What is the mechanism of action of this treatment?

Crizanlizumab, a P-selectin inhibitor, works by blocking the P-selectin protein on endothelial cells and platelets, thereby preventing the interaction between these cells and leukocytes. This reduces inflammation and vascular occlusion, which are critical in managing Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). For RVCL patients, this mechanism is significant because the disease involves microvascular damage in the brain and eyes, leading to severe complications. By reducing inflammation and preventing vascular blockages, Crizanlizumab could potentially alleviate symptoms and slow disease progression.

What side effects are associated with this type of intervention?

Crizanlizumab, a P-selectin inhibitor, is currently being studied for the treatment of Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). While specific side effects for crizanlizumab in RVCL are not detailed, P-selectin inhibitors generally may cause side effects such as infusion reactions, including fever, chills, and rash. Broader treatments for retinal vasculopathy can include ocular side effects like inflammation, infection, and potential vision changes. It is important to discuss potential side effects with a healthcare provider to understand the risks and benefits of the treatment.

What prior FDA approvals exist?

There are currently no FDA-approved treatments specifically for Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). The trial mentioned is investigating the efficacy and safety of Crizanlizumab, a P-selectin inhibitor, for this condition. This is a novel approach as there are no existing treatments targeting P-selectin inhibition for RVCL.

← Back to Search

Monoclonal Antibodies

Crizanlizumab for RVCL

Q: What other types of research exist?

As of 2024, Crizanlizumab remains the primary investigational treatment for Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). No other novel alternatives have been specified in the current research context.

Phase 2

Waitlist Available

Led By Andria Ford, MD

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

A diagnosis of RVCL with confirmation by genetic test

At least 25 years of age with imaging evidence of brain or eye disease at the time of study registration

Must not have

Treatment with other monoclonal antibody medications within the last 30 days

Known HIV, untreated latent tuberculosis (TB), or active hepatitis B or C infection or zoster

Timeline

Screening 3 weeks

Treatment Varies

Follow Up year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests crizanlizumab, a medication that prevents blood cells from sticking to vessel walls, in patients with a rare and fatal condition called RVCL. The goal is to see if it can reduce brain and eye damage by preventing small blood vessel blockages. Crizanlizumab is a monoclonal antibody developed by Novartis Pharmaceuticals for the prevention of vaso-occlusive crises in patients with sickle cell disease.

Who is the study for?

This trial is for adults over 25 with a rare, fatal genetic condition called RVCL confirmed by genetic testing. Participants must not be pregnant or breastfeeding and agree to use contraception. They should have normal blood counts, no recent infections, HIV, hepatitis B/C, or TB, and haven't taken certain medications recently.

What is being tested?

The study is evaluating the effectiveness and safety of Crizanlizumab in treating RVCL. This Phase 2 trial aims to enroll up to 20 patients who suffer from this condition that severely affects brain and eye blood vessels.

What are the potential side effects?

Potential side effects are not explicitly listed but may include reactions typical of monoclonal antibody treatments such as infusion reactions, immune system changes, or allergic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with RVCL through a genetic test.

Select...

I am 25 or older and have brain or eye disease confirmed by imaging.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I haven't taken any monoclonal antibody medications in the last 30 days.

Select...

I have HIV, untreated TB, hepatitis B or C, or shingles.

Select...

I currently have an acute infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~year

This trial's timeline: 3 weeks for screening, Varies for treatment, and year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

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

Side effects data

From 2021 Phase 2 trial • 54 Patients • NCT04435184

Chest pain

Headache

Diarrhea

Dark and Infrequent Urination

Venous thrombembolism

Altered mental status

100%

80%

60%

40%

20%

Study treatment Arm

Crizanlizumab

Placebo Saline

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Single Arm StudyExperimental Treatment1 Intervention

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Crizanlizumab

2021

Completed Phase 2

~640

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Crizanlizumab, a P-selectin inhibitor, works by blocking the P-selectin protein on endothelial cells and platelets, thereby preventing the interaction between these cells and leukocytes. This reduces inflammation and vascular occlusion, which are critical in managing Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). For RVCL patients, this mechanism is significant because the disease involves microvascular damage in the brain and eyes, leading to severe complications. By reducing inflammation and preventing vascular blockages, Crizanlizumab could potentially alleviate symptoms and slow disease progression.

[Real-life experiences with Brolucizumab in recalcitrant neovascular age-related macular degeneration].The effect of antivascular endothelial growth factor therapy on the development of neovascular glaucoma after central retinal vein occlusion: a retrospective analysis.Valsartan and retinal endothelial function in elderly hypertensive patients.