Study of Dose Confirmation and Safety of Crizanlizumab in Pediatric Sickle Cell Disease Patients
- Conditions
- Health Condition 1: D758- Other specified diseases of bloodand blood-forming organs
- Registration Number
- CTRI/2019/04/018555
- Lead Sponsor
- ovartis Healthcare Pvt Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
1. Male or female patients ages 2 to <18 years (Group 3 will be expanded to allow enrolment of patients ages 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)
2. Confirmed diagnosis of SCD (e.g. any genotype including HbSS, HbSC, HbSß0 thalassemia,HbSß+-thalassemia patients, others) by hemoglobin electrophoresis or highperformance
liquid chromatography (HPLC) [performed locally].
3. 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:
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 other non-opioid parenteral analgesia.
4. 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.
5. Received standard age-appropriate care for SCD, including penicillin prophylaxis,
pneumococcal immunization, and parental education
6. Performance status: Karnofsky = 50% for patients >10 years of age, and Lansky = 50 for
patients = 10 years of age
7. Patient must meet the following laboratory values at the screening visit:
? Absolute Neutrophil Count =1.0 x 109/L
? Platelets =75 x 109/L
? Hemoglobin (Hgb) > 5.5 g/dL
8. Patient must have adequate renal and hepatic function as defined:
? Estimated Glomerular filtration rate (eGFRe) = 45 mL/min/1.73 m2 using Schwartz
formula
? Direct (conjugated) bilirubin = 2.0 x ULN
? Alanine transaminase (ALT) = 3.0 x ULN
9. Transcranial Doppler (TCD) considered low risk within the past 6 months (for ages 2 to
16 years).
10. Written informed consent/assent, according to local guidelines, signed by the patients and
/ or by the parents or legal guardian prior to any study related screening procedures are
performed
11. Female of non-childbearing potential or with negative serum pregnancy test on Screening
and a negative urine pregnancy test (dipstick) prior to dosing on Day 1
•History of stem cell transplant.
•Received any blood products within 30 days of Day 1 dosing.
•Participating and maintaining 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.
•Planning to initiate or terminate HU/HC while on study, other than for safety reasons
•Significant active infection or immune deficiency (including chronic use of immunosuppressive drugs) in the opinion of the investigator.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1.PK (AUCd15) after 1st dose <br/ ><br>2.PD (AUCd15) after 1st dose <br/ ><br>3.PK (AUCtau) after 5th dose <br/ ><br>4.PK (AUCtau) after 5th dose <br/ ><br>5.PK (Cmax) after 1st dose and 5th dose <br/ ><br>6.PK pre-dose concentrations <br/ ><br>7.Frequency of any adverse events (AEs) as a measure of safety and tolerabilityTimepoint: 1.Time Frame: Day 15 <br/ ><br>2.Time Frame: Day 15 <br/ ><br>3.Time Frame: Week 15 <br/ ><br>4.Time Frame: Week 15 <br/ ><br>5.Time Frame: Week 1 and Week 15 <br/ ><br>6.Time Frame: Week 3 to Week 19 <br/ ><br>7.Time Frame: 6 months, 2 years
- Secondary Outcome Measures
Name Time Method