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

August 3, 2023 updated by: Biogen

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants with Adverse Events (AEs)
Time Frame: 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.
Day 1 to Day 267
Number of Participants with Serious Adverse Events (SAEs)
Time Frame: 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.
Screening to Day 267

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
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
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
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
Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
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
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
Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Biogen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Biogen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 2, 2022

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 25, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 25, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 7, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 7, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 16, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 4, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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