Study of Crizanlizumab for Prevention of Silent Cerebral Infarcts in SCA (CRIZ)

Study of Crizanlizumab for Prevention of Silent Cerebral Infarcts in SCA Novartis Investigator Initiated Trial: CSEG101AUS12T

In this prospective, single-arm, open-label, imaging and treatment study, the investigator will test the hypothesis that crizanlizumab will prevent the progression of silent cerebral infarcts in patients with sickle cell disease. Study participants will undergo brain MRI before initiation of crizanlizumab and at 6 and 30 months after starting crizanlizumab infusions. The crizanlizumab cohort will be compared to a matched, observational cohort of patients not receiving crizanlizumab.

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Other: Crizanlizumab

• Study Type: Interventional
• Enrollment (Anticipated): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Barnes-Jewish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult participants age 16 and older
2. Sickle cell disease with confirmation of HbSS, HbSBthal0, HbSC, or HbS thal+ genotype

3. Per patient's sickle cell provider, patient has an increased risk of a silent cerebral infarcts according to one of the following criteria:

   1. Silent cerebral infarcts visualized on FLAIR MRI within previous two years
   2. Intracranial or extracranial cervical artery vasculopathy
   3. History of overt ischemic or hemorrhagic stroke and Intolerance and/or failure of other therapies to prevent cerebral infarction
   4. Increased severity of sickle cell disease including having between 2 and 10 sickle cell-related pain crises within the preceding 12 months as determined by medical history or by patient's recall (crises should include the occurrence of appropriate symptoms, a visit to a specific medical facility and/or health care professional, and receipt of pain medication).
   5. Increased risk deemed by other objective laboratory and/or imaging results which have been associated with increased risk of cerebral infarction
4. Provide written informed consent.
5. Normal hematologic function defined as: WBC > 4x10^9 / L, ANC >1.5x10^9 / L and platelets > 100x10^9 / L
6. Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on crizanlizumb and for 3 months after discontinuation from crizanlizumab, 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 the time-frame

Exclusion Criteria:

1. Current chronic transfusion therapy
2. Planning for hematopoietic stem cell transplant or cerebral revascularization procedure
3. Use of other investigational drug within one year of study participation
4. Other medical/neurological/social/substance abuse history that would alter brain MRI findings prospectively
5. Inability to return for follow-up
6. Contraindication to MRI
7. Acute bacterial, fungal, or viral infection
8. Known HIV, untreated latent tuberculosis (TB), or active hepatitis B or C infection or zoster
9. Pregnant and/or breastfeeding. Negative pregnancy test required prior to starting study treatment.
10. Known hypersensitivity to one or more of the study agents
11. Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug
12. Liver function tests (LFT) higher than 3x the upper limit of normal
13. Treatment with other monoclonal antibody medications within last 30 days
14. Treatment with various forms of anticoagulation within last 30 days, including but not limited to coumadin or direct thrombin inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Single Arm: Crizanlizumab; Single-arm: Patients with sickle cell disease and increased risk of silent cerebral infarcts	Other: Crizanlizumab; Crizanlizumab 5.0 mg/kg infusions will be administered over 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New or enlarged silent cerebral infarcts	Occurrence of 'new or enlarged' silent cerebral infarcts between the baseline and 30 month follow-up scan.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarct Progression	Change in volume of silent cerebral infarcts between the baseline and 30 month follow-up scan.	30 months

Collaborators and Investigators

• Sponsor: Andria Ford
• Collaborators: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): July 1, 2025

Study Registration Dates

• First Submitted: November 30, 2021
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 19, 2022

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Brain Ischemia; Infarction; Stroke; Brain Infarction; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Cerebral Infarction; Anemia, Sickle Cell
• Other Study ID Numbers: CSEG101AUS12T

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No