Summary

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

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) (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:
  • 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 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:
  • 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.

Locations

  • UC Davis Medical Center accepting new patients
    Sacramento California 95817 United States
  • Phoenix Childrens Hospital CVAL489A2302 accepting new patients
    Phoenix Arizona 85016 United States

Lead Scientist

  • Jo Chung
    Associate Professor, General Pediatrics. Authored (or co-authored) 6 research publications

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