Study to Evaluate the Pharmacodynamics, Safety and Efficacy of SKY-0515 in Participants With Huntington's Disease (FALCON-HD)

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

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: Recruiting
• Conditions: Huntington Disease
• Intervention / Treatment: Drug: SKY-0515; Drug: SKY-0515 Placebo

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).

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Study Director, MD; Phone Number: 6178580041; Email: sky0515trials@skyhawktx.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1056 AB
    • Recruiting
    • CINME Centro de Investigaciones Metabolicas
    • Contact: Principal Investigator; Phone Number: 0800-345-0697
• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04038002
      • Not yet recruiting
      • PSEG Centro de Pesquisa Clínica
      • Contact: Prinicipal Investigator; Phone Number: (11) 5572-4555
• Georgia
  • Tbilisi, Georgia
    • Recruiting
    • Pineo Medical Ecosystem
    • Contact: Sophia Sopromadze, MD; Phone Number: +995 599 360 430; Email: sophias@pineo.ge
    • Principal Investigator: Sophia Sopromadze, MD
  • Tbilisi, Georgia
    • Recruiting
    • Simon Khechinashvili University Hospital
    • Contact: Irine Khatiashvili, MD, Ph.D; Phone Number: +995577786578; Email: irenekhat@yahoo.com
    • Principal Investigator: Irine Khatiashvili, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 25 years or older.
• Huntington's Disease confirmed through genetic testing, with a specific change in exon 1 of the HTT gene (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 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.
• Agree to sign a consent form and follow the study's rules and schedule.

Exclusion Criteria:

• Other Serious health problems or brain/spinal issues that could interfere with the study or make procedures unsafe.
• Conditions that interfere with protocol-specified assessments, like an implanted medical device or difficulty getting an MRI.
• Cancer, except for some types of skin cancer, or a history of cancer in the last five years.
• Severe allergies or have reacted badly to similar drugs in the past.
• Taking medications or treatments that might interfere with the study.
• Participated in another study or taken experimental drugs in the last two months (or longer for some drugs).
• Any kind of gene therapy.
• History of suicidal thoughts, severe depression, or have attempted suicide in the past year.
• Liver function tests show significant abnormalities.
• Positive for hepatitis B, hepatitis C, or HIV.
• Pregnancy, breastfeeding, or planning to become pregnant during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Comparator (1); Dosage Level(s): Low Dose	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
Active Comparator: Active Comparator (2); Dosage Level(s): Mid Dose	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
Active Comparator: Active Comparator (3); Dosage Level(s): High Dose	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
Placebo Comparator: Placebo Comparator (4); Matching placebo once daily oral	Drug: SKY-0515 Placebo; Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 18 months Use: Experimental

What is the study measuring?

Primary 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.	72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 score is 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.	72 weeks
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).	72 weeks
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.	72 weeks
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.	72 weeks
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.	72 weeks

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): January 6, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: January 13, 2026
• First Submitted That Met QC Criteria: January 22, 2026
• First Posted (Actual): January 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: mRNA; Huntington Disease; Neurodegenerative; HTT; Splicing; Skyhawk; SKY-0515; Mutant Huntingtin protein
• 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-0515-004-WW

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