Clinical trial NCT05432466: Clinical Trial to Compare the Efficacy of Celiprolol to Placebo in Patients With Vascular Ehlers-Danlos Syndrome
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Vascular Ehlers-Danlos Syndrome
Lead sponsor: Acer Therapeutics Inc.
Sponsor class: INDUSTRY
First posted: 2022-06-27
Enrollment: 150
Sex: ALL
Minimum age (years): 15
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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

Primary outcomes:
measure: 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
timeFrame: Over the double-blind period (estimated to be 40 months)
Secondary outcomes:
measure: 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
timeFrame: Over the double-blind period (estimated to be 40 months)
measure: Number and percentage of patients with adverse events
timeFrame: Over the double-blind period (estimated to be 40 months)
measure: Number and percentage of Serious Adverse Events (SAE)
timeFrame: Over the double-blind period (estimated to be 40 months)
measure: Number and percentage of patient deaths
timeFrame: Over the double-blind period (estimated to be 40 months)
measure: Number and percentage of patient discontinuations
timeFrame: Over the double-blind period (estimated to be 40 months)
Other outcomes:
Locations:
city: Culver City
country: United States
facility: Science 37
state: California
Study officials:
References: