A Study to Evaluate the Biological Effect of Tofersen in Adults With Amyotrophic Lateral Sclerosis Without Mutations in SOD1
The goal of this clinical trial is to evaluate whether tofersen is safe and effective in adults with non-SOD1 ALS. Tofersen is currently approved by the U.S. Food and Drug Administration to treat SOD1-ALS. The main questions it aims to answer are: * Does tofersen lower the levels of neurofilament light chain (NfL) in the blood and CSF of adult participants with non-SOD1 ALS? * Is tofersen safe and tolerable for adult participants with non-SOD1 ALS? * Does tofersen affect other measurements such as clinical outcomes and quality-of-life measures in participants with non-SOD1 ALS? Participants will : * Receive 100mg tofersen via lumbar puncture for 24 weeks. The doses are at the following time points: Weeks 0, 2, 4, 8, 12, 16, 20, and 24. * Complete 2 follow-up visits following the end of the dosing period at Weeks 28 and 32. * Complete a variety of questionnaires and outcome measurements such as strength and breathing testing.
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use PHI in accordance with national and local participant privacy regulations.
• Aged 18 years or older at the time of informed consent.
• Confirmed diagnosis of ALS.
• Time since onset of weakness due to ALS ≤ 24 months at the time of the screening visit.
• Prior confirmed genetic testing negative for SOD1 and FUS mutations. Participants with mutations in genes other than SOD1 and FUS may be enrolled at the discretion of the Site Investigator.
• SVC ≥ 50% of predicted value as adjusted for sex, age, and height (from the sitting position).
• 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.
• All participants must agree to practice effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment.
• If taking riluzole, participant must be on a stable dose for ≥ 30 days prior to Day 1 and expected to remain at that dose until the final study visit.
• If taking edaravone, participant must have initiated edaravone ≥ 60 days (2 treatment cycles) prior to Day 1 and expected to remain at that dose until the final study visit, unless the Investigator determines that edaravone should be discontinued for medical reasons, in which case it may not be restarted during the study.