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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Vascular Ehlers-Danlos Syndrome
• Intervention / Treatment: Drug: ACER-002 (celiprolol) 200 mg BID; Drug: Placebo BID

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sheila Woodhouse, Ph.D.; Phone Number: 984-377-3737; Email: sheila.woodhouse@science37.com
• Study Contact Backup: Name: Jonathan Cotliar, Ph.D.; Phone Number: 984-377-3737; Email: jonathan@science37.com

Study Locations

• United States
  • California
    • Culver City, California, United States, 90230
      • Recruiting
      • Science 37
      • Contact: Sheila Woodhouse, MD; Phone Number: 984-377-3737; Email: sheila.woodhouse@science37.com
      • Contact: Johnathan Cotliar, MD; Phone Number: 984-377-3737; Email: jonathan@science37.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 64 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. 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.
2. Arterial rupture or dissection, uterine rupture, and/or intestinal rupture within 6 months prior to Screening.
3. Patients unable to discontinue β-blocker treatment within 28 days of enrollment.
4. Unable or unwilling to complete the study procedures.
5. Breastfeeding, pregnancy, or planned pregnancy during the trial.
6. 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.
7. Use of any prohibited medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ACER-002 (celiprolol) 200 mg BID; 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	Drug: ACER-002 (celiprolol) 200 mg BID; ACER-002 (celiprolol) 200 mg BID; Other Names: ACER-002; celiprolol
Experimental: Placebo BID; Placebo twice daily (BID) Placebo given orally to mimic ACER-002 (celiprolol) administration	Drug: Placebo BID; placebo for ACER-002; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Over the double-blind period (estimated to be 40 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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		Over the double-blind period (estimated to be 40 months)
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.	Over the double-blind period (estimated to be 40 months)
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.	Over the double-blind period (estimated to be 40 months)
Number and percentage of patient deaths		Over the double-blind period (estimated to be 40 months)
Number and percentage of patient discontinuations	Discontinuation or withdrawal from the study	Over the double-blind period (estimated to be 40 months)

Collaborators and Investigators

• Sponsor: Acer Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2022
• Primary Completion (Estimated): October 30, 2025
• Study Completion (Estimated): November 30, 2025

Study Registration Dates

• First Submitted: June 21, 2022
• First Submitted That Met QC Criteria: June 21, 2022
• First Posted (Actual): June 27, 2022

Study Record Updates

• Last Update Posted (Estimated): December 14, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Aneurysm; Collagen Diseases; Dissection, Blood Vessel; Aortic Dissection; Syndrome; Ehlers-Danlos Syndrome; Ehlers-Danlos Syndrome, Type IV; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympathomimetics; Adrenergic beta-1 Receptor Antagonists; Celiprolol
• Other Study ID Numbers: ACER-002-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No