Clinical trial NCT06672445: Study of ARO-ATXN2 Injection in Adults With Spinocerebellar Ataxia Type 2
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Spinocerebellar Ataxia Type 2
Lead sponsor: Arrowhead Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-11-04
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time
timeFrame: Through End of Study (EOS), Day 253
Secondary outcomes:
measure: Pharmacokinetics (PK) of ARO-ATXN2: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ATXN2: Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quatifiable Plasma Concentration (AUClast)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ATXN2: Elimination Half-life (t1/2)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ATXN2: Apparent Systemic Clearance (CL/F)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ATXN2: Recovery of Unchanged Drug Excreted in Urine (Ae)
timeFrame: Through 24 hours post-dose
measure: PK of ARO-ATXN2: Renal Clearance (CLr)
timeFrame: Through 24 hours post-dose
measure: Percentage of Administered Drug Recovered in Urine
timeFrame: Through 24 hours post-dose
measure: Change from Baseline in Total Protein in Cerebral Spinal Fluid (CSF) Over Time
timeFrame: Baseline through End of Study (EOS), Day 253 or until ATXN2 protein levels are ≥ 50% of predose Baseline
measure: Change from Baseline in Glucose in CSF Over Time
timeFrame: Baseline through End of Study (EOS), Day 253 or until ATXN2 protein levels are ≥ 50% of predose Baseline
measure: Change from Baseline in Cell Count in CSF Over Time
timeFrame: Baseline through End of Study (EOS), Day 253 or until ATXN2 protein levels are ≥ 50% of predose Baseline
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Research Site
state: New South Wales
city: Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Montréal
country: Canada
facility: Research Site 2
state: Quebec
city: Montréal
country: Canada
facility: Research Site 1
state: Quebec
city: Auckland
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
Study officials:
References: