ARO-ATXN2 for Spinocerebellar Ataxias

Recruiting at 5 trial locations

Overseen By Medical Monitor

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Arrowhead Pharmaceuticals

Disqualifiers: Uncontrolled hypertension, Cardiac, Liver, Renal, others

Compensation: Varies

Number of Visits: 1

Duration: 1 day

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

What data supports the effectiveness of the drug ARO-ATXN2 Injection for treating Spinocerebellar Ataxias?

Research on similar treatments, like antisense oligonucleotides (ASOs) targeting the ATXN2 gene in mouse models, shows promise in improving motor function and reducing disease protein levels, suggesting potential effectiveness for ARO-ATXN2 in treating Spinocerebellar Ataxias. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults with spinocerebellar ataxia type 2 (SCA2) who have a specific genetic marker (≥33 CAG repeats in the ATXN2 gene). Participants should not be pregnant or breastfeeding, must have a SARA score ≤14 indicating their disease severity, and normal coagulation levels. They must agree to use effective contraception during the study and for 90 days after.

Inclusion Criteria

Non-pregnant, non-lactating

Scale of Assessment and Rating of Ataxia (SARA) score ≤14

Coagulation parameters within normal ranges at Screening

Exclusion Criteria

I have a serious heart, liver, or kidney condition.

Human immunodeficiency virus (HIV) infection (seropositive at Screening)

Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at Screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of ARO-ATXN2 or placebo and are evaluated for safety, tolerability, pharmacokinetics, and pharmacodynamics

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• ARO-ATXN2 Injection

Trial Overview The trial is testing ARO-ATXN2 Injection versus a placebo in individuals with SCA2. After receiving one dose, participants will be monitored to assess how safe and tolerable the drug is, as well as its effects on the body (pharmacokinetics) and on the disease's progression (pharmacodynamics).

Participant Groups

Group I: ARO-ATXN2 Experimental Treatment 1 Intervention

ARO-ATXN2 Injection

Group II: Placebo Placebo Group 1 Intervention

(0.9% NaCl)

Who Is Running the Clinical Trial?

Arrowhead Pharmaceuticals

Lead Sponsor

Trials

45

Recruited

6,200+

Findings from Research

In a study involving 12 adult rhesus macaques, a viral vector delivering RNA interference targeting the ATXN1 gene successfully reduced ATXN1 mRNA levels by over 30% in key brain regions, indicating a potential therapeutic approach for spinocerebellar ataxia type 1.

The treatment was well tolerated with no clinical complications observed, suggesting that this method of gene silencing could be safely translated into clinical applications for patients with this neurodegenerative disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broad distribution of ataxin 1 silencing in rhesus cerebella for spinocerebellar ataxia type 1 therapy. Keiser, MS., Kordower, JH., Gonzalez-Alegre, P., et al.[2018]

In a study of three patients with episodic ataxia type 2 (EA2), the potassium channel blocker 4-aminopyridine (4-AP) effectively prevented ataxia attacks, suggesting a new treatment option for this condition.

The beneficial effects of 4-AP may be linked to its ability to improve the functioning of Purkinje cells, which are crucial for motor coordination, and symptoms returned when treatment was stopped, indicating the need for ongoing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of episodic ataxia type 2 with the potassium channel blocker 4-aminopyridine. Strupp, M., Kalla, R., Dichgans, M., et al.[2019]

A potential RNA-targeted therapy using antisense oligonucleotide ASO7 effectively reduced ATXN2 gene expression in mouse models of spinocerebellar ataxia type 2 (SCA2), leading to delayed onset of disease symptoms and improved motor function.

ASO7 treatment normalized the firing frequency of Purkinje cells and protein levels related to SCA2, demonstrating its efficacy even when administered after the onset of motor symptoms, suggesting a promising approach for neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. Scoles, DR., Meera, P., Schneider, MD., et al.[2022]

Antisense oligonucleotides (ASOs) targeting the ATXN3 gene showed promising results in reducing disease protein levels by over 50% in specific brain regions of SCA3 mouse models, indicating potential efficacy in treating this neurodegenerative disorder.

The treatment with ASOs did not cause any signs of inflammation in the brain, suggesting that this approach could be safe and well-tolerated, paving the way for future preventative therapies for SCA3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Antisense Oligonucleotides Targeting ATXN3 in SCA3 Mouse Models. Moore, LR., Rajpal, G., Dillingham, IT., et al.[2020]

In a study of 10 children with acute cerebellar ataxia, brain perfusion SPECT imaging revealed abnormalities in 7 cases, including cerebellar hypoperfusion and cortical involvement, which were not detected by CT or MRI scans.

The severity of the SPECT findings was significantly correlated with the clinical severity and recovery time of the ataxia, indicating that SPECT imaging can provide important prognostic information for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tc-99m HMPAO brain SPECT imaging in children with acute cerebellar ataxia. Hung, PL., Huang, SH., Huang, CC., et al.[2016]

References

1. England pubmed.ncbi.nlm.nih.gov

Broad distribution of ataxin 1 silencing in rhesus cerebella for spinocerebellar ataxia type 1 therapy. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of episodic ataxia type 2 with the potassium channel blocker 4-aminopyridine. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Antisense oligonucleotide therapy for spinocerebellar ataxia type 2. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Antisense Oligonucleotides Targeting ATXN3 in SCA3 Mouse Models. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Tc-99m HMPAO brain SPECT imaging in children with acute cerebellar ataxia. [2016]