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

NCT05160558 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 260SA1012021-002223-37
• Study Type: interventional
• Target: 8
• Locations: 6 countries
• Sites: 20

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.

Conditions

Spinocerebellar Ataxia Type 3

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

Study Arms (5)

Cohort 1: BIIB132 Dose 1 or Matching Placebo

EXPERIMENTAL

Participants will be randomized to receive BIIB132 Dose 1 or matching placebo, intrathecally (IT), every 4 weeks (Q4W), up to Day 85.

Drug: BIIB132; Drug: BIIB132-Matching Placebo

Cohort 2: BIIB132 Dose 2 or Matching Placebo

EXPERIMENTAL

Participants will be randomized to receive BIIB132 Dose 2 or matching placebo, IT, Q4W, up to Day 85.

Drug: BIIB132; Drug: BIIB132-Matching Placebo

Cohort 3: BIIB132 Dose 3 or Matching Placebo

EXPERIMENTAL

Participants will be randomized to receive BIIB132 Dose 3 or matching placebo, IT, Q4W, up to Day 85.

Drug: BIIB132; Drug: BIIB132-Matching Placebo

Cohort 4: BIIB132 Dose 4 or Matching Placebo

EXPERIMENTAL

Participants will be randomized to receive BIIB132 Dose 4 or matching placebo, IT, Q4W, up to Day 85.

Drug: BIIB132; Drug: BIIB132-Matching Placebo

Cohort 5: BIIB132 Dose 5 or Matching Placebo

EXPERIMENTAL

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; Drug: BIIB132-Matching Placebo

Interventions

BIIB132 DRUG

Administered as specified in the treatment arm

Cohort 1: BIIB132 Dose 1 or Matching Placebo; Cohort 2: BIIB132 Dose 2 or Matching Placebo; Cohort 3: BIIB132 Dose 3 or Matching Placebo; Cohort 4: BIIB132 Dose 4 or Matching Placebo; Cohort 5: BIIB132 Dose 5 or Matching Placebo

BIIB132-Matching Placebo DRUG

Administered as specified in the treatment arm

Cohort 1: BIIB132 Dose 1 or Matching Placebo; Cohort 2: BIIB132 Dose 2 or Matching Placebo; Cohort 3: BIIB132 Dose 3 or Matching Placebo; Cohort 4: BIIB132 Dose 4 or Matching Placebo; Cohort 5: BIIB132 Dose 5 or Matching Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

Study Sites (20)

University of California - Los Angeles

Los Angeles, California, 90035, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Florida, Center for Movement Disorders

Gainesville, Florida, 32610, United States

Location

Movement Disorder Center Florida

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Columbia Univeristy Medical Center

New York, New York, 10032, United States

Location

Pennsylvania Neurological Institute

Philadelphia, Pennsylvania, 19107, United States

Location

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

UniversitaetsklinikumTübingen Neurologische Universitätsklinik

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)

Bonn, North Rhine-Westphalia, 53127, Germany

Location

Universitaetsklinikum Essen Klinik für Neurologie

Essen, North Rhine-Westphalia, 45122, Germany

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Universitair Medisch Centrum Groningen (UMCG)

Groningen, 9713 AG, Netherlands

Location

Radboudumc

Nijmegen, 6525 GA, Netherlands

Location

Centro Hospitalar de Lisboa Norte

Lisbon, 1649-035, Portugal

Location

Centro Hospitalar do Porto

Porto, 4099-001, Portugal

Location

University College London Hospital (UCLH)

London, Greater London, WC1N 3BG, United Kingdom

Location

Churchill Hospital

Oxford, Oxfordshire, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Machado-Joseph Disease

Condition Hierarchy (Ancestors)

Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinocerebellar Degenerations; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Ataxia; Dyskinesias; Neurologic Manifestations; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: December 16, 2021
• Study Start: February 2, 2022
• Primary Completion: July 25, 2023
• Study Completion: July 25, 2023
• Last Updated: August 4, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

DE (3); US (10); PT (2); GB (2); IL (1); NL (2)