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Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients

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ClinicalTrials.gov Identifier: NCT03474965
Recruitment Status : Recruiting
First Posted : March 23, 2018
Last Update Posted : August 26, 2019
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 patients 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 Drug: Crizanlizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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 : December 31, 2020
Estimated Study Completion Date : August 22, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Crizanlizumab
SEG101 (crizanlizumab) drug administered at a dose of 5.0 mg/kg on Week 1 Day 1, Week 3 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 patients aged 2 to < 18 years (Parts A)

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

  3. PK (AUCtau) after 5th dose [ Time Frame: Week 15 ]
    Confirm appropriate dosing of Crizanlizumab in patients aged 2 to < 18 years old

  4. PD (AUCtau) after 5th dose [ Time Frame: Week 15 ]
    Confirm appropriate dosing of Crizanlizumab in patients aged 2 to < 18 years old

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

  6. PK pre-dose concentrations [ Time Frame: Week 3 to Week 19 ]
    Confirm appropriate dosing of crizanlizumab in patients 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 patients aged 6 months to < 18 years (Parts A and B)


Secondary Outcome Measures :
  1. Number of 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 patients at the time of study entry (Parts A and B)

  2. Number of 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 patients at the time of study entry (Parts A and B)

  3. Number of 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 patients at the time of study entry (Parts A and B)

  4. Number of 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 patients at the time of study entry (Parts A and B)

  5. Number of 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 patients at the time of study entry (Parts A and B)

  6. Number of dactylitis events [ Time Frame: 6 months, 2 years ]
    To assess the long-term efficacy of crizanlizumab in 6 months to < 18 year old patients 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 patients 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 patients 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 patients 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 patients 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 patients 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 patients aged 6 months to >18 years

  13. PD 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 patients aged 6 months to >18 years

  14. 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 patients 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

Eligibility Criteria: Inclusion Criteria:

  • Male or female patients aged 2 to <18 years (Group 3 will be expanded to allow enrolment of patients aged 6 to <24 months (and at least 6 kg) in Part B once the appropriate dose is confirmed in 2 to <6 year old patients)
  • Confirmed diagnosis of sickle cell disease (SCD) (e.g. any genotype including HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia, and others) by hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) performed locally.
  • Experienced at least 1 VOC within the preceding 12 months, as determined by medical history. Prior VOC must have resolved at least 7 days prior to the first dose in the study and should include all the following:

    1. the occurrence of appropriate symptoms (see VOC definition in protocol Section 7.2.1.1)
    2. either a visit to a medical facility or healthcare professional,
    3. receipt of oral/parenteral opioid or other non-opioid parenteral analgesia.
  • If receiving HU/HC or erythropoietin stimulating agent, must have been receiving the drug for at least 6 months prior to Screening and plan to continue taking at the same dose and schedule during the trial. Dose alterations of HU/HC during Part A are not allowed, and if this occurs, the patient will enter directly to the Part B.
  • Received standard age-appropriate care for SCD, including penicillin prophylaxis, pneumococcal immunization, and parental education
  • Transcranial Doppler (TCD) considered low risk within the past 6 months (for 2 to 16 years).

Exclusion Criteria:

  • History of stem cell transplant.
  • Received any blood products within 30 days of Day 1 dosing.
  • Participating in a chronic transfusion program (preplanned series of transfusions for prophylactic purposes).
  • Patients with bleeding disorders
  • Planning on undergoing an exchange transfusion during the duration of the study. Patients requiring episodic transfusion in response to worsened anemia or VOC are permitted.
  • Contraindication or hypersensitivity to any drug from similar class as study drug or to any excipients of the study drug formulation.
  • Received a monoclonal antibody or immunoglobulin-based therapy within 6 months of Screening, or has documented immunogenicity to a prior monoclonal antibody.
  • 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.
  • Pregnant females or females who have given birth within the past 90 days or who are breastfeeding.
  • Any documented history of a stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months
  • Any conditional TCD within the past 12 months
  • Use of therapeutic anticoagulation (prophylactic doses permitted) or antiplatelet therapy (other than aspirin) within the 10 days prior to Week 1 Day 1 dosing
  • Hospitalized at Screening
  • Planning to undergo a major surgical procedure during the duration of the study
  • Planning to initiate or terminate HU/HC while on study, other than for safety reasons
  • Patient with active HIV infection (detectable viral load)
  • Patients with known active Hepatitis B infection.
  • Patients with known Hepatitis C history.
  • Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator.
  • 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.
  • Has a serious mental or physical illness, which, in the opinion of the Investigator would compromise participation in the study.
  • 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.
  • Cardiac or cardiac repolarization abnormality
  • Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome
  • Sexually active females who are unwilling to comply with reliable method of birth control until 15 weeks following last dose of study drug.
  • Current drug or alcohol abuse:

    1. Has a positive qualitative urine drug test at Screening for cocaine, phencyclidine (PCP), or amphetamines (opioids are permitted).
    2. Consumes >12 (for males) or >8 (for females) standard alcoholic beverages per week.
  • Not able to understand and to comply with study instructions and requirements.
  • Subjects, who are an employee of the sponsor or investigator or otherwise dependent on them.
  • Subjects, who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.

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

  Show 29 Study Locations
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     History of Changes
Other Study ID Numbers: CSEG101B2201
2017-001747-12 ( EudraCT Number )
First Posted: March 23, 2018    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019
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
crizanlizumab
pediatric
pharmacokinetic
P-selectin
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn