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

Primary Purpose

Vascular Ehlers-Danlos Syndrome

Status

Suspended

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Enzastaurin

Placebo

About this trial

This is an interventional prevention trial for Vascular Ehlers-Danlos Syndrome

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Aytu BioPharma

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Enzastaurin 500 mg QD

Placebo QD

Arm Description

Receive 500 mg enzastaurin QD plus background standard of care.

Matching placebo QD plus background standard of care.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

An Adverse Event (AE) is defined as any untoward medical occurrence associated with the use of the investigational product in humans, whether or not considered related to investigational product. An AE can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with any use of the investigational product, without any judgment about causality and irrespective of route of administration, formulation, or dose, including an overdose.

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

Discontinuation or withdrawal from the study

Full Information

NCT ID

NCT05463679

First Posted

April 6, 2022

Last Updated

October 13, 2022

Sponsor

Aytu BioPharma, Inc.

Collaborators

Parexel

1. Study Identification

Unique Protocol Identification Number

NCT05463679

Brief Title

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

Acronym

PREVEnt

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

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Suspended

Why Stopped

Indefinite hold by company

Study Start Date

January 2024 (Anticipated)

Primary Completion Date

June 2025 (Anticipated)

Study Completion Date

March 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Aytu BioPharma, Inc.

Collaborators

Parexel

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Vascular Ehlers-Danlos Syndrome

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

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.

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

260 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Enzastaurin 500 mg QD

Arm Type

Active Comparator

Arm Description

Receive 500 mg enzastaurin QD plus background standard of care.

Arm Title

Placebo QD

Arm Type

Placebo Comparator

Arm Description

Matching placebo QD plus background standard of care.

Intervention Type

Drug

Intervention Name(s)

Enzastaurin

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

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.

Description

Time Frame

30 months

Secondary Outcome Measure Information:

Title

Description

Time Frame

30 months

Title

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

Description

Discontinuation or withdrawal from the study

Time Frame

30 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sherene Shalhub, M.D., M.P.H.

Organizational Affiliation

University of Washington

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Shaine Morris, M.D.,M.P.H.

Organizational Affiliation

Texas Children's Hospital and Baylor College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Aytu BioPharma

City

Englewood

State/Province

Colorado

ZIP/Postal Code

80112

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

31639107

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.

Results Reference

background

Links:

URL

https://www.clinicaltrials.gov/ct2/show/NCT00332202

Description

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.

Learn more about this trial

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

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