An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old (MACS2163)

• ClinicalTrials.gov Identifier: NCT01724138
• Recruitment Status: Withdrawn
• First Posted: November 9, 2012
• Last Update Posted: April 20, 2017
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: October 24, 2012
• First Posted Date: November 9, 2012
• Last Update Posted Date: April 20, 2017
• Study Start Date: June 2013
• Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 6, 2012)

• the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old. [ Time Frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. ]
  Area under the plasma concentration-time curve from time zero to the end of the dosing interval.
• the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Cmax [ Time Frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. ]
  The maximum plasma concentration of study medication.
• the PK profile of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old: Tmax [ Time Frame: PK sampling times are 0.5, 2.5, 6, 10h in Day 1 postdose; Day 2, 3, 4 and 5 predose and 0.5, 2.5, 6, 10h post dose on Day 4, then pre-dose at each subsequent visit until Week 49. Day -1 PK sample will be treated as Day 1 predose sample. ]
  Tmax was directly determined from the raw plasma concentration-time data.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 6, 2012)

• The safety and tolerability of deferasirox following multiple dosing in pediatric β-thalassemia major patients. [ Time Frame: Baseline, every 4 weeks until 48 weeks after taking the drug ]
  The adverse events and abnormal measurements of hematology, blood chemistry, urinalysis, urinary protein/creatinine ratio, physical examination, auditory and ocular examinations, ECG, ECHO, and growth development are collected for the measurement of safety and tolerability.
• The efficacy of deferasirox in pediatric β-thalassemia patients as measured by change of serum ferritin. [ Time Frame: Baseline, every 4 weeks until 48 weeks after taking the drug ]
  Changes in serum ferritin from baseline to every 4 weeks are collected for the measurement of efficacy.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old
• Official Title: An Open Label Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of Deferasirox Administered to Chinese Patients With β-thalassemia Major Aged From 2 to Less Than 6 Years Old
• Brief Summary: To characterize the PK of deferasirox in pediatric β-thalassemia major patients aged from 2 to less than 6 years old, when administrated with a fixed starting dose of 20 mg/kg/day.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: β-thalassemia Major

Intervention

Drug: Deferasirox

Patients will start their deferasirox treatment with a dose of 20 mg/kg/day.

Study Arms

Experimental: Deferasirox

The study will provide PK, safety, tolerability and efficacy data collected during 48 weeks of treatment with deferasirox in Chinese pediatric patients with transfusion dependent -thalassemia major, aged 2 to <6 years at enrollment. The target patient pool consists of 20 patients with evidence of iron overload measured by serum ferritin level at the start of study. Patients will start their deferasirox treatment with a dose of 20 mg/kg/day. Serum ferritin will be monitored every month and the dose of deferasirox will be adjusted if necessary every 3 months based on the trends in serum ferritin. Other possible dose adjustments will be based on the patient's safety assessments.

Intervention: Drug: Deferasirox

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: August 29, 2013): 0
• Original Estimated Enrollment (submitted: November 6, 2012): 20
• Estimated Study Completion Date: October 2014
• Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Pediatric patients aged from 2 to less than 6 years old.
• Patients with transfusion dependent β-thalassemia major.
• Serum ferritin values ≥ 1000 ng/ml at screening.
• Written informed consent must be obtained from the patient's legal guardian in accordance with local law and regulation prior to any screening procedures.

Exclusion Criteria:

• Non-transfusion-dependent thalassemia.
• Systemic diseases which would prevent study treatment (e.g. uncontrolled hypertension, cardiovascular, renal, hepatic, metabolic, etc.)
• Serum creatinine > age adjusted ULN.
• Significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥ 0.5mg/mg in a non-first void urine sample at screening. If UPCR is found to be ≥ 0.5 mg/mg the test can be repeated after 1 month.
• ALT/AST > 2.5xULN and total bilirubin > 1×ULN.
• Left ventricular ejection fraction < 56% by echocardiography.
• Patient has a known history of HIV seropositivity or history of active/treated hepatitis B or C (a test for screening is not required).
• A history of clinically relevant ocular and/or auditory toxicity related to iron chelation therapy
• Any surgical or medical conditions which will significantly alter the absorption, distribution, metabolism or excretion of the drug(e.g. ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or stomach and/or small bowel resection).
• Other conditions which investigator deems potential harm to patients if participate the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 71 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: China

Administrative Information

• NCT Number: NCT01724138
• Other Study ID Numbers: CICL670ACN02
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: August 2014