Spinocerebellar Ataxia Type 2
Conditions
Brief summary
Adult participants with spinocerebellar ataxia type 2 (SCA2) who carry ≥33 cytosine, adenine, guanine (CAG) repeats in the ATXN2 gene, and who have met all protocol eligibility criteria will be randomized to receive a single dose of ARO-ATXN2 or placebo and be evaluated for safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters.
Interventions
DRUGARO-ATXN2 Injection
single dose of ARO-ATXN2 by intrathecal (IT) administration
DRUGPlacebo
calculated volume to match active treatment by IT administration
Sponsors
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Non-pregnant, non-lactating * Diagnosis of symptomatic SCA2 and ≥33 CAG repeats in the ATXN2 gene based on source verifiable medical records or genetic testing at Screening * Scale of Assessment and Rating of Ataxia (SARA) score ≤14 * Subjects of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later
Exclusion criteria
* Uncontrolled hypertension (blood pressure \>160/100 mmHg) * History of having received stem cell therapy * Clinically significant cardiac, liver, or renal disease * Human immunodeficiency virus (HIV) infection (seropositive at Screening) * Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at Screening * Intellectual disability or significant behavioral neuropsychiatric manifestation * Any contraindications to lumbar puncture, including INR \>1.4, platelet count \<100,000, and use of anticoagulant or antiplatelet medications that cannot be safely interrupted * Presence of an implanted shunt for drainage of CSF or an implanted central nervous system (CNS) catheter Note: Additional inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time | Through End of Study (EOS), Day 253 |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) of ARO-ATXN2: Maximum Observed Plasma Concentration (Cmax) | Through 24 hours post-dose |
| PK of ARO-ATXN2: Time to Maximum Observed Plasma Concentration (Tmax) | Through 24 hours post-dose |
| PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24) | Through 24 hours post-dose |
| PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quatifiable Plasma Concentration (AUClast) | Through 24 hours post-dose |
| PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf) | Through 24 hours post-dose |
| PK of ARO-ATXN2: Elimination Half-life (t1/2) | Through 24 hours post-dose |
| PK of ARO-ATXN2: Apparent Systemic Clearance (CL/F) | Through 24 hours post-dose |
| PK of ARO-ATXN2: Recovery of Unchanged Drug Excreted in Urine (Ae) | Through 24 hours post-dose |
| PK of ARO-ATXN2: Renal Clearance (CLr) | Through 24 hours post-dose |
| Percentage of Administered Drug Recovered in Urine | Through 24 hours post-dose |
| Change from Baseline in Total Protein in Cerebral Spinal Fluid (CSF) Over Time | Baseline through End of Study (EOS), Day 253 |
| Change from Baseline in Glucose in CSF Over Time | Baseline through End of Study (EOS), Day 253 |
| Change from Baseline in Cell Count in CSF Over Time | Baseline through End of Study (EOS), Day 253 |
Countries
Australia, Canada, France, Germany, Italy, New Zealand, Spain, Taiwan
Outcome results
None listed