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

Acer Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: Vascular Ehlers-Danlos Syndrome

Treatments: Drug: ACER-002 (celiprolol) 200 mg BID; Drug: Placebo BID

Study type: Interventional

Funder types: Industry

Identifiers

NCT05432466

ACER-002-301

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 15 to 64 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

150 participants in 2 patient groups

ACER-002 (celiprolol) 200 mg BID

Experimental group

Description:

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

Treatment:

Drug: ACER-002 (celiprolol) 200 mg BID

Placebo BID

Experimental group

Description:

Placebo twice daily (BID) Placebo given orally to mimic ACER-002 (celiprolol) administration

Treatment:

Drug: Placebo BID