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

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

Overview

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 study is a randomized, double-blind, placebo-controlled trial conducted across multiple sites. This clinical trial aims to evaluate the safety, pharmacodynamics, and efficacy of SKY-0515, a novel, orally administered small molecule. Huntington's Disease (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, 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. 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). Safety and efficacy will be evaluated through blood tests, imaging (MRI), and clinical assessments, including the Unified Huntington's Disease Rating Scale (UHDRS).

Interventions

• Drug SKY-0515
  Type: Small molecule Dosage Level(s): Low, mid, high Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 18 months Use: Experimental
• Drug SKY-0515 Placebo
  Route of Administration: Oral Dosage Frequency: Once daily Blinded Treatment Duration: 18 months Use: Experimental

Primary outcome measures

• Change From Baseline in the Z-score from the Composite Unified Huntington's Disease Rating Scale (cUHDRS) [Time frame: 72 weeks]

Secondary outcome measures (5)

• Change from Baseline in Total Motor Score (TMS) [Time frame: 72 weeks]
• Change from Baseline in Total Functional Capacity (TFC) [Time frame: 72 weeks]
• Change from Baseline in Independence Scale Score (IS) [Time frame: 72 weeks]
• Change from Baseline in Symbol Digit Modalities Test (SDMT) [Time frame: 72 weeks]
• Change from Baseline in the Stroop Color and Word Test (SCWT) [Time frame: 72 weeks]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Brazil · 9 centers

• Centro de Pesquisas Clínicas do Hospital das Clínicas da Universidade Federal de Minas Ger — Belo Horizonte
• Hospital Angelina Caron — Campina Grande do Sul
• PUCPR - Centro de Pesquisa da Pontifícia Universidade Católica do Paraná — Curitiba
• Instituto de Neurologia de Curitiba — Curitiba
• Hospital Universitario Pedro Ernesto (HUPE) — Rio de Janeiro
• Hospital Universitário Onofre Lopes (HUOL) — Natal
• Faculdade de Medicina de Ribeirão Preto - FMRP — Ribeirão Preto
• PSEG Centro de Pesquisa Clinica — São Paulo
• … and 1 more center

Argentina · 6 centers

• IADIN (Instituto Argentino de Investigación Neurológica) — Buenos Aires
• Buenos Aires British Hospital — CABA
• Instituto Argentino de Investigación Neurológica — CABA
• CINME Centro de Investigaciones Metabólicas — CABA
• Sanatorio Mater Dei — CABA
• Fundación Scherbovsky — Mendoza

Georgia · 2 centers

• Pineo Medical Ecosystem — Tbilisi
• Simon Khechinashvili University Hospital — Tbilisi

Canada · 1 center

• North York General Hospital — Toronto

Chile · 1 center

• CETRAM (Centro de Trastornos del Movimiento) — Santiago

Identifiers

NCT: NCT07378644 · SKY-0515-004-WW

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗