SKY-0515 for adults 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

This trial will test whether the oral drug SKY-0515 can lower harmful huntingtin protein and improve symptoms in adults aged 25 and older with genetically confirmed Huntington's disease.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 25 Years and up
• Sex: All
• Sponsor: Skyhawk Therapeutics, Inc. (Industry-sponsored)
• Locations: 4 sites (Buenos Aires and 3 other locations)
• Trial ID: NCT07378644 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled, multi-site trial testing an oral small molecule, SKY-0515, across three dose levels versus placebo. SKY-0515 is designed to reduce both mutant and wild-type huntingtin (HTT) protein levels and to lower PMS1, a protein linked to somatic CAG repeat expansion that drives disease progression. Eligible participants are adults (25+) with genetically confirmed HD (CAG ≥ 40) who meet specified motor and functional thresholds and can undergo MRI and required safety monitoring. Safety, pharmacodynamic markers in blood, MRI measures, and clinical outcomes including the UHDRS will be used to compare the treatment arms to placebo.

Who should consider this trial

Good fit: Adults aged 25 or older with genetically confirmed Huntington's disease (CAG repeat ≥ 40) who meet the trial's motor and functional thresholds (TFC ≥ 10, TMS ≥ 6, IS ≥ 70) and can comply with imaging, blood tests, and contraception rules are ideal candidates.

Not a fit: People with more advanced disease below the functional/motor cutoffs, significant comorbidities, MRI contraindications, current pregnancy, or who cannot meet contraception requirements are unlikely to benefit or will be ineligible.

Why it matters

Potential benefit: If successful, SKY-0515 could lower disease-driving huntingtin levels and slow symptom progression or improve function for people with HD.

How similar studies have performed: Gene-silencing approaches (like antisense oligonucleotides) have shown reduction of mutant huntingtin protein in humans with mixed clinical effects, while an oral small-molecule approach targeting HTT and PMS1 is relatively novel and less tested in patients.

Eligibility criteria

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.

Where this trial is running

Buenos Aires and 3 other locations

• CINME Centro de Investigaciones Metabólicas — Buenos Aires, Argentina (Recruiting)
• PSEG Centro de Pesquisa Clinica — São Paulo, São Paulo, Brazil (Not_yet_recruiting)
• Pineo Medical Ecosystem — Tbilisi, Georgia (Recruiting)
• Simon Khechinashvili University Hospital — Tbilisi, Georgia (Recruiting)

Study contacts

• Study coordinator: Study Director, MD

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