Vascular Ehlers-Danlos SyndromePhase 3PREVEntNCT05463679
Investigate Efficacy, Safety, and Pharmacokinetics of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome.
A Phase 3 study testing Enzastaurin in people with Vascular Ehlers-Danlos Syndrome, run by Aytu BioPharma, Inc. at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Vascular Ehlers-Danlos Syndrome
- What is being tested?
- Enzastaurin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 260 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2025to Mar 2027
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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)
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.
Read the 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
- Vascular Ehlers-Danlos Syndrome
- Being tested
- Enzastaurin, Placebo
- Medical subject headings
- Ehlers-Danlos Syndrome, Type IV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnzastaurinDrug
500 mg QD orally in the form of four 125 mg tablets with background standard of care
PlaceboDrug
Placebo to match enzastaurin 500 mg QD orally in the form of four 125 mg tablets with background standard of care
| Study group | Role | What they receive |
|---|---|---|
| Enzastaurin 500 mg QD | Active comparator | Receive 500 mg enzastaurin QD plus background standard of care. Receives: Drug: Enzastaurin |
| Placebo QD | Placebo comparator | Matching placebo QD plus background standard of care. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
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.
Measured: 30 months
Number of and proportion of patients who discontinue study drug due to adverse events
Discontinuation or withdrawal from the study
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2022
- Study startJan 2025 (estimated)
- Primary completionJun 2025 (estimated)
- Study completionMar 2027 (estimated)
Why it stopped: Indefinite hold by company
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Vascular Ehlers-Danlos SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aytu BioPharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Sherene Shalhub, M.D., M.P.H., Principal investigator, University of WashingtonShaine Morris, M.D.,M.P.H., Principal investigator, Texas Children's Hospital and Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05463679
- Sponsor's protocol ID
- AR101-PREVEnt
- Acronym
- PREVEnt
- Status last verified
- Mar 2024
- First submitted
- 6 Apr 2022
- Last updated
- 8 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31639107
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05463679
- Acronym / sponsor ID
- PREVEnt / AR101-PREVEnt
- Conditions
- Vascular Ehlers-Danlos Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Indefinite hold by company
- Enrolment
- 260 participants (estimated)
- Lead sponsor
- Aytu BioPharma, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- Jan 2025 (estimated)
- Primary completion
- Jun 2025 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 19 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Enzastaurin 500 mg QD | Active comparator | Drug: EnzastaurinReceive 500 mg enzastaurin QD plus background standard of care. |
| Placebo QD | Placebo comparator | Drug: PlaceboMatching placebo QD plus background standard of care. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enzastaurin500 mg QD orally in the form of four 125 mg tablets with background standard of care | Drug | Enzastaurin 500 mg QD |
| PlaceboPlacebo to match enzastaurin 500 mg QD orally in the form of four 125 mg tablets with background standard of care | Drug | Placebo QD |
Primary outcome
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
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
2 secondary outcomes
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
Number of and proportion of patients who discontinue study drug due to adverse events
Time frame: 30 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2024.
- Background: PubMed 31639107Bowen 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.
- 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.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sherene Shalhub, M.D., M.P.H. principal investigator
University of Washington
Shaine Morris, M.D.,M.P.H. principal investigator
Texas Children's Hospital and Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enzastaurin in people with Vascular Ehlers-Danlos Syndrome, run by Aytu BioPharma, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05463679, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.