Crizanlizumab for RVCL

Not currently recruiting at 2 trial locations

Overseen By Andria Ford, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Monoclonal antibodies, Anticoagulants

Disqualifiers: Infections, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of crizanlizumab, administered through IV infusion, in treating retinal vasculopathy with cerebral leukoencephalopathy (RVCL). RVCL is a rare and severe genetic condition affecting small blood vessels in the brain and eyes, with no current treatment available. The trial seeks individuals with a confirmed genetic diagnosis of RVCL and symptoms of brain or eye disease. Participants will receive crizanlizumab infusions on a set schedule to assess its impact on managing their condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as other monoclonal antibody medications and anticoagulants, at least 30 days before starting the study drug. If you are on any investigational drugs, you must stop them 14 days before the trial begins.

Is there any evidence suggesting that crizanlizumab is likely to be safe for humans?

Research has shown that crizanlizumab is generally safe, meaning most patients in studies tolerated it well. Although specific side effect details from these studies are not available, the treatment appears promising for further testing in larger studies. As this trial is in Phase 2, crizanlizumab has already passed initial safety tests, which should provide some confidence in its safety for potential trial participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Crizanlizumab is unique because it targets a specific pathway in the immune system called P-selectin, which plays a crucial role in inflammation and blood vessel damage. Unlike standard treatments for RVCL, which often focus on managing symptoms, crizanlizumab works by preventing the underlying cause of these blood vessel issues. Researchers are excited because this approach could lead to more effective management of RVCL, potentially reducing complications and improving quality of life for patients.

What evidence suggests that crizanlizumab might be an effective treatment for RVCL?

Research has shown that crizanlizumab targets a protein called P-selectin, which plays a role in inflammation and blood vessel issues. It is already approved to help prevent pain in people with sickle cell disease. Although direct evidence for its use in RVCL is limited, early research suggests it might be beneficial because RVCL also affects small blood vessels. By blocking P-selectin, crizanlizumab may reduce inflammation and improve blood flow, potentially slowing the damage caused by RVCL. However, more studies are needed to confirm its effectiveness for this rare condition. Participants in this single-arm trial will receive crizanlizumab to further investigate its potential benefits for RVCL. ^{1 2 3 4 6}

Who Is on the Research Team?

Andria Ford, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have been diagnosed with RVCL through a genetic test.

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

Your blood counts for white cells, neutrophils, and platelets are within normal range.

Exclusion Criteria

You are allergic to any of the medications being used in the study.

Your liver function tests showed results more than three times the normal range in the last 30 days.

I have taken blood thinners like clopidogrel or coumadin in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusions of crizanlizumab 5 mg/kg at weeks 1 and 3, and then every 4 weeks for a total of 24 months

24 months

Infusions at weeks 1, 3, 7, and every 4 weeks thereafter

Monitoring

Standard-of-care serial MRI and eye disease monitoring, along with blood work monitoring (CBC/CMP) 1 month after initiation and every 3 months thereafter

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Crizanlizumab

Trial Overview

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.

How Is the Trial Designed?

Group I: Single Arm Study Experimental Treatment 1 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

Crizanlizumab is already approved in United States for the following indications:

Approved in United States as Adakveo for:

• Prevention of recurrent vaso-occlusive crises in sickle cell disease patients aged 16 years and older

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Crizanlizumab is the first monoclonal antibody approved for sickle cell disease, specifically designed to reduce the frequency of vaso-occlusive pain crises, based on data from a phase 2 clinical trial.

This medication is administered as a monthly intravenous infusion for patients aged 16 and older, showing efficacy in crisis prevention, although concerns about cost and long-term safety remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease. Stevens, DL., Hix, M., Gildon, BL.[2022]

Crizanlizumab is a monoclonal antibody that effectively reduces the frequency of vaso-occlusive crises (VOCs) in patients with sickle cell disease by blocking P-selectin, which is crucial for cell adhesion and inflammation.

Approved in the USA in November 2019 for adults and pediatric patients aged 16 and older, crizanlizumab is also under review in the EU and being studied for use in myelofibrosis, indicating its potential versatility in treating blood-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizanlizumab: First Approval. Blair, HA.[2020]

Crizanlizumab effectively reduces the frequency of vaso-occlusive crises (VOCs) in patients with sickle cell disease, showing a significant reduction in the annualized rate of VOCs after more than 12 months of treatment, with a median reduction of -0.88 and -0.93 for the 5.0 mg/kg and 7.5 mg/kg doses, respectively.

The treatment demonstrated a favorable safety profile, with only one treatment-related adverse event reported and no serious treatment-related adverse events, indicating that crizanlizumab can be safely administered over long periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. Kanter, J., Brown, RC., Norris, C., et al.[2023]

Crizanlizumab, a monoclonal antibody targeting P-selectin, received conditional marketing authorization in the EU for preventing recurrent vaso-occlusive crises in sickle cell disease patients aged 16 and older, showing a 45.3% reduction in annual pain crises at a high dose compared to placebo.

The treatment was found to have a similar safety profile to placebo, with common side effects including infusion-related reactions and arthralgia, indicating that crizanlizumab is both effective and relatively safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease. Delgado, J., Voltz, C., Stain, M., et al.[2021]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38950286/

Crizanlizumab for retinal vasculopathy with cerebral ... - PubMed

This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the prevention of ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04611880

NCT04611880 | Crizanlizumab for Treatment of Retinal ...

This is a Phase 2 trial that will test the efficacy and safety of crizanlizumab for the treatment of retinal vasculopathy with cerebral leukoencephalopathy ...

3.

jci.org

jci.org/articles/view/180916

Crizanlizumab for retinal vasculopathy with cerebral ...

This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the prevention of ...

4.

digitalcommons.wustl.edu

digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=4887&context=oa_4

Crizanlizumab for retinal vasculopathy with cerebral ...

This study explores the safety and preliminary efficacy of crizanlizumab, a humanized monoclonal antibody against P-selectin approved for the ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2666245022000113

Retinal Vasculopathy with Cerebral Leukoencephalopathy ...

There is an ongoing trial studying the effectiveness of crizanlizumab (NCT04611880) for treating RVCL-S of which there are no results yet. Further research ...

6.

jci.org

jci.org/articles/view/189023

Crizanlizumab for retinal vasculopathy with cerebral ...

In RVCL-S patients receiving crizanlizumab, we have observed clear progression of brain lesions based on MRI results. A detailed analysis of the ...