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

NCT07378644 | Recruiting Phase 2 DMC

• 1 other identifier: SKY-0515-004-WW
• Study Type: interventional
• Target: 400
• Locations: 3 countries
• Sites: 4

Brief 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.

Conditions

Huntington Disease

Keywords

SKY-0515; Skyhawk; HTT; Neurodegenerative; Huntington Disease; mRNA; Splicing; Mutant Huntingtin protein

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Change from Baseline in Total Motor Score (TMS)

  72 weeks

• Change from Baseline in Total Functional Capacity (TFC)

  72 weeks

• Change from Baseline in Independence Scale Score (IS)

  72 weeks

• Change from Baseline in Symbol Digit Modalities Test (SDMT)

  72 weeks

• Change from Baseline in the Stroop Color and Word Test (SCWT)

  72 weeks

Study Arms (4)

Active Comparator (1)

ACTIVE COMPARATOR

Dosage Level(s): Low Dose

Drug: SKY-0515

Active Comparator (2)

ACTIVE COMPARATOR

Dosage Level(s): Mid Dose

Drug: SKY-0515

Active Comparator (3)

ACTIVE COMPARATOR

Dosage Level(s): High Dose

Drug: SKY-0515

Placebo Comparator (4)

PLACEBO COMPARATOR

Matching placebo once daily oral

Drug: SKY-0515 Placebo

Interventions

SKY-0515 DRUG

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 (1); Active Comparator (2); Active Comparator (3)

SKY-0515 Placebo DRUG

Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 18 months Use: Experimental

Placebo Comparator (4)

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Skyhawk Therapeutics, Inc.: lead

Study Sites (4)

CINME Centro de Investigaciones Metabólicas

Buenos Aires, C1056 AB, Argentina

RECRUITING

PSEG Centro de Pesquisa Clinica

São Paulo, São Paulo, 04038002, Brazil

NOT YET RECRUITING

Pineo Medical Ecosystem

Tbilisi, Georgia

RECRUITING

Simon Khechinashvili University Hospital

Tbilisi, Georgia

RECRUITING

Related Links

• Skyhawk Therapeutics Website

MeSH Terms

Conditions

Huntington Disease

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Chorea; Dyskinesias; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Study Director, MD

CONTACT

6178580041; sky0515trials@skyhawktx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double-blind placebo-controlled dose ranging

Study Record Dates

• First Submitted: January 13, 2026
• First Posted: January 30, 2026
• Study Start: January 6, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): August 1, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GE (2); BR (1); AR (1)