NCT07378644

Study to Evaluate the Pharmacodynamics, Safety and Efficacy of SKY-0515 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: 400 (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 study is a randomized, double-blind, placebo-controlled trial conducted across multiple sites. This clinical trial aims to evaluate the safety, pharmacodynamics, and efficacy of SKY-0515, a novel, orally administered small molecule. Huntington's Disease (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, 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. 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). Safety and efficacy will be evaluated through blood tests, imaging (MRI), and clinical assessments, including the Unified Huntington's Disease Rating Scale (UHDRS).

Conditions

• Huntington Disease

Interventions

Type	Name	Description
DRUG	SKY-0515	Type: Small molecule Dosage Level(s): Low, mid, high Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 18 months Use: Experimental
DRUG	SKY-0515 Placebo	Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 18 months Use: Experimental

Timeline

• Start date: 2026-01-06
• Primary completion: 2028-12-01
• Completion: 2029-08-01
• First posted: 2026-01-30
• Last updated: 2026-01-30

Locations

2 sites across 1 country: Georgia