Investigate Efficacy, Safety, and Pharmacokinetics of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome.

NCT05463679 | Suspended Phase 3 DMC FDA Drug

• 1 other identifier: AR101-PREVEnt
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

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.

Conditions

Vascular Ehlers-Danlos Syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  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 analyzed for difference in the time-to-composite-event of active vs. placebo treatments, using survival analysis until end of study

  30 months

Secondary Outcomes (2)

• 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.

  30 months

• Number of and proportion of patients who discontinue study drug due to adverse events

  30 months

Study Arms (2)

Enzastaurin 500 mg QD

ACTIVE COMPARATOR

Receive 500 mg enzastaurin QD plus background standard of care.

Drug: Enzastaurin

Placebo QD

PLACEBO COMPARATOR

Matching placebo QD plus background standard of care.

Drug: Placebo

Interventions

Enzastaurin DRUG

500 mg QD orally in the form of four 125 mg tablets with background standard of care

Enzastaurin 500 mg QD

Placebo DRUG

Placebo to match enzastaurin 500 mg QD orally in the form of four 125 mg tablets with background standard of care

Placebo QD

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aytu BioPharma, Inc.: lead
• Parexel: collaborator

Study Sites (1)

Aytu BioPharma

Englewood, Colorado, 80112, United States

Location

Related Publications (1)

• 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.

  PMID: 31639107 BACKGROUND

Related Links

• 2\. Bowen CJ et al. Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos Syndrome. J Clin Invest. 2020 Feb 3;130(2):686-698.

MeSH Terms

Conditions

Ehlers-Danlos Syndrome, Type IV

Interventions

enzastaurin

Condition Hierarchy (Ancestors)

Aortic Dissection; Dissection, Blood Vessel; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Ehlers-Danlos Syndrome; Hemostatic Disorders; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Skin Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Genetic Diseases, Inborn; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Sherene Shalhub, M.D., M.P.H.

  University of Washington

  PRINCIPAL INVESTIGATOR

• Shaine Morris, M.D.,M.P.H.

  Texas Children's Hospital and Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 6, 2022
• First Posted: July 19, 2022
• Study Start: January 1, 2025
• Primary Completion: June 1, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)