Summary

for people ages 6 months to 17 years (full criteria)
at Sacramento, California and other locations
study started
estimated completion

Description

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.

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

Keywords

Sickle Cell Disease SEG101 crizanlizumab pediatric pharmacokinetic P-selectin Anemia, Sickle Cell

Eligibility

For people ages 6 months to 17 years

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) (any genotype including HbSS, HbSC, HbSβ0-thalassemia, HbSβ+-thalassemia, and others) by hemoglobin electrophoresis and/or high-performance liquid chromatography (HPLC) performed locally. Confirmation of diagnosis by two accepted methods is recomended.
  • 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 should include all the following:
  • the occurrence of appropriate symptoms (see VOC definition in protocol Section 7.2.1.1)
  • either a visit to a medical facility or healthcare professional,
  • receipt of oral/parenteral opioid or parenteral NSAIDs.
  • 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 for at least 6 months prior to screening. 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) for patients aged 2 to <16 years with HbSS, HbSβ0-thalassemia, and HbSD disease indicating low risk for stroke (per investigator). Please refer to Section 7.2.2.6 for details

Exclusion Criteria:

  • History of stem cell transplant.
  • Received any blood products within 30 days prior to Day 1 dosing.
  • Plan to participate in a chronic transfusion program (preplanned 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.
  • Patients with bleeding disorders
  • Criterion no longer required (merged with criterion #3), removed as part of Amendment 2: 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 clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months. Silent infarcts (only present on imaging) are not excluded
  • Any abnormal 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 within 7 days prior to Week 1 Day 1 dosing.
  • Planning to undergo a major surgical procedure during the duration of the study
  • Planning to initiate or terminate HU/HC or L-glutamine 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.
  • Criterion no longer required, removed as part of Amendment 2: Current drug or alcohol abuse:
  • Has a positive qualitative urine drug test at Screening for cocaine, phencyclidine (PCP), or amphetamines (opioids are permitted).
  • 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.
  • Patients who received prior crizanlizumab treatment are not allowed.

Locations

  • Novartis Investigative Site accepting new patients
    Sacramento California 95817 United States
  • Novartis Investigative Site accepting new patients
    Phoenix Arizona 85016 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
Links
Sign up for this study
ID
NCT03474965
Phase
Phase 2
Study Type
Interventional
Last Updated