Spinocerebellar Ataxia Type 3Phase 1NCT05160558
A Pharmacokinetics and Safety Study of BIIB132 in Adults With Spinocerebellar Ataxia 3
A Phase 1 study testing BIIB132 in people with Spinocerebellar Ataxia Type 3, run by Biogen at 20 sites in 6 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Spinocerebellar Ataxia Type 3
- What is being tested?
- BIIB132
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 20 sitesin 6 countries
- Study dates
- 2 Feb 2022to 25 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
20 sites in 6 countries.
20 sites in 6 countries
United States10 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Florida, Center for Movement Disorders
Gainesville, Florida, 32610
Houston Methodist Research Institute
Houston, Texas, 77030
University of California - Los Angeles
Los Angeles, California, 90035
Columbia Univeristy Medical Center
New York, New York, 10032
Pennsylvania Neurological Institute
Philadelphia, Pennsylvania, 19107
University of California San Francisco
San Francisco, California, 94143
University of Washington
Seattle, Washington, 98195
Washington University
St Louis, Missouri, 63110
Movement Disorder Center Florida
Tampa, Florida, 33612
Germany3 sites
Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
Bonn, North Rhine-Westphalia, 53127
Universitaetsklinikum Essen Klinik für Neurologie
Essen, North Rhine-Westphalia, 45122
UniversitaetsklinikumTübingen Neurologische Universitätsklinik
Tübingen, Baden-Wurttemberg, 72076
Netherlands2 sites
Universitair Medisch Centrum Groningen (UMCG)
Groningen, 9713 AG
Radboudumc
Nijmegen, 6525 GA
Portugal2 sites
Centro Hospitalar de Lisboa Norte
Lisbon, 1649-035
Centro Hospitalar do Porto
Porto, 4099-001
United Kingdom2 sites
University College London Hospital (UCLH)
London, Greater London, WC1N 3BG
Churchill Hospital
Oxford, Oxfordshire, OX3 7LJ
About this study
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
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.
Read the 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
- Being tested
- BIIB132, BIIB132-Matching Placebo
- Medical subject headings
- Machado-Joseph Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIIB132Drug
Administered as specified in the treatment arm
BIIB132-Matching PlaceboDrug
Administered as specified in the treatment arm
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: BIIB132; Drug: BIIB132-Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Screening to Day 267
Secondary outcomes (6)
Area Under the Concentration-Time Curve (AUC) of BIIB132
Measured: 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
Measured: 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
Measured: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Maximum Observed Concentration (Cmax) of BIIB132
Measured: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Time to Reach Maximum Observed Concentration (Tmax) of BIIB132
Measured: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Elimination Half-Life (t½) of BIIB132
Measured: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2021
- Study start2 Feb 2022
- Primary completion25 Jul 2023
- Study completion25 Jul 2023
Why it stopped: Sponsor's Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinocerebellar Ataxia Type 3Studies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05160558
- Sponsor's protocol ID
- 260SA101
- Other IDs
- 2021-002223-37
- Status last verified
- Aug 2023
- First submitted
- 7 Dec 2021
- Last updated
- 4 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05160558
- Acronym / sponsor ID
- 260SA101
- Conditions
- Spinocerebellar Ataxia Type 3
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's Decision
- Enrolment
- 8 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2022 (actual)
- Primary completion
- 25 Jul 2023 (actual)
- Study completion
- 25 Jul 2023 (actual)
- First posted
- 16 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: BIIB132 Dose 1 or Matching Placebo | Experimental | Drug: BIIB132, Drug: BIIB132-Matching PlaceboParticipants will be randomized to receive BIIB132 Dose 1 or matching placebo, intrathecally (IT), every 4 weeks (Q4W), up to Day 85. |
| Cohort 2: BIIB132 Dose 2 or Matching Placebo | Experimental | Drug: BIIB132, Drug: BIIB132-Matching PlaceboParticipants will be randomized to receive BIIB132 Dose 2 or matching placebo, IT, Q4W, up to Day 85. |
| Cohort 3: BIIB132 Dose 3 or Matching Placebo | Experimental | Drug: BIIB132, Drug: BIIB132-Matching PlaceboParticipants will be randomized to receive BIIB132 Dose 3 or matching placebo, IT, Q4W, up to Day 85. |
| Cohort 4: BIIB132 Dose 4 or Matching Placebo | Experimental | Drug: BIIB132, Drug: BIIB132-Matching PlaceboParticipants will be randomized to receive BIIB132 Dose 4 or matching placebo, IT, Q4W, up to Day 85. |
| Cohort 5: BIIB132 Dose 5 or Matching Placebo | Experimental | Drug: BIIB132, Drug: BIIB132-Matching PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BIIB132Administered as specified in the treatment arm | Drug | 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 PlaceboAdministered as specified in the treatment arm | Drug | 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 |
Primary outcome
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.
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.
6 secondary outcomes
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
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
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
Maximum Observed Concentration (Cmax) of BIIB132
Time frame: 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
Elimination Half-Life (t½) of BIIB132
Time frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Results and safety
The study was stopped early (reason given: Sponsor's Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
20 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BIIB132 in people with Spinocerebellar Ataxia Type 3, run by Biogen at 20 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Germany, Netherlands, Portugal, United Kingdom and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor's Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events (AEs) (time frame: Day 1 to Day 267). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.