Vascular Ehlers-Danlos Syndrome
Conditions
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.
Interventions
DRUGACER-002 (celiprolol) 200 mg BID
ACER-002 (celiprolol) 200 mg BID
DRUGPlacebo BID
placebo for ACER-002
Sponsors
Acer Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes 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).
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.
Eligibility
Sex/Gender
ALL
Age
15 Years to 64 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Contacts
Primary ContactSheila Woodhouse, MD; Ph.D.
Backup ContactJonathan Cotliar, MD; Ph.D.
Outcome results
None listed