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
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.
6 Months to 17 Years
Accepting Healthy Volunteers?
- 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 188.8.131.52)
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).
- 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.