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

Spinocerebellar Ataxia Type 3 Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05160558
• Other study ID #: 260SA101
• Secondary ID: 2021-002223-37
• Status: Terminated
• Phase: Phase 1
• Start date: February 2, 2022
• Est. completion date: July 25, 2023

Study information

• Verified date: August 2023
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). The secondary objective of this study is to characterize the multiple-dose pharmacokinetics (PK) of BIIB132 administered via IT injection to participants with SCA3.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: July 25, 2023
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Machado-Joseph Disease
• Spinocerebellar Ataxia Type 3
• Spinocerebellar Ataxias
• Spinocerebellar Degenerations

Intervention

Drug:
• BIIB132
Administered as specified in the treatment arm
• BIIB132-Matching Placebo
Administered as specified in the treatment arm

Locations

Country	Name	City	State
Germany	Deutsches Zentrum fuer Neurodegenerative Erkrankungen (DZNE)	Bonn	Nordrhein Westfalen
Germany	Universitaetsklinikum Essen Klinik für Neurologie	Essen	Nordrhein Westfalen
Germany	UniversitaetsklinikumTübingen Neurologische Universitätsklinik	Tuebingen	Baden Wuerttemberg
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Netherlands	Universitair Medisch Centrum Groningen (UMCG)	Groningen
Netherlands	Radboudumc	Nijmegen
Portugal	Centro Hospitalar de Lisboa Norte	Lisboa
Portugal	Centro Hospitalar do Porto	Porto
United Kingdom	University College London Hospital (UCLH)	London	Greater London
United Kingdom	Churchill Hospital	Oxford	Oxfordshire
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Florida, Center for Movement Disorders	Gainesville	Florida
United States	Houston Methodist Research Institute	Houston	Texas
United States	University of California - Los Angeles	Los Angeles	California
United States	Columbia Univeristy Medical Center	New York	New York
United States	Pennsylvania Neurological Institute	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	University of Washington	Seattle	Washington
United States	Movement Disorder Center Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

United States,  Germany,  Israel,  Netherlands,  Portugal,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 to Day 267
Primary	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.	Screening to Day 267
Secondary	Area Under the Concentration-Time Curve (AUC) of BIIB132		Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Secondary	Area Under the Concentration Versus Time Curve, from Time of Dosing (Time = 0) to Infinity (AUCinf) of BIIB132		Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Secondary	Area Under the Concentration Versus Time Curve, from Time of Dosing (Time = 0) to Time of the Last Measurable Effect (AUClast) of BIIB132		Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Secondary	Maximum Observed Concentration (Cmax) of BIIB132		Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Secondary	Time to Reach Maximum Observed Concentration (Tmax) of BIIB132		Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85
Secondary	Elimination Half-Life (t½) of BIIB132		Pre-dose and at multiple timepoints post-dose on Day 1 up to Day 85