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Trial record 1 of 6 for:    crizanlizumab and Novartis | Sickle Cell Disease
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Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03474965
Recruitment Status : Recruiting
First Posted : March 23, 2018
Last Update Posted : August 14, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of the Phase 2 CSEG101B2201 study is to confirm and to establish appropriate dosing and to evaluate the safety in pediatric participants ages 6 months to <18 years with a history of VOC with or without HU/HC, receiving crizanlizumab for 2 years. The efficacy and safety of crizanlizumab was already demonstrated in adults with sickle cell disease. The approach is to extrapolate from the PK/pharmacodynamics (PD) already established in the adult population. The study is designed as a Phase II, multicenter, open-label study.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease (SCD) Drug: Crizanlizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2,Multicenter,Open-Label Study to Assess Appropriate Dosing and to Evaluate Safety of Crizanlizumab,With or Without Hydroxyurea/Hydroxycarbamide,in Sequential,Descending Age Groups of Pediatric Sickle Cell Disease Patients With Vaso-Occlusive Crisis
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : June 5, 2023
Estimated Study Completion Date : November 20, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Crizanlizumab
SEG101 (crizanlizumab) administered on Week 1 Day 1, Week3 Day 1 and Day 1 of every 4-week cycle
Drug: Crizanlizumab
Crizanlizumab (SEG101) is a concentrate for solution for infusion, i.v. use. Supplied in single use 10 mL vials at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab.
Other Name: SEG101




Primary Outcome Measures :
  1. PK (AUCd15) after 1st dose [ Time Frame: Day 15 ]
    Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A)

  2. PD (AUCd15) after 1st dose [ Time Frame: Day 15 ]
    Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A)

  3. PK (AUCtau) after multiple dose [ Time Frame: Week 15 ]
    Confirm appropriate dosing of Crizanlizumab in participants aged 2 to < 18 years old

  4. PD (AUCtau) after multiple dose [ Time Frame: Week 15 ]
    Confirm appropriate dosing of Crizanlizumab in participants aged 2 to < 18 years old

  5. PK (Cmax) after 1st dose and multiple dose [ Time Frame: Week 1 and Week 15 ]
    Confirm appropriate dosing of crizanlizumab in participants aged 2 to < 18 years (Parts A)

  6. PK pre-dose concentrations [ Time Frame: Week 1 to Week 19 ]
    Confirm appropriate dosing of crizanlizumab in participants aged 6 months to less than 24 months of age (Part B)

  7. Frequency of any adverse events (AEs) as a measure of safety and tolerability [ Time Frame: 6 months, 2 years ]
    Safety of crizanlizumab in participants aged 6 months to < 18 years (Parts A and B)


Secondary Outcome Measures :
  1. Annualized rate Vaso Occusive Crisis (VOC) events leading to healthcare visit in clinic/ER/hospital [ Time Frame: 6 months, 2 years ]
    To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)

  2. Annualized rate Vaso Occusive Crisis (VOC) events treated at home (based on documentation by health care provider following phone contact with the patient) [ Time Frame: 6 months, 2 years ]
    To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)

  3. Annualized rate each subcategory of VOC event (uncomplicated pain crisis, acute chest syndrome, hepatic sequestration, splenic sequestration, priapism) [ Time Frame: 6 months, 2 years ]
    To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)

  4. Annualized rate hospitalizations and ER visits (both overall and VOC-related) [ Time Frame: 6 months, 2 years ]
    To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)

  5. Annualized rate days of ER/hospitalization (both overall and VOC-related) [ Time Frame: 6 months, 2 years ]
    To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)

  6. Annualized rate of dactylitis events [ Time Frame: 6 months, 2 years ]
    To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old participants at the time of study entry (Parts A and B)

  7. Number, seriousness, severity, and causality assessments of treatement emergent adverse events and other data as considered appropiate. [ Time Frame: 6 months, 2 years ]
    To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry

  8. Absolute change from baseline in hemoglobin [ Time Frame: Baseline, 6 months, 2 years ]
    To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry

  9. Immunogenicity: measurement of anti-drug antibodies (ADA) to crizanlizumab [ Time Frame: Week 1, Week 3, Week 15, Week 27 and End of Treatment (EOT) ]
    To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry

  10. Electrocardiogram (ECGs) at relevant PK time points [ Time Frame: Screening, Week 7, Week 11, week 15, week 27 and Week 51 ]
    To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry

  11. Growth and sexual maturation assessments (Tanner stage) [ Time Frame: Screening, Week 51 and End of Treatment (EOT) ]
    To assess other safety measures in participants aged 6 months to < 18 years at the time of study entry

  12. PK pre-dose concentrations prior to each study drug dose. [ Time Frame: Week 1, Week 3, Week 7, Week 15, Week 19, Week 23, Week 27, Week 31, Week 35, Week 39, Week 43, Week 47 and Week 51 ]
    Characterize long-term PK and PD of crizanlizumab in participants aged 6 months to >18 years

  13. Percentage P-selectin inhibition prior to dosing [ Time Frame: Week 3, Week 15, Week 27 and Week 51 ]
    Characterize long-term PK and PD of crizanlizumab in participants aged 6 months to >18 years



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female patients ages 2 to <18 years (Group 3 will be expanded to allow enrolment of patients ages 6 to <24 months (and at least 7 kg) in Part B once the appropriate dose is confirmed in 2 to <6 year old participants).
  2. Confirmed diagnosis of SCD (any genotype including HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia patients, and others) by hemoglobin electrophoresis or/and high-performance liquid chromatography (HPLC) [performed locally]. Confirmation of diagnosis by two accepted methods is recommended.
  3. Experienced at least 1 VOC within the preceding 12 months prior to screening, as determined by medical history. Prior VOC must have resolved at least 7 days prior to the first dose in the study and must include all the following: a.the occurrence of appropriate symptoms (see VOC definition in Section 7.2.1.1), b.either a visit to a medical facility or healthcare professional, c.receipt of oral/parenteral opioid or parenteral NSAIDs
  4. If receiving HU/HC, L-glutamine or erythropoietin stimulating agent, must have been receiving the drug consistently for at least 6 months prior to screening and plan to continue taking it at the same dose and schedule during the trial. Patients who have not been receiving such drugs must have been off them for at least 6 months prior to screening. Dose alterations of HU/HC during Part A are not allowed, and if this occurs, the participant will enter directly to Part B.
  5. Received standard age-appropriate care for SCD, including penicillin prophylaxis, pneumococcal immunization, and parental education.
  6. Performance status: Karnofsky ≥ 50% for patients >10 years of age, and Lansky ≥ 50 for patients ≤ 10 years of age.
  7. Patient must meet the following laboratory values prior to Week 1 Day 1: Absolute Neutrophil Count ≥1.0 x 109/L , Platelets ≥75 x 109/L, Hemoglobin (Hgb) > 5.5 g/dL
  8. Patient must have adequate renal and hepatic function as defined:Estimated Glomerular filtration rate (eGFR) ≥ 75 mL/min/1.73 m2 using Schwartz formula, Direct (conjugated) bilirubin ≤ 2.0 x ULN, Alanine transaminase (ALT) ≤ 3.0 x ULN,
  9. Transcranial Doppler (TCD) for patients aged 2 to < 16 years at time of screening, with HbSS, HbSβ0-thalassemia, and HbSD disease indicating low risk for stroke (per investigator). Please refer to Section 7.2.2.6 for details
  10. Written informed consent/assent, according to local guidelines, signed by the patient and / or by the parents or legal guardian prior to any study related screening procedures are performed.
  11. Female of non-childbearing potential or with negative serum pregnancy test on Screening and a negative urine pregnancy test (dipstick) prior to dosing on Day 1.

Exclusion Criteria:

  1. History of stem cell transplant.
  2. Received any blood products within 30 days prior to Week 1 Day 1 dosing.
  3. Plan to participate in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) or undergo exchange transfusions/plasmapheresis during the study. Patients requiring episodic transfusion (simple or exchange) in response to worsened anemia or VOC are permitted.
  4. Patients with bleeding disorders

6.Contraindication or hypersensitivity to any drug from similar class as study drug or to any excipients of the study drug formulation.

7.History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction 8.Received a monoclonal antibody or immunoglobulin-based therapy within 6 months of Screening, or has documented immunogenicity to a prior monoclonal antibody.

9.Received active treatment on another investigational trial within 30 days (or 5 half -lives of that agent, whichever is greater) prior to Screening or plans to participate in another investigational drug trial.

10.Pregnant females or females who have given birth within the past 90 days or who are breastfeeding.

11.Any documented history of a clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months. Silent infarcts (only present on imaging) are not excluded.

12.Any abnormal TCD within the past 12 months. 13.Use of therapeutic anticoagulation (prophylactic doses permitted) or antiplatelet therapy (other than aspirin) within the 10 days prior to Week 1 Day 1 dosing.

14.Hospitalized within 7 days prior to Week 1 Day 1 dosing. 15.Planning to undergo a major surgical procedure during the duration of the study.

16.Planning to initiate or terminate HU/HC or L-glutamine while on study (except if needed to terminate for safety reasons).

17.Patient with active human immunodeficiency virus (HIV) infection (detectable viral load).

18.Patients with known active Hepatitis B infection. 19.Patients with known Hepatitis C history. 20.Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator.

21.Malignant disease. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; any completely resected carcinoma in situ.

22.Has a serious mental or physical illness, which, in the opinion of the Investigator would compromise participation in the study.

23.Any condition which, in the opinion of the investigator, is likely to interfere with the successful collection of the measurements required for the study 24.Resting QTcF ≥450 msec at pretreatment (baseline) for patients under 12 years of age and ≥450 msec for males and ≥460 msec for female patients 12 years and older.

25.Cardiac or cardiac repolarization abnormality, including any of the following: a.History of myocardial infarction (MI), uncontrolled congestive heart failure, unstable angina, or coronary bypass graft (CABG) within 6 months prior to starting study treatment, b.Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (bifascicular block, Mobitz Type II, and third degree AV block), c. Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome ( Risk factors for Torsade de Pointes (TdP), including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/ symptomatic bradycardia, Inability to determine the QTcF).

26. Sexually active females who are unwilling to comply with reliable method of birth control until 15 weeks following last dose of study drug.

28.Not able to understand and to comply with study instructions and requirements.

29.Patients who are an employee of the sponsor or investigator or otherwise dependent on them.

30.Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

31.Patients who received prior crizanlizumab treatment are not allowed. 32.Patients having taken voxelotor less than 30 days prior to Screening, or planning to take voxelotor while on study are not allowed.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03474965


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Alabama
University of Alabama 1600 7th ave Recruiting
Birmingham, Alabama, United States, 35233
Contact: Christy Patrick    205-638-9285    cpatrick@peds.uab.edu   
Principal Investigator: Thomas Howard         
United States, Arizona
Phoenix Childrens Hospital CVAL489A2302 Recruiting
Phoenix, Arizona, United States, 85016
Contact: Courtney Moyer    602-546-4702    cmoyer@phoenixchildrens.com   
Principal Investigator: Sanjay Shah         
United States, California
UC Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Michelle Adams    916-734-2011    msadams@ucdavis.edu   
Principal Investigator: Jo Chung         
United States, District of Columbia
Children s National Hospital Recruiting
Washington, District of Columbia, United States, 20010
Contact: Stefanie Jesus Margulies    +1 202 884 2120    Stefanie.Margulies@childrensnational.org   
Principal Investigator: Andrew Campbell         
United States, Florida
University of Florida College of Medicine Recruiting
Gainesville, Florida, United States, 32610
Contact: Mona Sayedul Huq    353-273-9120    monahuq@peds.ufl.edu   
Principal Investigator: Vandy Black         
Joe DiMaggio Childrens Hospital Recruiting
Hollywood, Florida, United States, 33021
Contact: Alejandra Smith    954-265-5324    alejsmith@mhs.net   
Principal Investigator: Anne Schaefer         
United States, Georgia
Childrens Healthcare of Atlanta Recruiting
Atlanta, Georgia, United States, 30342
Contact: Michele-Corinne Ako       Michele-Corinne.Ako@choa.org   
Principal Investigator: Robert Clark Brown         
United States, Illinois
Ann and Robert H Lurie Childrens Hospital of Chicago CTBM100C2407 Recruiting
Chicago, Illinois, United States, 60611
Contact: Zeinab Alward       zalward@luriechildrens.org   
Principal Investigator: Alexis Thompson         
University of Chicago Hospital Recruiting
Chicago, Illinois, United States, 60637
Contact    773-702-2084      
Principal Investigator: Radhika Peddinti         
United States, Massachusetts
Childrens Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Maud Muosieyiri    617-355-7700    Maud.Muosieyiri@childrens.harvard.edu   
Principal Investigator: Matthew M Heeney         
United States, New Jersey
Institute for Pediatric Cancer and Blood Disorders Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Elana Smilow    551-996-5437    elana.smilow@hackensackmeridian.org   
Principal Investigator: Stacey Rifkin-Zenenberg         
UMDNJ Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Sherri Gzemski       gzemsksa@rwjms.rutgers.edu   
Principal Investigator: Richard DRACHTMAN         
United States, New York
Children's Hospital at Montefiore Recruiting
Bronx, New York, United States, 10467
Contact: Jill Fillipelli    718-741-2384    jfilipelli@brany.com   
Principal Investigator: Deepa Manwani         
United States, North Carolina
Duke University Medical Center Oncology Recruiting
Durham, North Carolina, United States, 27710
Contact: Lindsay Lowe    919-684-1018    lindsay.lowe@duke.edu   
Principal Investigator: Jennifer Rothman         
East Carolina University SC Recruiting
Greenville, North Carolina, United States, 27834
Contact: Bree Williams    252-744-4676    williamsbree18@ecu.edu   
Principal Investigator: Beng Fuh         
United States, Pennsylvania
Childrens Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104 4399
Contact: Ella Ardoin    267-426-9338    ardoine@chop.edu   
Principal Investigator: Kim Smith Whitley         
United States, South Carolina
Medical University of South Carolina Medical Uni of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Linda M. Wozniak       Linda@dermandlaser.com   
Principal Investigator: Shayla Bergmann         
United States, Tennessee
St. Jude Children's Research Hosptial Recruiting
Memphis, Tennessee, United States, 38105
Contact: Olivia McGregor    901-595-7188    Olivia.McGregor@stjude.org   
Principal Investigator: Jeremie Heath Estepp         
United States, Texas
Cook Childrens Medical Center Oncology Recruiting
Fort Worth, Texas, United States, 76104
Contact: Lynn Davisson    682-885-1990    Lynn.Davisson@cookchildrens.org   
Principal Investigator: Clarissa Johnson         
Belgium
Novartis Investigative Site Recruiting
Edegem, Antwerpen, Belgium, 2650
Novartis Investigative Site Recruiting
Brussel, Belgium, 1000
Novartis Investigative Site Recruiting
Laeken, Belgium, 1020
Novartis Investigative Site Recruiting
Liege, Belgium, 4000
Brazil
Novartis Investigative Site Recruiting
Salvador, BA, Brazil, 41253-190
Novartis Investigative Site Recruiting
Ribeirao Preto, SP, Brazil, 14048-900
Canada, Quebec
Novartis Investigative Site Recruiting
Montreal, Quebec, Canada, H3T 1C5
Colombia
Novartis Investigative Site Recruiting
Medellin, Antioquia, Colombia, 05001000
Novartis Investigative Site Recruiting
Cali, Valle Del Cauca, Colombia
Novartis Investigative Site Recruiting
Monteria, Colombia
France
Novartis Investigative Site Recruiting
Paris cedex 15, France, 75015
Germany
Novartis Investigative Site Recruiting
Heidelberg, Baden Wuerttemberg, Germany, 69120
Novartis Investigative Site Recruiting
Berlin, Germany, 13353
India
Novartis Investigative Site Recruiting
Nagpur, Maharashtra, India, 440009
Novartis Investigative Site Recruiting
New Delhi, India, 110029
Novartis Investigative Site Recruiting
Vellore, India
Italy
Novartis Investigative Site Recruiting
Modena, Italy, 41124
Novartis Investigative Site Recruiting
Orbassano, Italy, 10043
Novartis Investigative Site Recruiting
Padova, Italy, 35128
Lebanon
Novartis Investigative Site Recruiting
Beirut, Lebanon, 1107 2020
Novartis Investigative Site Recruiting
Tripoli, Lebanon, 1434
Oman
Novartis Investigative Site Recruiting
Muscat, Oman, 123
Spain
Novartis Investigative Site Recruiting
Esplugues de Llobregat, Barcelona, Spain, 08950
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Valencia, Comunidad Valenciana, Spain, 46026
Novartis Investigative Site Recruiting
Palma De Mallorca, Islas Baleares, Spain, 07120
Novartis Investigative Site Recruiting
Madrid, Spain, 28007
Switzerland
Novartis Investigative Site Recruiting
Aarau, Aargau, Switzerland, 5001
Turkey
Novartis Investigative Site Recruiting
Adana, Turkey, 01330
Novartis Investigative Site Recruiting
Mersin, Turkey, 33343
United Kingdom
Novartis Investigative Site Recruiting
London, United Kingdom, SE5 8AD
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03474965    
Other Study ID Numbers: CSEG101B2201
2017-001747-12 ( EudraCT Number )
First Posted: March 23, 2018    Key Record Dates
Last Update Posted: August 14, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
SEG101
Sickle cell disease
SCD
crizanlizumab
pediatric
pharmacokinetic
P-selectin
Covid-19
Coronavirus disease 2019
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn