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

NCT06873334 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: SKY-0515-004-ANZ
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 12

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; Huntingtons Disease

Keywords

Sky-0515; Skyhawk; Mutant Huntington protein; HTT; mRNA; Huntington Disease; Splicing; Huntingtons Disease; Neurodegenerative

Outcome Measures

Primary Outcomes (3)

• Changes in blood mHTT protein levels

  12 months

• Changes in brain volume measured through MRI

  12 months

• Changes in UHDRS

  12 months

Study Arms (4)

1 (Active)

ACTIVE COMPARATOR

Dosage Level(s): Low dose once daily oral

Drug: SKY-0515

2 (Active)

ACTIVE COMPARATOR

Dosage Level(s): Mid dose once daily oral

Drug: SKY-0515

3 (Active)

ACTIVE COMPARATOR

Dosage Level(s): High dose once daily oral

Drug: SKY-0515

4 (Control)

PLACEBO COMPARATOR

Matching placebo once daily oral

Drug: SKY-0515 Placebo

Interventions

SKY-0515 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.

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

SKY-0515 Placebo 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

4 (Control)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Skyhawk Therapeutics, Inc.: lead

Study Sites (12)

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

The University of Queensland

Herston, Queensland, 4006, Australia

Location

Flinders Medical Centre

Adelaide, South Australia, 5042, Australia

Location

Launceston General Hospital

Launceston, Tasmania, 7250, Australia

Location

Calvary Health Care Bethlehem

Caulfield South, Victoria, 3162, Australia

Location

The Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

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

Nedlands, Western Australia, 6009, Australia

Location

Huntington's Disease Association

Auckland, 0604, New Zealand

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Christchurch Neurology Trials Limited

Christchurch, 8011, New Zealand

Location

Wellington Hospital

Wellington, 6021, New Zealand

Location

Related Links

• Skyhawk Therapeutics Website

MeSH Terms

Conditions

Huntington Disease; Chorea

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; 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; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Masoud Mokhtarani, MD

  Skyhawk Therapeutics, Inc.

  STUDY DIRECTOR

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: March 6, 2025
• First Posted: March 12, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (4); AU (8)