## Protocol Section
### Identification Module
**NCT ID:** NCT05463679

**Acronym:** PREVEnt

**Brief Title:** 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)

#### Organization Study ID Info
**ID:** AR101-PREVEnt
#### Organization
**Class:** INDUSTRY
**Full Name:** Aytu BioPharma, Inc.
### Status Module
#### Completion Date
**Date:** 2027-03

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-03-08

**Type:** ACTUAL

**Last Update Submit Date:** 2024-03-06

**Overall Status:** SUSPENDED

#### Primary Completion Date
**Date:** 2025-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2025-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-03

#### Study First Post Date
**Date:** 2022-07-19
**Type:** ACTUAL
**Study First Submit Date:** 2022-04-06
**Study First Submit QC Date:** 2022-07-14
**Why Stopped:** Indefinite hold by company
### Sponsor Collaborators Module

#### Collaborators

**Class:** INDUSTRY

**Name:** Parexel

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Aytu BioPharma, Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

**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.

### Conditions Module

**Conditions:**

- Vascular Ehlers-Danlos Syndrome

### Design Module

#### Design Info

**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.

##### Masking Info

**Masking:** TRIPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 260

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Receive 500 mg enzastaurin QD plus background standard of care.

**Intervention Names:**

- Drug: Enzastaurin

**Label:** Enzastaurin 500 mg QD

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** Matching placebo QD plus background standard of care.

**Intervention Names:**

- Drug: Placebo

**Label:** Placebo QD

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Enzastaurin 500 mg QD

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

**Name:** Enzastaurin

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Placebo QD

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

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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

**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.

**Time Frame:** 30 months

#### Secondary Outcomes

**Description:** 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.

**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.

**Time Frame:** 30 months

**Description:** Discontinuation or withdrawal from the study

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

**Time Frame:** 30 months

### Eligibility Module

**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.

**Maximum Age:** 60 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Englewood

**Country:** United States

**Facility:** Aytu BioPharma

**State:** Colorado

**Zip:** 80112

#### Overall Officials

**Official 1:**

**Affiliation:** University of Washington

**Name:** Sherene Shalhub, M.D., M.P.H.

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Texas Children's Hospital and Baylor College of Medicine

**Name:** Shaine Morris, M.D.,M.P.H.

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### 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.

**PMID:** 31639107

#### See Also Links

**Label:** 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.

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

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004194

- Term: Disease

- ID: D000010335

- Term: Pathologic Processes

- ID: D000020141

- Term: Hemostatic Disorders

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000006474

- Term: Hemorrhagic Disorders

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000012868

- Term: Skin Abnormalities

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000012873

- Term: Skin Diseases, Genetic

- ID: D000030342

- Term: Genetic Diseases, Inborn

- ID: D000003095

- Term: Collagen Diseases

- ID: D000003240

- Term: Connective Tissue Diseases

- ID: D000012871

- Term: Skin Diseases

- ID: D000000784

- Term: Aortic Dissection

- ID: D000094665

- Term: Dissection, Blood Vessel

- ID: D000000783

- Term: Aneurysm

### Condition Browse Module - Browse Branches

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16355

- Name: Syndrome

- Relevance: HIGH

- As Found: Syndrome

- ID: M7704

- Name: Ehlers-Danlos Syndrome

- Relevance: HIGH

- As Found: Ehlers-Danlos Syndrome

- ID: M3069

- Name: Ehlers-Danlos Syndrome, Type IV

- Relevance: HIGH

- As Found: Vascular Ehlers-Danlos Syndrome

- ID: M21977

- Name: Hemostatic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5059

- Name: Blood Coagulation Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9560

- Name: Hemorrhagic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15672

- Name: Skin Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15676

- Name: Skin Diseases, Genetic

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: M15045

- Name: Rheumatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6323

- Name: Collagen Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6464

- Name: Connective Tissue Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4114

- Name: Aortic Dissection

- Relevance: LOW

- As Found: Unknown

- ID: M3081

- Name: Dissection, Blood Vessel

- Relevance: LOW

- As Found: Unknown

- ID: M4113

- Name: Aneurysm

- Relevance: LOW

- As Found: Unknown

- ID: T2043

- Name: Ehlers-Danlos Syndromes

- Relevance: HIGH

- As Found: Ehlers-Danlos Syndrome

- ID: T5841

- Name: Vascular Ehlers-Danlos Syndrome

- Relevance: HIGH

- As Found: Vascular Ehlers-Danlos Syndrome

### Condition Browse Module - Meshes

- ID: D000004535

- Term: Ehlers-Danlos Syndrome

- ID: D000094623

- Term: Ehlers-Danlos Syndrome, Type IV

- ID: D000013577

- Term: Syndrome

### Misc Info Module

- Version Holder: 2024-05-24
