Back to resultsA Pharmacokinetics and Safety Study of BIIB132 in Adults With Spinocerebellar Ataxia 3
Primary Purpose
Spinocerebellar Ataxia Type 3
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
BIIB132
BIIB132-Matching Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Spinocerebellar Ataxia Type 3
Eligibility Criteria
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.
Sites / Locations
- University of California - Los Angeles
- University of California San Francisco
- University of Florida, Center for Movement Disorders
- Movement Disorder Center Florida
- Massachusetts General Hospital
- Washington University
- Columbia Univeristy Medical Center
- Pennsylvania Neurological Institute
- Houston Methodist Research Institute
- University of Washington
- UniversitaetsklinikumTübingen Neurologische Universitätsklinik
- Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
- Universitaetsklinikum Essen Klinik für Neurologie
- Tel Aviv Sourasky Medical Center
- Universitair Medisch Centrum Groningen (UMCG)
- Radboudumc
- Centro Hospitalar de Lisboa Norte
- Centro Hospitalar do Porto
- University College London Hospital (UCLH)
- Churchill Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
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
Arm Description
Participants will be randomized to receive BIIB132 Dose 1 or matching placebo, intrathecally (IT), every 4 weeks (Q4W), up to Day 85.
Participants will be randomized to receive BIIB132 Dose 2 or matching placebo, IT, Q4W, up to Day 85.
Participants will be randomized to receive BIIB132 Dose 3 or matching placebo, IT, Q4W, up to Day 85.
Participants will be randomized to receive BIIB132 Dose 4 or matching placebo, IT, Q4W, up to Day 85.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Area Under the Concentration-Time Curve (AUC) of BIIB132
Area Under the Concentration Versus Time Curve, from Time of Dosing (Time = 0) to Infinity (AUCinf) of BIIB132
Area Under the Concentration Versus Time Curve, from Time of Dosing (Time = 0) to Time of the Last Measurable Effect (AUClast) of BIIB132
Maximum Observed Concentration (Cmax) of BIIB132
Time to Reach Maximum Observed Concentration (Tmax) of BIIB132
Elimination Half-Life (t½) of BIIB132
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05160558
Brief Title
A Pharmacokinetics and Safety Study of BIIB132 in Adults With Spinocerebellar Ataxia 3
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Terminated
Why Stopped
Sponsor's Decision
Study Start Date
February 2, 2022 (Actual)
Primary Completion Date
July 25, 2023 (Actual)
Study Completion Date
July 25, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinocerebellar Ataxia Type 3
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: BIIB132 Dose 1 or Matching Placebo
Arm Type
Experimental
Arm Description
Participants will be randomized to receive BIIB132 Dose 1 or matching placebo, intrathecally (IT), every 4 weeks (Q4W), up to Day 85.
Arm Title
Cohort 2: BIIB132 Dose 2 or Matching Placebo
Arm Type
Experimental
Arm Description
Participants will be randomized to receive BIIB132 Dose 2 or matching placebo, IT, Q4W, up to Day 85.
Arm Title
Cohort 3: BIIB132 Dose 3 or Matching Placebo
Arm Type
Experimental
Arm Description
Participants will be randomized to receive BIIB132 Dose 3 or matching placebo, IT, Q4W, up to Day 85.
Arm Title
Cohort 4: BIIB132 Dose 4 or Matching Placebo
Arm Type
Experimental
Arm Description
Participants will be randomized to receive BIIB132 Dose 4 or matching placebo, IT, Q4W, up to Day 85.
Arm Title
Cohort 5: BIIB132 Dose 5 or Matching Placebo
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
BIIB132
Intervention Description
Administered as specified in the treatment arm
Intervention Type
Drug
Intervention Name(s)
BIIB132-Matching Placebo
Intervention Description
Administered as specified in the treatment arm
Primary Outcome Measure Information:
Title
Number of Participants with Adverse Events (AEs)
Description
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.
Time Frame
Day 1 to Day 267
Title
Number of Participants with Serious Adverse Events (SAEs)
Description
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.
Time Frame
Screening to Day 267
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
Maximum Observed Concentration (Cmax) of BIIB132
Time Frame
Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Title
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
Title
Elimination Half-Life (t½) of BIIB132
Time Frame
Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
University of California - Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90035
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
University of Florida, Center for Movement Disorders
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Movement Disorder Center Florida
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia Univeristy Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Pennsylvania Neurological Institute
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Houston Methodist Research Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
UniversitaetsklinikumTübingen Neurologische Universitätsklinik
City
Tuebingen
State/Province
Baden Wuerttemberg
ZIP/Postal Code
72076
Country
Germany
Facility Name
Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
City
Bonn
State/Province
Nordrhein Westfalen
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitaetsklinikum Essen Klinik für Neurologie
City
Essen
State/Province
Nordrhein Westfalen
ZIP/Postal Code
45122
Country
Germany
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Universitair Medisch Centrum Groningen (UMCG)
City
Groningen
ZIP/Postal Code
9713 AG
Country
Netherlands
Facility Name
Radboudumc
City
Nijmegen
ZIP/Postal Code
6525 GA
Country
Netherlands
Facility Name
Centro Hospitalar de Lisboa Norte
City
Lisboa
ZIP/Postal Code
1649-035
Country
Portugal
Facility Name
Centro Hospitalar do Porto
City
Porto
ZIP/Postal Code
4099-001
Country
Portugal
Facility Name
University College London Hospital (UCLH)
City
London
State/Province
Greater London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
Facility Name
Churchill Hospital
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
IPD Sharing URL
https://vivli.org/
Learn more about this trial
A Pharmacokinetics and Safety Study of BIIB132 in Adults With Spinocerebellar Ataxia 3
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