Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients (NCT03474965) | Clinical Trial Compass
CompletedPhase 2
Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients
United States117 participantsStarted 2018-10-01
Plain-language summary
The purpose of this study was to confirm and to establish appropriate dosing and to evaluate the safety in pediatric participants ages 2 to \<18 years with a history of Vaso-Occlusive Crisis (VOC) with or without Hydroxyurea/Hydroxycarbamide (HU/HC), receiving crizanlizumab for 2 years. The efficacy and safety of crizanlizumab was previously demonstrated in adults with sickle cell disease. The approach was to extrapolate from the pharmacokinetics (PK)/pharmacodynamics (PD) already established in the adult population. The study was designed as a Phase II, multicenter, open-label study.
Who can participate
Age range2 Years – 17 Years
SexALL
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Inclusion criteria
✓. Male or female patients ages 2 to \<18 years
✓. 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.
✓. 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
✓. 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, L-glutamine or erythropoietin stimulating agent during Part A are not allowed, and if this occurs, the participant will enter directly to Part B.
✓. Received standard age-appropriate care for SCD, including penicillin prophylaxis, pneumococcal immunization, and parental education.
✓. Performance status: Karnofsky ≥ 50% for patients \>10 years of age, and Lansky ≥ 50 for patients ≤ 10 years of age.
What they're measuring
1
Pharmacokinetics (PK): AUCd15 of Crizanlizumab After First Dose - Part A
Timeframe: Day 1 to Day 15
2
Pharmacokinetics (PK) - AUCtau for Serum Crizanlizumab After Multiple Doses - Part A - Steady State
Timeframe: Week 15 - Steady state
3
Pharmacokinetics (PK) - Cmax for Crizanlizumab After First Dose and Multiple Doses - Part A - Steady State
Timeframe: Week 1 (after first dose) and Week 15 (steady state)
4
Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab After First Dose - Part A - AUCd15
Timeframe: Day 1 to Day 15
5
Pharmacodynamics (PD) - P-selectin Inhibition Parameters for Crizanlizumab - Part A - AUCtau After Multiple Dose - Steady State
Timeframe: Week 15 - Steady state
6
Frequency of Any Adverse Events (AEs) as a Measure of Safety and Tolerability
Timeframe: Adverse events are reported from the first dose of study treatment until end of study treatment Week 103 plus 105 days post-treatment follow-up, up to a maximum timeframe of approximately 2 years and 3.25 months.
✓. 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
✓. 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,
Exclusion criteria
✕. History of stem cell transplant.
✕. Received any blood products within 30 days prior to Week 1 Day 1 dosing.
✕. 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.
✕. Patients with bleeding disorders
✕.Contraindication or hypersensitivity to any drug from similar class as study drug or to any excipients of the study drug formulation.
✕.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.
✕.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.
✕0.Pregnant females or females who have given birth within the past 90 days or who are breastfeeding.