A Pharmacokinetics and Safety Study of BIIB132 in Adults With Spinocerebellar Ataxia 3

A Phase 1, Blinded, Randomized, Placebo-controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Multiple Ascending Doses of BIIB132 Administered Intrathecally to Adults With Spinocerebellar Ataxia 3

The primary objective of this study is to evaluate the safety and tolerability of multiple ascending doses of BIIB132 administered via intrathecal (IT) injection to participants with spinocerebellar ataxia type 3 (SCA3). The secondary objective of this study is to characterize the multiple-dose pharmacokinetics (PK) of BIIB132 administered via IT injection to participants with SCA3.

BIIB132 is an investigational anti-sense oligonucleotide developed to target ataxin-3 (ATXN3) pre-messenger ribonucleic acid (pre-mRNA). Preclinical studies have shown that lowering of ATXN3 protein is associated with decreased progression of SCA3-like disease. This trial consists of a blinded 12 week study period with a 26 week follow up period to evaluate the safety and tolerability of intrathecal BIIB132 and to assess the effect on treatment response biomarkers in symptomatic SCA3 participants.

Key Inclusion Criteria:

• Diagnosis of SCA3 with CAG repeats ≥60 in ATXN3 gene.
• Symptomatic ataxia with a screening Scale for Assessment and Rating of Ataxia (SARA) score 3 to 15 (still ambulatory) and a minimum SARA gait subscore of 1.
• Able to ambulate 8 m independently without any assistive device.
• Treatment naïve or on a stable dose of symptomatic therapy for a minimum of 4 weeks prior to screening.

Key Exclusion Criteria:

• Unstable psychiatric illness or untreated major depression within 90 days before screening.
• History or screening magnetic resonance imaging (MRI) results show evidence of structural abnormalities that could contribute to the participant's clinical state other than findings typical of SCA3 or any finding that might pose a risk to the participant.
• MRI brain findings of prior cerebellar stroke or clinical stroke within 12 months before screening.
• History of brain surgery regardless of purpose.
• Any contraindications to undergoing brain MRI.
• History of, or ongoing, malignant disease, (with the exception of basal cell carcinomas and squamous cell carcinomas that have been completely excised and considered cured at least 12 months prior to screening). Participants with cancers in remission for longer than 5 years may be included.
• History of epilepsy or the occurrence of seizures within 3 years prior to screening.
• Evidence of untreated/unstable thyroid disease.
• Poorly controlled diabetes mellitus.
• History of alcohol or substance abuse within the past year prior to screening.
• Use of off-label drugs for ataxia within 4 weeks prior to screening.
• Prior enrollment in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 5 half-lives or 3 months, whichever is longer, prior to the screening visit.
• Any antiplatelet [except for aspirin up to 100 milligrams per day (mg/day)] or anticoagulant medication that cannot be safely interrupted for an lumbar puncture (LP) procedure.
• Any contraindications to LP procedures.
• Participants who are pregnant or currently breastfeeding and those intending to become pregnant during the study.
• Prior enrollment in any interventional clinical study in which an investigational treatment or approved therapy for investigational use is administered within 3 months prior to screening visit.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.