An Extension of SKY-0515 in Participants With Huntington's Disease

An Open Label Extension of SKY-0515 in Participants With Huntington's Disease Who Completed a Prior SKY-0515 Treatment Study

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Huntington's Disease (HD)
• Intervention / Treatment: Drug: SKY-0515

Detailed Description

This is an OLE study to investigate the long-term safety, tolerability, and efficacy of SKY-0515 administered orally in participants with HD. To be eligible for this OLE study, participants must have completed dosing in a prior SKY-0515 treatment study and meet eligibility criteria for this study at an approved clinical study site. The study is comprised of an enrollment visit, a treatment period, and a follow-up visit. Throughout the study, participants will be evaluated as specified in the Schedule of Activities. At the enrollment visit (which may be the same as the last treatment visit of the prior study), participants will be consented to enter the OLE study and initiate open label treatment with 9 mg tablets of SKY-0515. Open label SKY-0515 will be self-administered daily (QD).

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Caulfield South, Victoria, Australia, 3162
      • Calvary Health Care Bethlehem
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Must have completed treatment in a prior SKY-0515 treatment study and, in the opinion of the Investigator, have been compliant with the prior SKY-0515 treatment protocol study procedures.
• Must be able and willing to meet all study requirements in the opinion of the Investigator including:
• Participants must be able to tolerate blood draws
• Willing and able to comply with all scheduled visits, treatment plans,laboratory tests and other study procedures
• Women who can have children must have a negative pregnancy test before starting and use two types of birth control during the study and for 30 days after the last dose of the study drug.
• Men must agree to use birth control during the study and for 90 days after the last dose.

Exclusion Criteria:

-Have any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 9mg dose; Drug: SKY-0515 Type: Small molecule Route of Administration: Oral Dosage Frequency: Once daily Duration: until study drug is approved or study is discontinued Use: Experimental

Drug: SKY-0515; Study Drug Name (INN): SKY-0515 Type: Drug (small molecule) Dosage Level(s): 9mg Route of Administration: Oral Dosage Frequency: Once daily Treatment Duration: until drug becomes commercially available or until the development of SKY-0515 is terminated by the Sponsor. 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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term safety and tolerability of SKY-0515	To investigate the long-term safety and tolerability of SKY-0515 through the Incidence, severity, and relationship of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) (including withdrawals due to TEAEs)	Continuously from enrollment to study completion or approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Z-score from the Composite Unified Huntington's Disease Rating Scale (cUHDRS)	cUHDRS includes the Total Functional Capacity (range, 0-13; higher score means better functioning), Total Motor Score (range, 0-124; higher score means worse motor severity), Symbol Digit Modality Test (range, 0-110, correctly paired numbers-symbols in 90 seconds; higher score means better cognitive performance), and Stroop Color and Word Test (range, 0-no max value, correctly read color words in 45 seconds; higher score means better cognitive performance) scores. A z-score for each test is calculated, which alone can be used to describe relationship between an individual's test score and the mean score of a target population. A z-score of 0 is the mean, and ±1 is 1 standard deviation from the mean. For cUHDRS, z-scores of each test are summed, whereby a higher cUHDRS score is better (score of -3.06-no max value) and a change of ≥1.2 is a meaningful worsening, shown to track functional decline.	Every 3 months for the first year, beginning with enrollment, then every six months for approximately 36 months.
Change from Baseline in Total Motor Score (TMS)	The total motor score (TMS) assessed motor features of HD with standardized ratings of oculomotor function, dysarthria, chorea, dystonia, gait, and postural stability. Some items (such as chorea and dystonia) required grading each extremity (face, bucco-oral-lingual, and trunk) separately. Eye movements require both horizontal and vertical grades. The total motor impairment scores was the sum of all the individual 31 motor sub-items (each rated from 0 to 4), with higher scores indicating more severe motor impairment than lower scores. The range of TMS is 0-124.	Every 3 months for the first year, beginning with enrollment, then every six months for approximately 36 months.
Change from Baseline in Total Functional Capacity (TFC)	TFC consists of five ordinally scaled items assessing a person's capacity with: (1) occupation; (2) financial affairs; (3) domestic responsibilities; (4) activities of daily living; and (5) independent living. Total score ranges from zero (worst) to 13 (best).	Every 3 months for the first year, beginning with enrollment, then every six months for approximately 36 months.
Change from Baseline in Independence Scale Score (IS)	The independence scale assesses independence on a 0 to 100 scale with higher scores indicating better functioning.	Every 3 months for the first year, beginning with enrollment, then every six months for approximately 36 months.
Change from Baseline in Symbol Digit Modalities Test (SDMT)	The SDMT assesses attention, visuoperceptual processing, working memory, and cognitive/psychomotor speed. The score is the number of correctly paired abstract symbols and specific numbers in 90 seconds with higher scores indicating better cognitive functioning.	Every 3 months for the first year, beginning with enrollment, then every six months for approximately 36 months.
Change from Baseline in the Stroop Color and Word Test (SCWT)	In the Stroop Color and Word Test (SCWT) the number of words and colors read correctly is counted, with a higher score indicating better cognitive performance scores. There is no upper limit for SWR as it is a time-based task. The lower limit (worst possible) however is 0; higher score is better meaning less severity.	Every 3 months for the first year, beginning with enrollment, then every six months for approximately 36 months.

Collaborators and Investigators

• Sponsor: Skyhawk Therapeutics, Inc.

Publications and helpful links

Helpful Links

• Skyhawk Therapeutics Website

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: April 3, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 17, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: SKY-0515
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Genetic Diseases, Inborn; Neurocognitive Disorders; Cognition Disorders; Dementia; Neurodegenerative Diseases; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Dyskinesias; Chorea; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Huntington Disease
• Other Study ID Numbers: SKY-0515-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No