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

Last updated: July 8, 2025
Sponsor: Skyhawk Therapeutics, Inc.
Overall Status: Active - Recruiting

Phase

2/3

Condition

Dyskinesias

Treatment

SKY-0515 Placebo

SKY-0515

Clinical Study ID

NCT06873334
SKY-0515-004-ANZ
  • Ages > 25
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • You must be 25 years or older.

  • You must have Huntington's Disease confirmed through genetic testing, with aspecific gene change (CAG repeat of 40 or more).

  • Total Functional Capacity (TFC) score of 10 or more).

  • Total Motor Score (TMS) of 6 or more).

  • Independence Score (IS) of 70 or more).

  • Women who can have children must have a negative pregnancy test before starting anduse two types of birth control during the study and for 30 days after the last doseof the study drug.

  • Men must agree to use birth control during the study and for 90 days after the lastdose.

  • You must agree to sign a consent form and follow the study's rules and schedule.

Exclusion

Exclusion Criteria:

  • You have other serious health problems or brain/spinal issues that could interferewith the study or make procedures unsafe.

  • You have a condition that interferes with protocol-specified assessments, like animplanted medical device or difficulty getting an MRI.

  • You have cancer, except for some types of skin cancer, or a history of cancer in thelast five years.

  • You have severe allergies or have reacted badly to similar drugs in the past.

  • You are taking medications or treatments that might interfere with the study.

  • You've been in another study or taken experimental drugs in the last two months (orlonger for some drugs).

  • You have had any kind of gene therapy.

  • You have a history of suicidal thoughts, severe depression, or have attemptedsuicide in the past year.

  • Your liver function tests show significant abnormalities.

  • You have tested positive for hepatitis B, hepatitis C, or HIV.

  • You are pregnant, breastfeeding, or planning to become pregnant during the study.

Study Design

Total Participants: 120
Treatment Group(s): 2
Primary Treatment: SKY-0515 Placebo
Phase: 2/3
Study Start date:
May 27, 2025
Estimated Completion Date:
December 31, 2027

Study 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.

Connect with a study center

  • John Hunter Hospital

    New Lambton Heights, New South Wales 2305
    Australia

    Site Not Available

  • Westmead Hospital

    Westmead, New South Wales 2145
    Australia

    Site Not Available

  • The University of Queensland

    Herston, Queensland 4006
    Australia

    Site Not Available

  • The University of Queensland - Royal Brisbane Womens Hospital

    Herston, Queensland 4006
    Australia

    Site Not Available

  • Flinders Medical Centre

    Adelaide, South Australia 5042
    Australia

    Active - Recruiting

  • Flinders Medical Centre

    Bedford Park, South Australia 5042
    Australia

    Site Not Available

  • Calvary Health Care Bethlehem

    Caulfield South, Victoria 3162
    Australia

    Active - Recruiting

  • The Royal Melbourne Hospital

    Parkville, Victoria 3050
    Australia

    Site Not Available

  • The Perron Institute for Neurology and Translational Science (Perron Institute)

    Nedlands, Western Australia 6009
    Australia

    Active - Recruiting

  • Auckland City Hospital

    Auckland, 1023
    New Zealand

    Site Not Available

  • Christchurch Neurology Trials Limited

    Christchurch, 8011
    New Zealand

    Site Not Available

  • Wellington Hospital

    Wellington, 6021
    New Zealand

    Site Not Available

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