Title
Investigate Efficacy, Safety, and Pharmacokinetics of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome.
A Multicenter, Randomized, Double-blind, Placebo-controlled Study of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome (vEDS) Confirmed With COL3A1 Mutations, Followed by an Open Label Extension (OLE)
Phase
Phase 3Lead Sponsor
AYTU BioScienceStudy Type
InterventionalStatus
SuspendedIndication/Condition
Vascular Ehlers-Danlos SyndromeIntervention/Treatment
Enzastaurin ...Study Participants
260The purpose of this study is to investigate the efficacy of enzastaurin compared to placebo in preventing arterial events (rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm, fatal or not) leading to intervention or mortality attributable to an arterial event in patients with vEDS confirmed with pathogenic heterozygous COL3A1 gene mutations predicted to derive a mutant protein.
The primary efficacy endpoint of this study will be defined as the time to intervention for an arterial event (rupture, dissection, pseudoaneurysm, carotid-cavernous sinus fistula, or aneurysm, fatal or not) or mortality attributable to an arterial event, as adjudicated by an Event Committee, and will be analyzed for difference of active vs. placebo treatments on top of background standard of care, using survival statistical analysis. Furthermore, secondary endpoints will include the rate of intestinal rupture, pneumothorax, and retinal detachment, as adjudicated by an Event Committee, safety and tolerability, as well as hospitalizations and Health Related Quality of Life (HQRL) measures.
500 mg QD orally in the form of four 125 mg tablets with background standard of care
Placebo to match enzastaurin 500 mg QD orally in the form of four 125 mg tablets with background standard of care
Receive 500 mg enzastaurin QD plus background standard of care.
Inclusion Criteria: Subjects aged 18 - 60 years old at time of initial screening. Adolescent subjects aged 12 - 17 years old, may be considered to enroll later in the clinical trial pending interim analysis. Diagnosis for VEDS (vascular Ehlers Danlos Syndrome), with a confirmed and documented COL3A1 genetic variant. Subject should be stable, having no VEDS-related vascular events within the past 3 months prior to enrollment. Confirmed use of contraception for both male and female participants. Exclusion Criteria: Inability to swallow or receive intact tablets. Currently being treated with CYP3A4 inhibitors within 4 weeks prior to enrollment. Known allergy or hypersensitivity to enzastaurin. Patient currently pregnant or breast feeding. Other criteria will be reviewed at the first study visit to determine if you are able to participate in the study.
