Clinical trial NCT05160558: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Spinocerebellar Ataxia Type 3
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2021-12-16
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Day 1 to Day 267
measure: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Screening to Day 267
Secondary outcomes:
measure: Area Under the Concentration-Time Curve (AUC) of BIIB132
timeFrame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
measure: Area Under the Concentration Versus Time Curve, from Time of Dosing (Time = 0) to Infinity (AUCinf) of BIIB132
timeFrame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
measure: Area Under the Concentration Versus Time Curve, from Time of Dosing (Time = 0) to Time of the Last Measurable Effect (AUClast) of BIIB132
timeFrame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
measure: Maximum Observed Concentration (Cmax) of BIIB132
timeFrame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
measure: Time to Reach Maximum Observed Concentration (Tmax) of BIIB132
timeFrame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
measure: Elimination Half-Life (t½) of BIIB132
timeFrame: Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California - Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Gainesville
country: United States
facility: University of Florida, Center for Movement Disorders
state: Florida
city: Tampa
country: United States
facility: Movement Disorder Center Florida
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Columbia Univeristy Medical Center
state: New York
city: Philadelphia
country: United States
facility: Pennsylvania Neurological Institute
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Tuebingen
country: Germany
facility: UniversitaetsklinikumTübingen Neurologische Universitätsklinik
state: Baden Wuerttemberg
city: Bonn
country: Germany
facility: Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)
state: Nordrhein Westfalen
city: Essen
country: Germany
facility: Universitaetsklinikum Essen Klinik für Neurologie
state: Nordrhein Westfalen
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen (UMCG)
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto
city: London
country: United Kingdom
facility: University College London Hospital (UCLH)
state: Greater London
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: Oxfordshire
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: