SKY-0515-001 parts A and B

13 evidence topics · 5 sources

Objective

Primary objectives

“To investigate the safety and tolerability of a single oral dose administration of SKY-0515 in healthy adult participants” (opens the source at this quote in a new tab)
“To investigate the safety and tolerability of multiple oral dose administrations of SKY-0515 in healthy adult participants.” (opens the source at this quote in a new tab)

Location and study date

Site and enrollment start

Item	Registry record
Recruitment hospital	“CMAX Clinical Research Pty Ltd - Adelaide”
Date of first participant enrolment (actual)	“20/11/2023”

Study design

Randomized, double-blind, placebo-controlled SAD and MAD

“This is a randomised, double-blind, placebo-controlled, single ascending dose (SAD), multiple ascending dose (MAD) multi-cohort study.” (opens the source at this quote in a new tab)

Food-effect cohort

“Cohort 6 (food effect) a fed or fasted, 2-period, open label, crossover design, 8 healthy adult participants will be randomised to one of 2 treatment sequences (AB/BA)” (opens the source at this quote in a new tab)

CSF sampling cohorts

“Cerebrospinal Fluid samples will also be taken from participants enrolled in Cohorts 9 and 10.” (opens the source at this quote in a new tab)

Eligibility criteria

Key inclusion criteria

“Healthy male or female, aged between 18 and 70 years, inclusive at screening.” (opens the source at this quote in a new tab)
“Body mass index (BMI) of 18 to 35 kg/m2, inclusive, with body weight greater than or equal to 50.0 kg and < 130.0 kg.” (opens the source at this quote in a new tab)

Treatment

Dose ranges

“In Part A, five cohorts of participants were dosed with escalating single doses of SKY-0515 ranging from 1mg to 16mg or placebo.” (opens the source at this quote in a new tab)
“In Part B, three cohorts of participants were randomized to receive multiple ascending doses of SKY-0515 ranging from 1mg to 9mg or placebo administered daily from days 1 to 14 (inclusive).” (opens the source at this quote in a new tab)

Placebo

“Placebo drug product is microcrystalline cellulose capsule, packaged and encapsulated to look identical in appearance to SKY-0515.” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using safety and tolerability as the primary endpoint

Not applicable.

Statistical analysis description

Number of participants (Planned and analyzed)

Planned sample sizes

“The sample sizes of 40 participants (30 receiving SKY-0515 and 10 placebo) in Part A (Cohorts 1 to 5), 8 participants (all receiving SKY-0515) in Part A (Cohort 6), 32 participants (24 receiving SKY-0515 and 8 placebo) in Part B are considered adequate to meet the objectives of the study.” (opens the source at this quote in a new tab)

Enrolled and analyzed participants

No evidence found.

Description of analysis sets

Sample size justification

“This is a FIH study for SKY-0515. As such, no formal sample size calculations have been performed.” (opens the source at this quote in a new tab)

Results

Participant disposition

No evidence found.

Baseline characteristics

No evidence found.

Efficacy results

Pharmacodynamic results: blood HTT mRNA

“SKY-0515 demonstrated an average HTT mRNA reduction of 72% at a daily oral dose of 9mg and was generally well tolerated at all doses tested.” (opens the source at this quote in a new tab)

“SKY-0515 produced dose-dependent reductions in HTT mRNA, with maximum decreases of 67% after a single 16 mg dose and 72% after 14 days of 9 mg daily dosing.” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

Not applicable.

Safety results

Severe and serious adverse events and TEAE severity

“In healthy participants (SKY-0515-001 Parts A and B), no severe or serious adverse events were observed at single doses up to 16 mg and multiple doses up to 9 mg/day over 14 days; all treatment-emergent adverse events were mild or moderate, the most common being headache.” (opens the source at this quote in a new tab)

Adverse event incidence by cohort

No evidence found.

Study limitations

Summary

Parts A and B were designed for up to 80 healthy adults (40 in single ascending dose cohorts, 8 in a food-effect cohort, and 32 in multiple ascending dose cohorts) with no formal sample size calculation. Multiple dosing lasted 14 days. Only topline HTT mRNA reductions and a summary safety statement have been disclosed; enrolled numbers, adverse event incidence, half-life, food-effect, and CSF results from this part have not been published.