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

NCT ID: NCT05160558

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-02
• Study Completion Date: 2023-07-25

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.

Conditions

Spinocerebellar Ataxia Type 3

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

BIIB132

Intervention Type: DRUG

Administered as specified in the treatment arm

BIIB132-Matching Placebo

Intervention Type: DRUG

Administered as specified in the treatment arm

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.

Group Type: EXPERIMENTAL

BIIB132

Intervention Type: DRUG

Administered as specified in the treatment arm

BIIB132-Matching Placebo

Intervention Type: DRUG

Administered as specified in the treatment arm

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.

Group Type: EXPERIMENTAL

BIIB132

Intervention Type: DRUG

Administered as specified in the treatment arm

BIIB132-Matching Placebo

Intervention Type: DRUG

Administered as specified in the treatment arm

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.

Group Type: EXPERIMENTAL

BIIB132

Intervention Type: DRUG

Administered as specified in the treatment arm

BIIB132-Matching Placebo

Intervention Type: DRUG

Administered as specified in the treatment arm

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.

Group Type: EXPERIMENTAL

BIIB132

Intervention Type: DRUG

Administered as specified in the treatment arm

BIIB132-Matching Placebo

Intervention Type: DRUG

Administered as specified in the treatment arm

Interventions

BIIB132

Administered as specified in the treatment arm

Intervention Type: DRUG

BIIB132-Matching Placebo

Administered as specified in the treatment arm

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biogen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Biogen

Locations

University of California - Los Angeles

Los Angeles, California, United States

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

UniversitaetsklinikumTübingen Neurologische Universitätsklinik

Tübingen, Baden-Wurttemberg, Germany

Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)

Bonn, North Rhine-Westphalia, Germany

Universitaetsklinikum Essen Klinik für Neurologie

Essen, North Rhine-Westphalia, Germany

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Universitair Medisch Centrum Groningen (UMCG)

Groningen, , Netherlands

Radboudumc

Nijmegen, , Netherlands

Centro Hospitalar de Lisboa Norte

Lisbon, , Portugal

Centro Hospitalar do Porto

Porto, , Portugal

University College London Hospital (UCLH)

London, Greater London, United Kingdom

Churchill Hospital

Oxford, Oxfordshire, United Kingdom

Countries

United States; Germany; Israel; Netherlands; Portugal; United Kingdom

Other Identifiers

2021-002223-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

260SA101

Identifier Type: -

Identifier Source: org_study_id