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

Phase 3

Recruiting

• Conditions: Vascular Ehlers-Danlos Syndrome
• Interventions: Drug: ACER-002 (celiprolol) 200 mg BID; Drug: Placebo BID

• Registration Number: NCT05432466
• Lead Sponsor: Acer Therapeutics Inc.

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.

Study Timeline

• Study First Submitted: 2022-06-21
• Study First Submitted QC: 2022-06-21
• Study First Posted: 2022-06-27
• Study Start: 2022-11-07
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-03
• Last Update Posted: 2024-06-04
• Primary Completion: 2029-03-01
• Study Completion: 2029-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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 prior to randomization.

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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 prior to randomization.
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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ACER-002 (celiprolol) 200 mg BID	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
Placebo BID	Placebo BID	Placebo twice daily (BID) Placebo given orally to mimic ACER-002 (celiprolol) administration

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	Over the double-blind period (estimated to be 40 months)	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)	Over the double-blind period (estimated to be 40 months)	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	Over the double-blind period (estimated to be 40 months)
Number and percentage of patient discontinuations	Over the double-blind period (estimated to be 40 months)	Discontinuation or withdrawal from the study

Trial Locations

Locations (1)

Science 37; 🇺🇸 Culver City, California, United States