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

A Phase 1 Placebo-Controlled Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-ATXN2 in Adult Subjects With Spinocerebellar Ataxia Type 2

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.

Study Overview

• Status: Recruiting
• Conditions: Spinocerebellar Ataxia Type 2
• Intervention / Treatment: Drug: ARO-ATXN2 Injection; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Monitor; Phone Number: 626-304-3400; Email: AROATXN2@arrowheadpharma.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2170
      • Recruiting
      • Research Site 8
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Research Site 7
• Canada
  • Edmonton, Canada, 8440
    • Recruiting
    • Research Site 9
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C1
      • Recruiting
      • Research Site 2
    • Montreal, Quebec, Canada, H3A 2B4
      • Recruiting
      • Research Site 1
• France
  • Paris
    • Paris, Paris, France, 75651
      • Recruiting
      • Research Site 15
• Germany
  • Baden-Wurttemberg
    • Tübingen, Baden-Wurttemberg, Germany, 72026
      • Recruiting
      • Research Site 13
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Recruiting
      • Research Site 14
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Research Site 16
• New Zealand
  • Auckland, New Zealand, 0622
    • Recruiting
    • Research Site 4
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Research Site 3
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Research Site 10
  • Barcelona, Spain, 08036
    • Recruiting
    • Research Site 11
  • Seville, Spain, 41013
    • Recruiting
    • Research Site 12
• Taiwan
  • Kaohsiung City, Taiwan, 833401
    • Recruiting
    • Research Site 5
  • Taipei, Taiwan, 112201
    • Recruiting
    • Research Site 6

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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/exclusion criteria may apply per protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; (0.9% NaCl)	Drug: Placebo; calculated volume to match active treatment by IT administration
Experimental: ARO-ATXN2; ARO-ATXN2 Injection	Drug: ARO-ATXN2 Injection; single dose of ARO-ATXN2 by intrathecal (IT) administration

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Arrowhead Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 1, 2024
• First Submitted That Met QC Criteria: November 1, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Dyskinesias; Cerebellar Diseases; Cerebellar Ataxia; Spinocerebellar Degenerations; Ataxia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Spinocerebellar Ataxias; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: AROATXN2-1001; UTN U111-1308 5875 (Other Identifier: WHO); 2024-514763-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes