Clinical Trial to Compare the Efficacy of Celiprolol to Placebo in Patients With 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.

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.

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 prior to randomization.

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 prior to randomization.
• 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