Study of Crizanlizumab for Prevention of Silent Cerebral Infarcts in SCA (CRIZ)
Primary Purpose
Sickle Cell Disease
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Crizanlizumab
Sponsored by
About this trial
This is an interventional prevention trial for Sickle Cell Disease
Eligibility Criteria
Inclusion Criteria:
- Adult participants age 16 and older
- Sickle cell disease with confirmation of HbSS, HbSBthal0, HbSC, or HbS thal+ genotype
Per patient's sickle cell provider, patient has an increased risk of a silent cerebral infarcts according to one of the following criteria:
- Silent cerebral infarcts visualized on FLAIR MRI within previous two years
- Intracranial or extracranial cervical artery vasculopathy
- History of overt ischemic or hemorrhagic stroke and Intolerance and/or failure of other therapies to prevent cerebral infarction
- 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).
- Increased risk deemed by other objective laboratory and/or imaging results which have been associated with increased risk of cerebral infarction
- Provide written informed consent.
- Normal hematologic function defined as: WBC > 4x10^9 / L, ANC >1.5x10^9 / L and platelets > 100x10^9 / L
- 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:
- Current chronic transfusion therapy
- Planning for hematopoietic stem cell transplant or cerebral revascularization procedure
- Use of other investigational drug within one year of study participation
- Other medical/neurological/social/substance abuse history that would alter brain MRI findings prospectively
- Inability to return for follow-up
- Contraindication to MRI
- 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 pregnancy test required prior to starting study treatment.
- 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 (LFT) higher than 3x the upper limit of normal
- Treatment with other monoclonal antibody medications within last 30 days
- Treatment with various forms of anticoagulation within last 30 days, including but not limited to coumadin or direct thrombin inhibitors
Sites / Locations
- Barnes-Jewish HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Single Arm: Crizanlizumab
Arm Description
Single-arm: Patients with sickle cell disease and increased risk of silent cerebral infarcts
Outcomes
Primary Outcome Measures
New or enlarged silent cerebral infarcts
Occurrence of 'new or enlarged' silent cerebral infarcts between the baseline and 30 month follow-up scan.
Secondary Outcome Measures
Infarct Progression
Change in volume of silent cerebral infarcts between the baseline and 30 month follow-up scan.
Full Information
NCT ID
NCT05334576
First Posted
November 30, 2021
Last Updated
March 2, 2023
Sponsor
Andria Ford
Collaborators
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05334576
Brief Title
Study of Crizanlizumab for Prevention of Silent Cerebral Infarcts in SCA
Acronym
CRIZ
Official Title
Study of Crizanlizumab for Prevention of Silent Cerebral Infarcts in SCA Novartis Investigator Initiated Trial: CSEG101AUS12T
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2022 (Actual)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
July 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Andria Ford
Collaborators
Novartis Pharmaceuticals
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Crizanlizumab (SEG101) at 5.0 mg/kg dose administered over two years per standard of care in patients with sickle cell disease and silent cerebral infarcts.
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single Arm: Crizanlizumab
Arm Type
Other
Arm Description
Single-arm: Patients with sickle cell disease and increased risk of silent cerebral infarcts
Intervention Type
Other
Intervention Name(s)
Crizanlizumab
Intervention Description
Crizanlizumab 5.0 mg/kg infusions will be administered over 24 months
Primary Outcome Measure Information:
Title
New or enlarged silent cerebral infarcts
Description
Occurrence of 'new or enlarged' silent cerebral infarcts between the baseline and 30 month follow-up scan.
Time Frame
30 months
Secondary Outcome Measure Information:
Title
Infarct Progression
Description
Change in volume of silent cerebral infarcts between the baseline and 30 month follow-up scan.
Time Frame
30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult participants age 16 and older
Sickle cell disease with confirmation of HbSS, HbSBthal0, HbSC, or HbS thal+ genotype
Per patient's sickle cell provider, patient has an increased risk of a silent cerebral infarcts according to one of the following criteria:
Silent cerebral infarcts visualized on FLAIR MRI within previous two years
Intracranial or extracranial cervical artery vasculopathy
History of overt ischemic or hemorrhagic stroke and Intolerance and/or failure of other therapies to prevent cerebral infarction
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).
Increased risk deemed by other objective laboratory and/or imaging results which have been associated with increased risk of cerebral infarction
Provide written informed consent.
Normal hematologic function defined as: WBC > 4x10^9 / L, ANC >1.5x10^9 / L and platelets > 100x10^9 / L
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:
Current chronic transfusion therapy
Planning for hematopoietic stem cell transplant or cerebral revascularization procedure
Use of other investigational drug within one year of study participation
Other medical/neurological/social/substance abuse history that would alter brain MRI findings prospectively
Inability to return for follow-up
Contraindication to MRI
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 pregnancy test required prior to starting study treatment.
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 (LFT) higher than 3x the upper limit of normal
Treatment with other monoclonal antibody medications within last 30 days
Treatment with various forms of anticoagulation within last 30 days, including but not limited to coumadin or direct thrombin inhibitors
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andria Ford, MD
Phone
314-362-7382
Email
forda@wustl.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Nkemdilim N Igwe, MS
Phone
314-503-2161
Email
igwe@wustl.edu
Facility Information:
Facility Name
Barnes-Jewish Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andria L. Ford
Phone
314-747-4037
Email
forda@wustl.edu
First Name & Middle Initial & Last Name & Degree
Nkemdilim Igwe, MS, MSCI
Phone
(314) 503-2161
Email
igwe@wustl.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Crizanlizumab for Prevention of Silent Cerebral Infarcts in SCA
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