Huntington DiseasePhase 2/3Falcon-HDNCT06873334
Study of SKY-0515 for Safety, Efficacy, and Pharmacodynamics in Participants With Huntington's Disease
A Phase 2/3 study testing SKY-0515 in people with Huntington Disease and Huntingtons Disease, run by Skyhawk Therapeutics, Inc. at 12 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 years and older
- Conditions the study is for
- Huntington Disease, Huntingtons Disease
- What is being tested?
- SKY-0515
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 27 May 2025to Dec 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
Australia8 sites
Flinders Medical Centre
Adelaide, South Australia, 5042
Calvary Health Care Bethlehem
Caulfield South, Victoria, 3162
The University of Queensland
Herston, Queensland, 4006
Launceston General Hospital
Launceston, Tasmania, 7250
The Perron Institute for Neurology and Translational Science (Perron Institute)
Nedlands, Western Australia, 6009
John Hunter Hospital
New Lambton Heights, New South Wales, 2305
The Royal Melbourne Hospital
Parkville, Victoria, 3050
Westmead Hospital
Westmead, New South Wales, 2145
New Zealand4 sites
Huntington's Disease Association
Auckland, 0604
Auckland City Hospital
Auckland, 1023
Christchurch Neurology Trials Limited
Christchurch, 8011
Wellington Hospital
Wellington, 6021
About this study
Official title: 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.
Read the detailed description
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:
- Screening Period (up to 4 weeks): Participants will undergo eligibility assessments.
- 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).
- 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
- Huntington Disease, Huntingtons Disease
- Being tested
- SKY-0515, SKY-0515 Placebo
- Keywords
- Sky-0515, Skyhawk, Mutant Huntington protein, HTT, mRNA, Huntington Disease, Splicing, Huntingtons Disease, Neurodegenerative
- Medical subject headings
- Huntington Disease, Chorea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SKY-0515Drug
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.
SKY-0515 PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 1 (Active) | Active comparator | Dosage Level(s): Low dose once daily oral Receives: Drug: SKY-0515 |
| 2 (Active) | Active comparator | Dosage Level(s): Mid dose once daily oral Receives: Drug: SKY-0515 |
| 3 (Active) | Active comparator | Dosage Level(s): High dose once daily oral Receives: Drug: SKY-0515 |
| 4 (Control) | Placebo comparator | Matching placebo once daily oral Receives: Drug: SKY-0515 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in blood mHTT protein levels
Measured: 12 months
Changes in brain volume measured through MRI
Measured: 12 months
Changes in UHDRS
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2025
- Study start27 May 2025
- Primary completionMay 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Huntington DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind placebo-controlled dose ranging.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Skyhawk Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Masoud Mokhtarani, MD, Study director, Skyhawk Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06873334
- Sponsor's protocol ID
- SKY-0515-004-ANZ
- Acronym
- Falcon-HD
- Status last verified
- Apr 2026
- First submitted
- 6 Mar 2025
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06873334
- Acronym / sponsor ID
- Falcon-HD / SKY-0515-004-ANZ
- Conditions
- Huntington Disease, Huntingtons Disease
- Keywords
- Sky-0515, Skyhawk, Mutant Huntington protein, HTT, mRNA, Huntington Disease, Splicing, Huntingtons Disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Skyhawk Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 May 2025 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 12 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- Screening Period (up to 4 weeks): Participants will undergo eligibility assessments.
- 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).
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Double-blind placebo-controlled dose ranging.
| Arm | Type | Receives |
|---|---|---|
| 1 (Active) | Active comparator | Drug: SKY-0515Dosage Level(s): Low dose once daily oral |
| 2 (Active) | Active comparator | Drug: SKY-0515Dosage Level(s): Mid dose once daily oral |
| 3 (Active) | Active comparator | Drug: SKY-0515Dosage Level(s): High dose once daily oral |
| 4 (Control) | Placebo comparator | Drug: SKY-0515 PlaceboMatching placebo once daily oral |
Who may qualify
- Ages
- 25 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SKY-0515Study 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. | Drug | 1 (Active), 2 (Active), 3 (Active) |
| SKY-0515 PlaceboRoute 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 | Drug | 4 (Control) |
Primary outcome
Changes in blood mHTT protein levels
Time frame: 12 months
Changes in brain volume measured through MRI
Time frame: 12 months
Changes in UHDRS
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Skyhawk Therapeutics WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Masoud Mokhtarani, MD study director
Skyhawk Therapeutics, Inc.
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing SKY-0515 in people with Huntington Disease and Huntingtons Disease, run by Skyhawk Therapeutics, Inc. at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in blood mHTT protein levels (time frame: 12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.