) are eligible to participate in the study.
• Treatment with another investigational drug, biological agent, or device within 1month or 5 half-lives of study agent, whichever is longer. Specifically, no priortreatment with small interfering ribonucleic acid, stem cell therapy, or gene therapyis allowed.
• Current enrollment in any other interventional study.
• Current or recent (within 1 month) use, or anticipated need, in the opinion of theInvestigator, of copper (II) (diacetyl-bis (N4-methylthiosemicarbazone)) orpyrimethamine.
• Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacingsystem (DPS) during the study period. Key Inclusion Criteria: Part C
• Weakness attributable to ALS and confirmed SOD1 mutation at Screening Visit.
• If taking riluzole, participant must be on a stable dose for ≥30 days prior to Day 1and expected to remain at that dose until the final study visit.
• If taking edaravone, participant must have initiated edaravone ≥60 days (2 treatmentcycles) prior to Day 1 and expected to remain at that dose until the final studyvisit, unless the Investigator determines that edaravone should be discontinued formedical reasons, in which case it may not be restarted during the study. Edaravone maynot be administered on dosing days of this study.
• Medically able to undergo the study procedures and to adhere to the visit schedule atthe time of study entry, as determined by the Investigator. Key Exclusion Criteria: Part C
• History of or positive test result for human immunodeficiency virus.
• Current hepatitis C infection (defined as positive hepatitis C virus [HCV] antibodyand detectable HCV ribonucleic acid [RNA]). Participants with positive HCV antibodyand undetectable HCV RNA are eligible to participate in the study (United StatesCenters for Disease Control and Prevention).
• Current hepatitis B infection (defined as positive for HBsAg and/or anti-HBc).participants with immunity to hepatitis B from previous natural infection (defined asnegative HBsAg, positive anti-HBc, and positive anti-HBs) or vaccination (defined asnegative HBsAg, negative anti-HBc, and positive anti-HBs) are eligible to participatein the study.
• Treatment with another investigational drug (including investigational drugs for ALSthrough compassionate use programs), biological agent, or device within 1 month or 5half-lives of study agent, whichever is longer. Specifically, no prior treatment withsmall interfering RNA, stem cell therapy, or gene therapy is allowed.
• Current enrollment in any other interventional study.
• Current or recent (within 1 month) use, or anticipated need, in the opinion of theInvestigator, of copper (II) (diacetyl-bis(N4-methylthiosemicarbazone)) orpyrimethamine.
• Current or anticipated need, in the opinion of the Investigator, of a DPS during thestudy period. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.