Crizanlizumab for Treatment of Retinal Vasculopathy With Cerebral Leukoencephalopathy (RVCL)

February 13, 2023 updated by: Washington University School of Medicine

A Trial of Crizanlizumab for the Treatment of Retinal Vasculopathy With Cerebral Leukoencephalopathy (RVCL)

This is a Phase 2 trial that will test the efficacy and safety of crizanlizumab for the treatment of retinal vasculopathy with cerebral leukoencephalopathy (RVCL), a very rare and uniformly fatal genetic condition that affects the microvasculature, especially of the brain and eye. There currently is no treatment for RVCL. A maximum of 20 patients will be enrolled.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Retinal vasculopathy with cerebral leukoencephalopathy (RVCL) is a very rare and uniformly fatal genetic condition that affects the microvasculature, especially of the brain and eye. Symptoms begin in adulthood (usually in the mid-30s to early 40s) and include loss of vision, mini-strokes, and dementia. Other patients have suffered from microvascular disease involving the kidneys, osteonecrosis, and gut ischemia. Some of these features of microvascular occlusive disease resemble ischemic events that occur during sickle cell disease. Currently, there is no effective treatment for RVCL.

The goal of this study is to test the efficacy of RVCL patients treated with crizanlizumab, a humanized monoclonal anti-P-selectin antibody that prevents leukocyte adhesion to the vascular endothelium, thereby limiting risk of microvascular occlusion. P-selectin is mobilized to the surface of activated vascular endothelial cells and promotes leukocyte adhesion to the blood vessel wall. The Miner laboratory has preliminarily observed a correlation with levels of soluble P-selectin and the number of brain lesions in patients with RVCL. Since leukocyte adhesion to the vascular endothelium promotes microvascular occlusion, we will determine if crizanlizumab will help to limit ischemia and brain lesions in patients with RVCL. This may lead to the development of fewer ischemic brain and eye lesions.

Up to 20 RVCL patients will receive intravenous infusions of crizanlizumab 5 mg/kg at weeks 1 and 3. Thereafter, patients will receive crizanlizumab 5 mg/kg every 28 days for a total of 24 total months. Monitoring will include standard-of-care serial MRI as well as standard-of-care eye disease monitoring at pre-defined intervals. High-risk medication monitoring will include blood work monitoring (CBC/CMP) 1 month after initiation of treatment and every 3 months thereafter. Standard-of-care assessments will be performed including radiological and physical examinations as well as eye imaging and examinations. Patients will be followed for at least 2 years after completion of crizanlizumab administration.

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Andria Ford
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Perelman School of Medicine; University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. A diagnosis of RVCL with confirmation by genetic test
  2. At least 25 years of age with imaging evidence of brain or eye disease at the time of study registration
  3. Normal hematologic function defined as: White blood cell count (WBC) > 4x109/L, Absolute neutrophil count (ANC) >1.5x109/L and Platelets > 100x109/L
  4. Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on study drug and for 3 months after discontinuation from study drug, and must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc), barrier method contraception (i.e. condoms), or abstinence during that time-frame

  5. Able to understand and willing to sign an Internal Review Board (IRB)-approved written informed consent document (or that of legally authorized representative, if applicable)

    -

Exclusion Criteria:

  1. Acute bacterial, fungal, or viral infection
  2. Known HIV, untreated latent tuberculosis (TB), or active hepatitis B or C infection or zoster
  3. Pregnant and/or breastfeeding. Negative serum pregnancy test required prior to starting study treatment. For females of child-bearing potential (FCBP), a negative urine pregnancy test is required before each infusion.
  4. Known hypersensitivity to one or more of the study agents
  5. Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug
  6. Liver function tests (LFTs) higher than 3x the upper limit of normal within the last 30 days
  7. Treatment with other monoclonal antibody medications within the last 30 days

  8. Treatment with various forms of anticoagulation within last 30 days, including but not limited to clopidogrel or coumadin or direct thrombin inhibitors

    -

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Single Arm Study
Single arm study: crizanlizumab will be supplied in single use vials containing 10 mL at a concentration of 10 mg/mL for administration by IV infusion. Each patient will receive one dose of crizanlizumab on day 1 of Week 1, day 1 of Week 3, day 1 of Week 7, and then day 1 of every 4-week cycle. On infusion day, the pharmacist or designated personnel will prepare individual doses of crizanlizumab for subjects on a milligram per kilogram basis (5 mg/kg) in a 100 mL infusion bag in accordance with the Pharmacy Manual. Crizanlizumab will be administered over 30 minutes by IV infusion
Drug: Crizanlizumab
Drug: crizanlizumab is a humanized monoclonal anti-P-selectin antibody that prevents leukocyte adhesion to the vascular endothelium, thereby limiting risk of microvascular occlusion. It is administered intravenously.
Other Names:
  • ADAKVEO

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in lesion pattern on Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) in RVCL patients.
Time Frame: year
Volume change in lesions of FLAIR MRI between baseline and one year is assessed.
year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 25, 2021

Primary Completion (ANTICIPATED)

January 1, 2024

Study Completion (ANTICIPATED)

August 25, 2027

Study Registration Dates

First Submitted

October 26, 2020

First Submitted That Met QC Criteria

October 26, 2020

First Posted (ACTUAL)

November 2, 2020

Study Record Updates

Last Update Posted (ESTIMATE)

February 14, 2023

Last Update Submitted That Met QC Criteria

February 13, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202008079

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be shared among the principle investigator and the other investigators

IPD Sharing Time Frame

immediate

IPD Sharing Access Criteria

Individual Patient Data (IPD) will be available on REDCap or as provided by principal investigator

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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