In this study, researchers will learn more about the effects of BIIB147, in participants with amyotrophic lateral sclerosis, also known as ALS. ALS is a rare disease that damages the motor neurons in the brain and spinal cord that help control the movement of muscles in the body. It is a progressive disease, which means that it gets worse with time. Over time, this causes increasing problems with speaking, swallowing, moving the arms and legs, and breathing. In the case of ALS, this eventually leads to death from patients not being able to breathe.
This is a "first-in-human" study. This means that this study drug will be given to people for the very first time in this study. These studies are important because they help researchers learn about the safety of the study drug, how the body processes it, and what dose might be appropriate before testing it in larger groups.
The main goal of the study is to learn about the safety of BIIB147 in adult participants with ALS. The main question researchers want to answer is:
* How many participants have adverse events and serious adverse events during the study? Adverse events are health problems that may or may not be caused by the study drug. * Researchers will also learn more about:
* How much BIIB147 gets into the blood? * What is the highest amount of BIIB147 found in the blood? * How long does it take BIIB147 to reach its highest amount in the blood? * How much neurofilament light chain (NfL) protein is found in the blood? * How longer-term treatment with BIIB147 affects disease worsening and the participants' overall survival?
This study will be done as follows:
* Participants will join the study after signing an informed consent form, also known as an ICF. * Participants will be screened to check if they can join the study. The screening period will be up to 4 weeks. * Participants will be randomly assigned to get either the study drug BIIB147 or a placebo during the main treatment period. A placebo is something that looks like the study drug but does not contain any medicine. A placebo is also given the same as the study drug. * Neither the participants nor the researchers will know if participants are getting the study drug or the placebo. * BIIB147 or the placebo will be given through a lumbar puncture. This is done using a thin needle that is put into the lower part of the spine. * During the main treatment period, participants will have regular clinic visits and phone calls. At the visits, the study doctor will do tests to check the participants' overall health, including their brain and nerve function. The participants' breathing function, tongue strength, and muscle strength will also be checked. They will also measure the participants' height, weight, and vital signs and collect blood and urine samples. Participants will also complete questionnaires or answer questions about how they are feeling and about their daily lives. * After finishing treatment in the main part of the study, some participants who qualify may be able to join a "long-term extension" part of the study. This may last up to 6 years or more. During this part of the study, all participants will get BIIB147. * After the long-term extension is done, participants will join a follow-up safety period. If participants do not enter the long-term extension, they will go directly into the follow-up safety period once the treatment period is done. * Each participant will be in the study for up to 8 years or more.
Participants must have a diagnosis of ALS consistent with the Gold Coast criteria.
No pathogenic variants, likely pathogenic variants, or variants of uncertain significance in the superoxide dismutase 1 (SOD1) or fused in sarcoma (FUS) genes (confirmed by central genetic testing).
Greater than or equal to (≥) 50% of predicted value for slow vital capacity (SVC) as adjusted for sex, age, and height (from the sitting position).
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 end of study (EOS)/early termination (ET), unless the Investigator determines that it should be discontinued for medical reasons, in which case it may not be restarted during the study.
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.
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 NfL, in the opinion of the Investigator.
Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system during the study period.
Requires permanent ventilation (using > 22 hours per day [h/day] invasive or non-invasive ventilation)
Sequential
BIIB147
DrugAdministered intrathecally (IT)
Placebo
DrugAdministered IT
MAD, OLE, Integrated MAD and OLE Periods: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
MAD, OLE, Integrated MAD and OLE Periods: Serum Concentrations of Total Active BIIB147 Related Species
MAD, OLE, Integrated MAD and OLE Periods: Cerebrospinal Fluid (CSF) Concentrations of Total Active BIIB147 Related Species
MAD Period: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUCinf) of BIIB147
MAD Period: Area Under the Serum Concentration-Time Curve From Time Zero to Time of the Last Measurable Concentration (AUC0-last) of BIIB147
This trial is not recruiting at the moment. You can still explore other options:
