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

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ClinicalTrials.gov Identifier: NCT05160558
Recruitment Status : Recruiting
First Posted : December 16, 2021
Last Update Posted : January 12, 2023
Sponsor:
Information provided by (Responsible Party):
Biogen

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.

Condition or disease Intervention/treatment Phase
Spinocerebellar Ataxia Type 3 Drug: BIIB132 Drug: BIIB132-Matching Placebo Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : February 2, 2022
Estimated Primary Completion Date : December 12, 2025
Estimated Study Completion Date : December 12, 2025


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Maximum Observed Concentration (Cmax) of BIIB132 [ Time Frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85 ]
  5. 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 ]
  6. Elimination Half-Life (t½) of BIIB132 [ Time Frame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05160558


Contacts
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Contact: US Biogen Clinical Trial Center 866-633-4636 clinicaltrials@biogen.com
Contact: Global Biogen Clinical Trial Center clinicaltrials@biogen.com

Locations
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Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT05160558    
Other Study ID Numbers: 260SA101
2021-002223-37 ( EudraCT Number )
First Posted: December 16, 2021    Key Record Dates
Last Update Posted: January 12, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Machado-Joseph Disease
Ataxia
Cerebellar Ataxia
Spinocerebellar Ataxias
Spinocerebellar Degenerations
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn