ARO-ATXN2 for Spinocerebellar Ataxias

Recruiting at 10 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new injection treatment called ARO-ATXN2 for individuals with spinocerebellar ataxia type 2 (SCA2), a condition affecting balance and coordination. The research focuses on the treatment's safety, tolerability, and behavior in the body. Participants will receive either the actual treatment or a placebo (a harmless substance resembling the treatment but without active ingredients) to compare results. Suitable participants should exhibit SCA2 symptoms and possess a specific genetic marker (33 or more CAG repeats in the ATXN2 gene), confirmed by medical records or genetic testing. As a Phase 1 trial, this research aims to understand how the treatment works in people, with participants among the first to receive it.

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.

Is there any evidence suggesting that ARO-ATXN2 is likely to be safe for humans?

Research has shown that ARO-ATXN2 is being developed to reduce the amount of Ataxin-2 protein, which is linked to spinocerebellar ataxia type 2 (SCA2), a condition affecting movement and coordination.

Currently, there is limited information on the safety of ARO-ATXN2 for people, as it is being tested in early human trials. This phase of research primarily focuses on assessing safety and treatment tolerance. These trials often start with healthy volunteers to gather initial safety data.

Since ARO-ATXN2 is in early testing, detailed safety data may not yet be fully available. However, its testing in humans suggests that some initial safety has been established. As research progresses, more information on side effects and treatment tolerance will likely emerge. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

ARO-ATXN2 is unique because it offers a new approach to treating Spinocerebellar Ataxias by targeting the underlying genetic causes. Unlike current treatments that mainly address symptoms, ARO-ATXN2 uses RNA interference technology to potentially reduce the production of harmful proteins linked to the disease. Researchers are excited about this treatment because it could slow down disease progression rather than just managing symptoms, offering hope for a more effective long-term solution.

What evidence suggests that ARO-ATXN2 might be an effective treatment for spinocerebellar ataxia type 2?

Research has shown that ARO-ATXN2, which participants in this trial may receive, is designed to lower the amount of the Ataxin-2 protein. This protein is linked to the development of spinocerebellar ataxia type 2 (SCA2), a condition affecting movement and coordination. By reducing Ataxin-2, ARO-ATXN2 might slow the progression of SCA2 symptoms. Although limited information exists from human studies, this treatment targets a known cause of the disease, making it a promising option for people with SCA2. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

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

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06672445/study-of-aro-atxn2-injection-in-adults-with-spinocerebellar-ataxia-type-2

Study of ARO-ATXN2 Injection in Adults With ... A single dose of ARO-ATXN2 or placebo and be evaluated for safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06672445?term=AREA%5BConditionSearch%5D(Spinocerebellar%20Ataxia%20Type%202)&rank=4

NCT06672445 | Study of ARO-ATXN2 Injection in Adults ... A type of clinical study in which participants are identified as belonging to study groups and are assessed for biomedical or health outcomes. Participants may ...

3. youtube.com youtube.com/watch?v=0dPf9ijSvsM

AROATXN2-1001: A Phase 1 Placebo-controlled Study to ... This webinar provided information about Arrowhead Pharmaceuticals' ongoing Phase 1 study of ARO-ATXN2 in patients with Spinocerebellar Ataxia ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06672445

NCT06672445 | Study of ARO-ATXN2 Injection in Adults ... 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 ...

5. ataxia.org ataxia.org/study/aroatxn2-1001/

AROATXN2-1001 ARO-ATXN2 is a medication designed to reduce the level of the Ataxin-2 protein, which has been implicated in the development of SCA2.

6. arrowheadpharma.com arrowheadpharma.com/pipeline/

Our Pipeline A Phase 1/2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-INHBE in Adult Volunteers With Obesity With and Without ...

7. ctv.veeva.com ctv.veeva.com/study/study-of-aro-atxn2-injection-in-adults-with-spinocerebellar-ataxia-type2

Study of ARO-ATXN2 Injection in Adults With Spinocerebellar ... Randomized to receive a single dose of ARO-ATXN2 or placebo and be evaluated for safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters.