Clinical trial NCT05463679: Investigate Efficacy, Safety, and Pharmacokinetics of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome.
Official title: 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)
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE3
Conditions: Vascular Ehlers-Danlos Syndrome
Lead sponsor: Aytu BioPharma, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2022-07-19
Enrollment: 260
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two-arm, multicenter, randomized, double-blind, placebo-controlled study in patients with vEDS receiving enzastaurin 500 mg once daily (QD) compared to placebo, in addition to background standard of care, followed by an OLE phase.

Approximately 260 patients with vEDS are planned to be randomized in a 1:1 ratio of enzastaurin or placebo. Patients will be enrolled in the study if they meet all eligibility criteria.
Primary purpose: PREVENTION

Brief summary: The 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Subjects aged 18 - 60 years old at time of initial screening.
2. Adolescent subjects aged 12 - 17 years old, may be considered to enroll later in the clinical trial pending interim analysis.
3. Diagnosis for VEDS (vascular Ehlers Danlos Syndrome), with a confirmed and documented COL3A1 genetic variant.
4. Subject should be stable, having no VEDS-related vascular events within the past 3 months prior to enrollment.
5. Confirmed use of contraception for both male and female participants.

Exclusion Criteria:

1. Inability to swallow or receive intact tablets.
2. Currently being treated with CYP3A4 inhibitors within 4 weeks prior to enrollment.
3. Known allergy or hypersensitivity to enzastaurin.
4. 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.

Primary outcomes:
measure: 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.
timeFrame: 30 months
Secondary outcomes:
measure: Number of and proportion of patients with adverse events, or with abnormal vital signs, physical examinations, ophthalmological examinations, clinical laboratory values, or electrocardiograms (ECGs) medical attention.
timeFrame: 30 months
measure: Number of and proportion of patients who discontinue study drug due to adverse events
timeFrame: 30 months
Other outcomes:
Locations:
city: Englewood
country: United States
facility: Aytu BioPharma
state: Colorado
Study officials:
affiliation: University of Washington
name: Sherene Shalhub, M.D., M.P.H.
role: PRINCIPAL_INVESTIGATOR
affiliation: Texas Children's Hospital and Baylor College of Medicine
name: Shaine Morris, M.D.,M.P.H.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bowen CJ, Calderon Giadrosic JF, Burger Z, Rykiel G, Davis EC, Helmers MR, Benke K, Gallo MacFarlane E, Dietz HC. Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome. J Clin Invest. 2020 Feb 3;130(2):686-698. doi: 10.1172/JCI130730.