Crizanlizumab for RVCL

Recruiting at 1 trial location

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

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

How is the drug crizanlizumab unique for treating RVCL?

Crizanlizumab is unique because it is a monoclonal antibody that targets P-selectin, a molecule involved in blood vessel blockages, and is administered through an intravenous infusion. While it is primarily used to prevent pain crises in sickle cell disease, its mechanism of action may offer novel benefits for conditions like RVCL, where there are no standard treatments. ^{1 2 3 4 5}

Research Team

Andria Ford, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Crizanlizumab: First Approval. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Crizanlizumab for the Prevention of Vaso-Occlusive Pain Crises in Sickle Cell Disease. [2022]

3. United States 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics and Pharmacodynamics of Crizanlizumab in Healthy Subjects and Patients with Sickle Cell Disease. [2023]