A Pharmacokinetics and Safety Study of BIIB132 in Adults With Spinocerebellar Ataxia 3
- Conditions
- Spinocerebellar Ataxia Type 3
- Interventions
- Drug: BIIB132-Matching Placebo
- Registration Number
- NCT05160558
- Lead Sponsor
- Biogen
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 8
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cohort 4: BIIB132 Dose 4 or Matching Placebo BIIB132 Participants will be randomized to receive BIIB132 Dose 4 or matching placebo, IT, Q4W, up to Day 85. Cohort 3: BIIB132 Dose 3 or Matching Placebo BIIB132-Matching Placebo Participants will be randomized to receive BIIB132 Dose 3 or matching placebo, IT, Q4W, up to Day 85. Cohort 3: BIIB132 Dose 3 or Matching Placebo BIIB132 Participants will be randomized to receive BIIB132 Dose 3 or matching placebo, IT, Q4W, up to Day 85. Cohort 1: BIIB132 Dose 1 or Matching Placebo BIIB132 Participants will be randomized to receive BIIB132 Dose 1 or matching placebo, intrathecally (IT), every 4 weeks (Q4W), up to Day 85. Cohort 1: BIIB132 Dose 1 or Matching Placebo BIIB132-Matching Placebo Participants will be randomized to receive BIIB132 Dose 1 or matching placebo, intrathecally (IT), every 4 weeks (Q4W), up to Day 85. Cohort 2: BIIB132 Dose 2 or Matching Placebo BIIB132 Participants will be randomized to receive BIIB132 Dose 2 or matching placebo, IT, Q4W, up to Day 85. Cohort 2: BIIB132 Dose 2 or Matching Placebo BIIB132-Matching Placebo Participants will be randomized to receive BIIB132 Dose 2 or matching placebo, IT, Q4W, up to Day 85. Cohort 4: BIIB132 Dose 4 or Matching Placebo BIIB132-Matching Placebo Participants will be randomized to receive BIIB132 Dose 4 or matching placebo, IT, Q4W, up to Day 85. Cohort 5: BIIB132 Dose 5 or Matching Placebo BIIB132 Participants will be randomized to receive BIIB132 Dose 5 or matching placebo, IT, either Q4W or every 12 weeks (Q12W), up to Day 85 or every 8 weeks (Q8W) up to Day 57. Cohort 5: BIIB132 Dose 5 or Matching Placebo BIIB132-Matching Placebo Participants will be randomized to receive BIIB132 Dose 5 or matching placebo, IT, either Q4W or every 12 weeks (Q12W), up to Day 85 or every 8 weeks (Q8W) up to Day 57.
- Primary Outcome Measures
Name Time Method Number of Participants with Adverse Events (AEs) Day 1 to Day 267 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.
Number of Participants with Serious Adverse Events (SAEs) Screening to Day 267 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.
- Secondary Outcome Measures
Name Time Method Area Under the Concentration-Time Curve (AUC) of BIIB132 Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85 Maximum Observed Concentration (Cmax) of BIIB132 Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85 Elimination Half-Life (t½) of BIIB132 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 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 Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85 Time to Reach Maximum Observed Concentration (Tmax) of BIIB132 Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
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Trial Locations
- Locations (20)
University of California - Los Angeles
🇺🇸Los Angeles, California, United States
University of Florida, Center for Movement Disorders
🇺🇸Gainesville, Florida, United States
Centro Hospitalar do Porto
🇵🇹Porto, Portugal
Radboudumc
🇳🇱Nijmegen, Netherlands
Universitair Medisch Centrum Groningen (UMCG)
🇳🇱Groningen, Netherlands
Washington University
🇺🇸Saint Louis, Missouri, United States
Churchill Hospital
🇬🇧Oxford, Oxfordshire, United Kingdom
Pennsylvania Neurological Institute
🇺🇸Philadelphia, Pennsylvania, United States
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Movement Disorder Center Florida
🇺🇸Tampa, Florida, United States
UniversitaetsklinikumTübingen Neurologische Universitätsklinik
🇩🇪Tuebingen, Baden Wuerttemberg, Germany
Houston Methodist Research Institute
🇺🇸Houston, Texas, United States
Universitaetsklinikum Essen Klinik für Neurologie
🇩🇪Essen, Nordrhein Westfalen, Germany
University of California San Francisco
🇺🇸San Francisco, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Columbia Univeristy Medical Center
🇺🇸New York, New York, United States
Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
🇩🇪Bonn, Nordrhein Westfalen, Germany
Centro Hospitalar de Lisboa Norte
🇵🇹Lisboa, Portugal
University of Washington
🇺🇸Seattle, Washington, United States
University College London Hospital (UCLH)
🇬🇧London, Greater London, United Kingdom