NCT06873334

Study of SKY-0515 for Safety, Efficacy, and Pharmacodynamics in Participants With Huntington's Disease

A Phase 2/3 Randomized, Double Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Pharmacodynamics, Safety and Efficacy of SKY-0515 in Participants With Huntington's Disease

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: Skyhawk Therapeutics, Inc. · Industry
• Sex: All
• Age: 25 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to test if the drug SKY-0515, an oral medication, can lower harmful proteins linked to Huntington's Disease (HD) and improve the symptoms of participants with HD. This study includes men and women aged 25 and older who have HD confirmed by genetic testing and meet certain requirements for physical ability and independence.

Detailed description

This clinical trial aims to evaluate the safety, pharmacodynamics, and efficacy of SKY-0515, a novel, orally-administered small molecule mRNA-splicing modulator for treating Huntington's Disease (HD). HD is a rare, inherited neurodegenerative condition caused by a mutation in the huntingtin (HTT) gene, resulting in excessive production of mutant huntingtin (mHTT) protein, which damages nerve cells and leads to progressive motor, cognitive, and psychiatric symptoms. SKY-0515 is designed to reduce mHTT protein levels by lowering of HTT messenger RNA (mRNA) through a splicing mechanism, leading to a decrease in both wild-type and mutant forms of HTT protein. Additionally, the drug lowers postmeiotic segregation 1 (PMS1) protein, which plays a role in somatic CAG repeat expansion-a key driver of HD progression. In early studies, SKY-0515 has reduced HTT and PMS1 mRNA levels in a dose-dependent manner, with favorable safety and tolerability profiles in healthy volunteers. This study is a randomized, double-blind, placebo-controlled, trial conducted at multiple sites. Participants must be aged 25 or older, have genetically confirmed HD (CAG repeat length ≥ 40), and meet specific functional and motor criteria. They will be assigned randomly to one of four treatment arms (three doses of SKY-0515 and one placebo group) in a 1:1:1:1 ratio. The study is composed of three periods: 1. Screening Period (up to 4 weeks): Participants will undergo eligibility assessments. 2. Double-Blind Treatment Period (12 months): Participants will take SKY-0515 or a placebo once daily and undergo regular clinic visits for monitoring. Safety and efficacy will be evaluated through blood tests, imaging (MRI), and clinical assessments, including the Unified Huntington's Disease Rating Scale (UHDRS). 3. Follow-Up Period (4 weeks): After completing treatment, participants will be monitored for any remaining effects. An independent Data Safety Monitoring Board (DSMB) will oversee the trial to ensure participant safety. This study will assess: * Changes in levels of HTT proteins and other HD-related biomarkers. * Effects on HD-related brain atrophy and clinical features. * Long-term safety of SKY-0515.

Conditions

• Huntington Disease
• Huntingtons Disease

Interventions

Type	Name	Description
DRUG	SKY-0515	Study Drug Name (INN): SKY-0515 Type: Drug (small molecule) Dosage Level(s): Low, mid, high Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 12 months Use: Experimental Sourcing: SKY-0515 will be provided centrally by the Sponsor or subsidiary, or designee Packaging and Labeling: Study drug will be provided in blinded bottles labeled as required per country requirement. All packaging and labeling operations for the study drug will be performed according to current Good Manufacturing Practice for Medicinal Products and the relevant regulatory requirements.
DRUG	SKY-0515 Placebo	Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 12 months Use: Experimental Sourcing: SKY-0515 placebo will be provided centrally by the Sponsor or subsidiary, or designee Packaging and Labeling: Study drug will be provided in blinded bottles labeled as required per country requirement. All packaging and labeling operations for the study drug will be performed according to current Good Manufacturing Practice for Medicinal Products and the relevant regulatory requirements

Timeline

• Start date: 2025-05-27
• Primary completion: 2027-05-01
• Completion: 2027-12-01
• First posted: 2025-03-12
• Last updated: 2026-02-02

Locations

11 sites across 2 countries: Australia, New Zealand