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.

Study Overview

• Status: Terminated
• Conditions: Spinocerebellar Ataxia Type 3
• Intervention / Treatment: Drug: BIIB132; Drug: BIIB132-Matching Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Baden Wuerttemberg
    • Tuebingen, Baden Wuerttemberg, Germany, 72076
      • UniversitaetsklinikumTübingen Neurologische Universitätsklinik
  • Nordrhein Westfalen
    • Bonn, Nordrhein Westfalen, Germany, 53127
      • Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
    • Essen, Nordrhein Westfalen, Germany, 45122
      • Universitaetsklinikum Essen Klinik für Neurologie
• Israel
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center
• Netherlands
  • Groningen, Netherlands, 9713 AG
    • Universitair Medisch Centrum Groningen (UMCG)
  • Nijmegen, Netherlands, 6525 GA
    • Radboudumc
• Portugal
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar de Lisboa Norte
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, WC1N 3BG
      • University College London Hospital (UCLH)
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LJ
      • Churchill Hospital
• United States
  • California
    • Los Angeles, California, United States, 90035
      • University of California - Los Angeles
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida, Center for Movement Disorders
    • Tampa, Florida, United States, 33612
      • Movement Disorder Center Florida
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Columbia Univeristy Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Neurological Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Research Institute
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: BIIB132 Dose 1 or Matching Placebo; Participants will be randomized to receive BIIB132 Dose 1 or matching placebo, intrathecally (IT), every 4 weeks (Q4W), up to Day 85.	Drug: BIIB132; Administered as specified in the treatment arm; Drug: BIIB132-Matching Placebo; Administered as specified in the treatment arm
Experimental: Cohort 2: BIIB132 Dose 2 or Matching Placebo; Participants will be randomized to receive BIIB132 Dose 2 or matching placebo, IT, Q4W, up to Day 85.	Drug: BIIB132; Administered as specified in the treatment arm; Drug: BIIB132-Matching Placebo; Administered as specified in the treatment arm
Experimental: Cohort 3: BIIB132 Dose 3 or Matching Placebo; Participants will be randomized to receive BIIB132 Dose 3 or matching placebo, IT, Q4W, up to Day 85.	Drug: BIIB132; Administered as specified in the treatment arm; Drug: BIIB132-Matching Placebo; Administered as specified in the treatment arm
Experimental: Cohort 4: BIIB132 Dose 4 or Matching Placebo; Participants will be randomized to receive BIIB132 Dose 4 or matching placebo, IT, Q4W, up to Day 85.	Drug: BIIB132; Administered as specified in the treatment arm; Drug: BIIB132-Matching Placebo; Administered as specified in the treatment arm
Experimental: Cohort 5: BIIB132 Dose 5 or 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.	Drug: BIIB132; Administered as specified in the treatment arm; Drug: BIIB132-Matching Placebo; Administered as specified in the treatment arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Screening to Day 267

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration-Time Curve (AUC) 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
Maximum Observed Concentration (Cmax) 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
Elimination Half-Life (t½) of BIIB132	Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Medical Director, Biogen

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2022
• Primary Completion (Actual): July 25, 2023
• Study Completion (Actual): July 25, 2023

Study Registration Dates

• First Submitted: December 7, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 16, 2021

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Cerebellar Diseases; Ataxia; Cerebellar Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease
• Other Study ID Numbers: 260SA101; 2021-002223-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No