Clinical Trial to Compare the Efficacy of Celiprolol to Placebo in Patients With Vascular Ehlers-Danlos Syndrome - Clinical Trial for Vascular Ehlers-Danlos Syndrome | NCT05432466

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Primary Purpose

Status

Recruiting

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

ACER-002 (celiprolol) 200 mg BID

Placebo BID

About this trial

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

Eligibility Criteria

15 Years - 64 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Willingness to obtain magnetic resonance angiogram (MRA) image at local imaging facility.
A genetic test confirming the presence of a pathogenic COL3A1 variant (classified as likely pathogenic or pathogenic according to ACMG/AMP Guidelines.
Patients must be ≥ 15 years of age at the time of randomization.
Able and willing to discontinue use of β-blockers 28 days prior to enrollment .

Exclusion Criteria:

Lack of a COL3A1-positive test at screening (e.g., COL3A1 benign, likely benign, variant of unknown significance [VUS] or no variant) or presence of a COL3A1 variant but demonstration of a COL3A1 variant reported to be a haploinsufficiency variant.
Arterial rupture or dissection, uterine rupture, and/or intestinal rupture within 6 months prior to Screening.
Patients unable to discontinue β-blocker treatment within 28 days of enrollment.
Unable or unwilling to complete the study procedures.
Breastfeeding, pregnancy, or planned pregnancy during the trial.
Any medical condition that in the opinion of the Investigator may pose a safety risk to the patient in this study, which may confound efficacy or safety assessment, or may interfere with study participation.
Use of any prohibited medications

Sites / Locations

Science 37Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

ACER-002 (celiprolol) 200 mg BID

Placebo BID

Arm Description

ACER-002 200 mg twice daily (BID) (after titration): 200 mg morning and 200 mg evening: 400 mg total daily dose Titration: Day 1 to Month 1 - 100 mg once daily (QD) evening: 100 mg total daily dose Month 2 to Month 3 - 100 mg morning and 100 mg evening: 200 mg total daily dose Month 3 to Month 4 - 100 mg morning and 200 mg evening: 300 mg total daily dose Month 4 to End of Treatment Period (BID) - 200 mg morning and 200 mg evening: 400 mg total daily dose

Placebo twice daily (BID) Placebo given orally to mimic ACER-002 (celiprolol) administration

Outcomes

Primary Outcome Measures

Time to first occurrence of a vEDS-related clinical event requiring medical attention: Fatal/nonfatal cardiac or arterial events [including dissection or rupture], uterine rupture, intestinal rupture, and/or unexplained sudden death

Secondary Outcome Measures

Number and proportion of patients reporting a vEDS related clinical event requiring medical attention: Fatal/nonfatal cardiac or arterial events [including dissection or rupture], uterine rupture, intestinal rupture, and/or unexplained sudden death

Number and percentage of patients with adverse events

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 and percentage of Serious Adverse Events (SAE)

An AE is considered "serious" if, in the view of either the investigator or Acer, it results in any of the following outcomes: Death, Is immediately life threatening; Requires in-patient hospitalization or prolongation of existing hospitalization; Results in persistent or significant disability or incapacity; Results in a congenital abnormality or birth defect; Is an important medical event that may jeopardize the subject or may require medical intervention to prevent one of the outcomes listed above.

Number and percentage of patient deaths

Number and percentage of patient discontinuations

Discontinuation or withdrawal from the study

Full Information

NCT ID

NCT05432466

First Posted

June 21, 2022

Last Updated

November 8, 2022

Sponsor

Acer Therapeutics Inc.

1. Study Identification

Unique Protocol Identification Number

NCT05432466

Brief Title

Clinical Trial to Compare the Efficacy of Celiprolol to Placebo in Patients With Vascular Ehlers-Danlos Syndrome

Acronym

DiSCOVER

Official Title

A Phase 3 Randomized, Double-Blind, Decentralized Clinical Trial to Compare the Efficacy of Celiprolol to Placebo in the Treatment of Patients With COL3A1-Positive Vascular Ehlers-Danlos Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Recruiting

Study Start Date

November 7, 2022 (Actual)

Primary Completion Date

October 30, 2025 (Anticipated)

Study Completion Date

November 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Acer Therapeutics Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a prospective, Phase 3, randomized, double-blind, placebo-controlled efficacy study to evaluate celiprolol in patients genetically confirmed as COL3A1-positive vEDS using a decentralized clinical trial design.

Detailed Description

This is a prospective, Phase 3, randomized, double-blind, placebo-controlled efficacy study to evaluate celiprolol in patients genetically confirmed as COL3A1-positive vEDS using a decentralized clinical trial design. The double-blind portion of this study is intended to end if statistical significance is reached at the interim analysis (accrual of 28 vEDS-related events requiring medical attention; estimated to take 24 months) or after accrual of 46 vEDS related clinical events requiring medical attention (estimated to take 40 months). A total of approximately 150 patients who meet all the inclusion and none of the exclusion criteria will be enrolled and randomized 2:1 to receive either celiprolol or placebo, respectively. Following the double-blind treatment period or occurrence of vEDS-related clinical event, patients have the option to participate in an open label extension period.

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

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

This is a prospective, Phase 3, randomized, double-blind, placebo-controlled efficacy study to evaluate celiprolol in patients genetically confirmed as COL3A1-positive vEDS using a decentralized clinical trial design. The double-blind portion of this study is intended to end at Month 40 assuming that at least 46 vEDS-related clinical events have occurred. If the number of vEDS-related events is fewer than 46 at Month 40, the study will continue until the required number of events have occurred prior to ending the double-blind portion of the study. Following the double-blind treatment period or occurrence of a vEDS-related clinical event, patients have the option to participate in an OLE period. A total of approximately 150 patients who meet all the inclusion and none of the exclusion criteria will be enrolled and randomized 2:1 to receive either celiprolol or placebo, respectively. An approximately 40-month treatment period followed by an optional open-label extension study.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

The patient, the Investigator, and other members of the staff involved with the study will remain blinded to the two study treatments (celiprolol and placebo).

Allocation

Randomized

Enrollment

150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

ACER-002 (celiprolol) 200 mg BID

Arm Type

Experimental

Arm Description

ACER-002 200 mg twice daily (BID) (after titration): 200 mg morning and 200 mg evening: 400 mg total daily dose Titration: Day 1 to Month 1 - 100 mg once daily (QD) evening: 100 mg total daily dose Month 2 to Month 3 - 100 mg morning and 100 mg evening: 200 mg total daily dose Month 3 to Month 4 - 100 mg morning and 200 mg evening: 300 mg total daily dose Month 4 to End of Treatment Period (BID) - 200 mg morning and 200 mg evening: 400 mg total daily dose

Arm Title

Placebo BID

Arm Type

Experimental

Arm Description

Placebo twice daily (BID) Placebo given orally to mimic ACER-002 (celiprolol) administration

Intervention Type

Drug

Intervention Name(s)

ACER-002 (celiprolol) 200 mg BID

Other Intervention Name(s)

ACER-002, celiprolol

Intervention Description

ACER-002 (celiprolol) 200 mg BID

Intervention Type

Drug

Intervention Name(s)

Placebo BID

Other Intervention Name(s)

placebo

Intervention Description

placebo for ACER-002

Primary Outcome Measure Information:

Title

Time to first occurrence of a vEDS-related clinical event requiring medical attention: Fatal/nonfatal cardiac or arterial events [including dissection or rupture], uterine rupture, intestinal rupture, and/or unexplained sudden death

Time Frame