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

NCT ID: NCT06873334

Last Updated: 2026-02-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-05-27

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Huntington Disease Huntingtons Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Double-blind placebo-controlled dose ranging.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1 (Active)

Dosage Level(s): Low dose once daily oral

Group Type ACTIVE_COMPARATOR

SKY-0515

Intervention Type DRUG

Study Drug Name (INN): SKY-0515 Type: Drug (small molecule) Dosage Level(s): Low, mid, high Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 12 months

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 blinded 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.

2 (Active)

Dosage Level(s): Mid dose once daily oral

Group Type ACTIVE_COMPARATOR

SKY-0515

Intervention Type DRUG

Study Drug Name (INN): SKY-0515 Type: Drug (small molecule) Dosage Level(s): Low, mid, high Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 12 months

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 blinded 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.

3 (Active)

Dosage Level(s): High dose once daily oral

Group Type ACTIVE_COMPARATOR

SKY-0515

Intervention Type DRUG

Study Drug Name (INN): SKY-0515 Type: Drug (small molecule) Dosage Level(s): Low, mid, high Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 12 months

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 blinded 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.

4 (Control)

Matching placebo once daily oral

Group Type PLACEBO_COMPARATOR

SKY-0515 Placebo

Intervention Type DRUG

Route of Administration: Oral Dosage

Frequency: Once daily

Blinded Treatment Duration: 12 months

Use: Experimental

Sourcing: SKY-0515 placebo will be provided centrally by the Sponsor or subsidiary, or designee

Packaging and Labeling: Study drug will be provided in blinded 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

Interventions

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SKY-0515

Study Drug Name (INN): SKY-0515 Type: Drug (small molecule) Dosage Level(s): Low, mid, high Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 12 months

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 blinded 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.

Intervention Type DRUG

SKY-0515 Placebo

Route of Administration: Oral Dosage

Frequency: Once daily

Blinded Treatment Duration: 12 months

Use: Experimental

Sourcing: SKY-0515 placebo will be provided centrally by the Sponsor or subsidiary, or designee

Packaging and Labeling: Study drug will be provided in blinded 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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* You must be 25 years or older.
* You must have Huntington's Disease confirmed through genetic testing, with a specific 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 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.
* You must agree to sign a consent form and follow the study's rules and schedule.

Exclusion Criteria

* You have other serious health problems or brain/spinal issues that could interfere with the study or make procedures unsafe.
* You have a condition that interferes with protocol-specified assessments, like an implanted medical device or difficulty getting an MRI.
* You have cancer, except for some types of skin cancer, or a history of cancer in the last 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 (or longer for some drugs).
* You have had any kind of gene therapy.
* You have a history of suicidal thoughts, severe depression, or have attempted suicide 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.
Minimum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Skyhawk Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Masoud Mokhtarani, MD

Role: STUDY_DIRECTOR

Skyhawk Therapeutics, Inc.

Locations

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John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Site Status RECRUITING

Westmead Hospital

Westmead, New South Wales, Australia

Site Status RECRUITING

The University of Queensland

Herston, Queensland, Australia

Site Status RECRUITING

Flinders Medical Centre

Adelaide, South Australia, Australia

Site Status RECRUITING

Calvary Health Care Bethlehem

Caulfield South, Victoria, Australia

Site Status RECRUITING

The Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status RECRUITING

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

Nedlands, Western Australia, Australia

Site Status RECRUITING

Huntington's Disease Association

Auckland, , New Zealand

Site Status RECRUITING

Auckland City Hospital

Auckland, , New Zealand

Site Status RECRUITING

Christchurch Neurology Trials Limited

Christchurch, , New Zealand

Site Status RECRUITING

Wellington Hospital

Wellington, , New Zealand

Site Status RECRUITING

Countries

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Australia New Zealand

Central Contacts

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General Inquiries

Role: CONTACT

6178580041

Facility Contacts

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Gillian Harris

Role: primary

+61 2 49855284

Natalia Murray

Role: backup

02 4021 3484

Sarah Samperi

Role: primary

+61 2 8890 9146

Florence Chang

Role: backup

+61 2 8890 8908

Angela Schmidt

Role: primary

07 3346 5583

Simon Windsor

Role: primary

+61 403 109 641

Research Enquiries

Role: primary

+61 3 9834 9430

Yenni Lie

Role: backup

+61 3 9834 9000

Office For Research

Role: primary

0393428530

Melanie Clark

Role: primary

+61 8 6457 0200

Jo Dysart

Role: primary

+64 800 43 282

Principal Investigator

Role: backup

Hina Karim

Role: primary

+64 21 896 662

Laura Paermentier

Role: primary

+64 3378 662

Grace Hodgson

Role: primary

+64 04 806 0076

David Bourke

Role: backup

04 385 5999

Related Links

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https://www.skyhawktx.com/

Skyhawk Therapeutics Website

Other Identifiers

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SKY-0515-004-ANZ

Identifier Type: -

Identifier Source: org_study_id

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