Study of ARO-ATXN2 Injection in Adults With Spinocerebellar Ataxia Type 2

Phase 1

Recruiting

• Conditions: Spinocerebellar Ataxia Type 2
• Interventions: Drug: ARO-ATXN2 Injection; Drug: Placebo

• Registration Number: NCT06672445
• Lead Sponsor: Arrowhead Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-01
• Study First Submitted QC: 2024-11-01
• Study First Posted: 2024-11-04
• Study Start: 2024-12-17
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-13
• Last Update Posted: 2025-03-14
• Primary Completion: 2026-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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
• Coagulation parameters within normal ranges at Screening
• 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
• Presence of an implanted shunt for drainage of CSF or an implanted central nervous system (CNS) catheter

Note: Additional inclusion/exclusion criteria may apply per protocol.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARO-ATXN2	ARO-ATXN2 Injection	ARO-ATXN2 Injection
Placebo	Placebo	(0.9% NaCl)

Primary Outcome Measures

Name	Time	Method
Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time	Through End of Study (EOS), Day 253

Secondary Outcome Measures

Name	Time	Method
Change from Baseline in Cell Count in CSF Over Time	Baseline through End of Study (EOS), Day 253 or until ATXN2 protein levels are ≥ 50% of predose Baseline
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 or until ATXN2 protein levels are ≥ 50% of predose Baseline
Change from Baseline in Glucose in CSF Over Time	Baseline through End of Study (EOS), Day 253 or until ATXN2 protein levels are ≥ 50% of predose Baseline

Trial Locations

Locations (3)

Research Site; 🇳🇿 Christchurch, New Zealand

Research Site 2; 🇨🇦 Montréal, Quebec, Canada

Research Site 1; 🇨🇦 Montréal, Quebec, Canada