ALSpire

This study is sponsored by Biogen.

Ataxin-2 (ATXN2) and ALS

Toxic clusters of a protein known as TAR DNA binding protein-43 (TDP-43) are found in about 97% of the brains of ALS patients, and are thought to be a central cause of the disease.

Research has shown that reducing another protein called Ataxin2 may reduce TDP-43 clusters and improve function.

Research has also shown that people carrying a certain mutation in Ataxin2 (called polyQ intermediate repeat) have a higher risk of developing ALS and may have faster disease progression.

The investigational drug (BIIB105) is designed to reduce Ataxin-2 in the brain and spinal cord, which may help reduce TDP-43 clusters and improve function in people with ALS with or without mutations in Ataxin2.

The aim of the study is to find out whether BIIB105 (the study drug) is safe and tolerable in people with ALS or ALS with a polyQ mutation.

Study activities

Participation is approximately 29 weeks and includes: *

• Screening Period (1 visit, up to 28 days before receiving study treatment)
  The study doctor and their staff will perform medical tests and assessments to determine if you are eligible to participate.
• Study Treatment Period (10 visits, up to 13 weeks)
  If you qualify and choose to participate, you will be randomly assigned (by chance) to receive either the investigational therapy or placebo. Your first dose of the investigational drug or placebo will occur during an overnight inpatient visit to the study center. You will receive four additional doses of the investigational drug or placebo at outpatient visits every 2 weeks. You will also have five clinic visits in between dosing visits, as well as telephone calls to check on your health.
• Follow-Up Period (2 visits, up to 12 weeks)
  You will return to the study location for some final tests and assessments, including lumbar punctures. You will also receive a phone call from a member of the study team to check on your health.

*A group of study participants (Group D2) will have a slightly longer study duration and receive the investigational drug or placebo at different intervals. Speak with a member of the study team for more information.

Among Other Eligibility Criteria, Participants Must:

• Be 18 years of age or older
• Meet the criteria for diagnosis of ALS
• Have a partner/caregiver who can attend the screening visit with you, remain consistent throughout the study, and provide information about you

Patients on a stable dose of riluzole and/or edaravone may be able to stay on their medication.

About the Investigational Drug (BIIB105)

• Antisense oligonucleotide (ASO) – a type of therapy that targets a specific gene and is believed to block it and may prevent it from making certain proteins
• designed to target the Ataxin2 gene
• The investigational drug is delivered intrathecally. Intrathecally means that the study drug is given to you by a procedure called a lumbar puncture.

More information

See below, to find out which ALS centres participate in this trial. For more information, please visit www.clinicaltrials.gov.