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

NCT04611880 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 202008079
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

RVCL - Retinal Vasculopathy Cerebral Leukoencephalopathy

Outcome Measures

Primary Outcomes (1)

• Change in the Percentage of White Matter Hyperintensity (WMH) Lesion Volume on FLAIR MRI in RVCL Patients

  At each study time-point, the white matter hyperintensity lesion volume (mL) was normalized to whole-brain volume (mL) and then log-transformed, from which the annualized percent change in the log-transformed normalized WMH volume was calculated.

  1 year

Study Arms (1)

Single Arm Study

OTHER

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

Interventions

Crizanlizumab DRUG

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.

Also known as: ADAKVEO

Single Arm Study

Eligibility Criteria

• Age: 25 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Normal hematologic function defined as: White blood cell count (WBC) \> 4x109/L, Absolute neutrophil count (ANC) \>1.5x109/L and Platelets \> 100x109/L
• 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
• 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)

You may not qualify if:

• Acute bacterial, fungal, or viral infection
• Known HIV, untreated latent tuberculosis (TB), or active hepatitis B or C infection or zoster
• 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.
• Known hypersensitivity to one or more of the study agents
• Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug
• Liver function tests (LFTs) higher than 3x the upper limit of normal within the last 30 days
• Treatment with other monoclonal antibody medications within the last 30 days
• Treatment with various forms of anticoagulation within last 30 days, including but not limited to clopidogrel or coumadin or direct thrombin inhibitors

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (2)

Andria Ford

St Louis, Missouri, 63110, United States

Location

Perelman School of Medicine; University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (6)

• Kavanagh D, Spitzer D, Kothari PH, Shaikh A, Liszewski MK, Richards A, Atkinson JP. New roles for the major human 3'-5' exonuclease TREX1 in human disease. Cell Cycle. 2008 Jun 15;7(12):1718-25. doi: 10.4161/cc.7.12.6162. Epub 2008 Jun 16.

  PMID: 18583934 BACKGROUND

• Hasan M, Fermaintt CS, Gao N, Sakai T, Miyazaki T, Jiang S, Li QZ, Atkinson JP, Morse HC 3rd, Lehrman MA, Yan N. Cytosolic Nuclease TREX1 Regulates Oligosaccharyltransferase Activity Independent of Nuclease Activity to Suppress Immune Activation. Immunity. 2015 Sep 15;43(3):463-74. doi: 10.1016/j.immuni.2015.07.022. Epub 2015 Aug 25.

  PMID: 26320659 BACKGROUND

• Wood KC, Hebbel RP, Granger DN. Endothelial cell P-selectin mediates a proinflammatory and prothrombogenic phenotype in cerebral venules of sickle cell transgenic mice. Am J Physiol Heart Circ Physiol. 2004 May;286(5):H1608-14. doi: 10.1152/ajpheart.01056.2003. Epub 2004 Jan 2.

  PMID: 14704223 BACKGROUND

• McEver RP, Cummings RD. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest. 1997 Dec 1;100(11 Suppl):S97-103. No abstract available.

  PMID: 9413410 BACKGROUND

• Ford AL, Chin VW, Fellah S, Binkley MM, Bodin AM, Balasetti V, Taiwo Y, Kang P, Lin D, Jen JC, Grand MG, Bogacki M, Liszewski MK, Hourcade D, Chen Y, Hassenstab J, Lee JM, An H, Miner JJ, Atkinson JP. Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy. Neurology. 2020 Oct 6;95(14):e1918-e1931. doi: 10.1212/WNL.0000000000010659. Epub 2020 Sep 4.

  PMID: 32887784 BACKGROUND

• Wang WX, Spiegelman D, Rao PK, Rhee RL, Ford AL, Miner JJ, Apte RS. Crizanlizumab for retinal vasculopathy with cerebral leukoencephalopathy in a phase II clinical study. J Clin Invest. 2024 May 7;134(12):e180916. doi: 10.1172/JCI180916.

  PMID: 38950286 DERIVED

Related Links

• RVCL Research and Treatment Center

MeSH Terms

Conditions

Vasculopathy, Retinal, With Cerebral Leukodystrophy

Interventions

crizanlizumab

Results Point of Contact

• Title: Andria Ford, MD
• Organization: Washington University School of Medicine

forda@wustl.edu

314-362-7382

Study Officials

• Andria Ford, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2020
• First Posted: November 2, 2020
• Study Start: January 25, 2021
• Primary Completion: April 2, 2025
• Study Completion: December 31, 2025
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: immediate
• Access Criteria: Individual Patient Data (IPD) will be available on REDCap or as provided by principal investigator

Locations

US (2)