A Study of Dose Confirmation and Safety of Experimental Crizanlizumab for Pediatric Sickle Cell Disease
a study on Sickle Cell Anemia
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.
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
Sickle Cell Disease SEG101 crizanlizumab pediatric pharmacokinetic P-selectin Anemia, Sickle Cell
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 184.108.40.206)
- 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).
- 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.
- 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 at UC Davis
- Jo Chung
Associate Professor, General Pediatrics. Authored (or co-authored) 6 research publications
Please contact me about this study
We will not share your information with anyone other than the team in charge of this study. Submitting your contact information does not obligate you to participate in research.
The study team should get back to you in a few business days.