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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
8
Administered as specified in the treatment arm
Administered as specified in the treatment arm
University of California - Los Angeles
Los Angeles, California, United States
Number of Participants with Adverse Events (AEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Time frame: Day 1 to Day 267
Number of Participants with Serious Adverse Events (SAEs)
A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a-life threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.
Time frame: Screening to Day 267
Area Under the Concentration-Time Curve (AUC) of BIIB132
Time frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Area Under the Concentration Versus Time Curve, from Time of Dosing (Time = 0) to Infinity (AUCinf) of BIIB132
Time frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Area Under the Concentration Versus Time Curve, from Time of Dosing (Time = 0) to Time of the Last Measurable Effect (AUClast) of BIIB132
Time frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Maximum Observed Concentration (Cmax) of BIIB132
Time frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
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University of California San Francisco
San Francisco, California, United States
University of Florida, Center for Movement Disorders
Gainesville, Florida, United States
Movement Disorder Center Florida
Tampa, Florida, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Washington University
St Louis, Missouri, United States
Columbia Univeristy Medical Center
New York, New York, United States
Pennsylvania Neurological Institute
Philadelphia, Pennsylvania, United States
Houston Methodist Research Institute
Houston, Texas, United States
University of Washington
Seattle, Washington, United States
...and 10 more locations
Time to Reach Maximum Observed Concentration (Tmax) of BIIB132
Time frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Elimination Half-Life (t½) of BIIB132
Time frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85