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

Sponsor
Washington University School of Medicine (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04611880
Collaborator
(none)
20
Enrollment
2
Locations
1
Arm
48
Anticipated Duration (Months)
10
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Trial of Crizanlizumab for the Treatment of Retinal Vasculopathy With Cerebral Leukoencephalopathy (RVCL)
Actual Study Start Date :
Jan 25, 2021
Anticipated Primary Completion Date :
Jan 25, 2023
Anticipated Study Completion Date :
Jan 25, 2025

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change in lesion pattern on Fluid-Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) in RVCL patients. [year]

      Volume change in lesions of FLAIR MRI between baseline and one year is assessed.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    25 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Andria Ford Saint Louis Missouri United States 63110
    2 Perelman School of Medicine; University of Pennsylvania Philadelphia Pennsylvania United States 19104

    Sponsors and Collaborators

    • Washington University School of Medicine

    Investigators

    • Principal Investigator: Andria Ford, MD, Washington University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT04611880
    Other Study ID Numbers:
    • 202008079
    First Posted:
    Nov 2, 2020
    Last Update Posted:
    Jan 28, 2022
    Last Verified:
    Jan 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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
    Additional relevant MeSH terms:
    Leukoencephalopathies
    Vascular Diseases

    Study Results

    No Results Posted as of Jan 28, 2022