Efficacy and Safety Study of Deferasirox in Patients With Non-transfusion Dependent Thalassemia

Phase 4

Completed

• Conditions: Non-transfusion Dependent Thalassemia
• Interventions: Drug: deferasirox

• Registration Number: NCT01709838
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

Assessed the efficacy of deferasirox in patients with non-transfusion dependent thalassemia based on change in liver iron concentration from baseline after 52 weeks of treatment. Provided further assessment of the long-term efficacy and safety of deferasirox in NTDT patients with iron overload (LIC ≥ 5 mg Fe/g liver dw and SF ≥ 300 ng/mL) for up to 260 weeks.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-10-16
• Study First Submitted QC: 2012-10-17
• Study First Posted: 2012-10-18
• Study Start: 2012-12-06
• Primary Completion: 2015-01-03
• Study Completion: 2019-01-17
• Results First Submitted: 2019-07-17
• Results First Submitted QC: 2019-07-17
• Results First Posted: 2019-08-28
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-19
• Last Update Posted: 2019-10-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 134

Inclusion Criteria

Non-transfusion dependent congenital or chronic anemia inclusive of beta-thalassemia intermedia, HbE beta-thalassemia or alpha-thalassemia intermedia (HbH disease)/ Liver iron concentration >/= 5 mg Fe/g dw Serum Ferritin >/= 300 ng/mL

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Exclusion Criteria

HbS-beta Thalassemia, anticipated regular transfusion program during the study, blood transfusion 6 months prior to study start, significant proteinuria, creatinine clearance </= 40 ml/min, serum creatinine > ULN, ALT >5 x ULN, active hepatitis B or C, cirrhosis

Pediatrics Only:

A patient's weight of at least 20 kg is required to allow dosing of 5 mg/kg with one tablet of 125 mg

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Deferasirox	deferasirox	All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).

Primary Outcome Measures

Name	Time	Method
Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline	Baseline, 52 weeks	Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Absolute Change in LIC From Baseline Over Time	24, 52, 76, 104, 128, 156, 180, 208, 232, 260 Weeks	Absolute change in serum ferritin from baseline over time up to 260 weeks
PK Parameters: AUCtau	pre-dose (0 hour), and at 2, and 4 hours at Week 4	The pharmacokinetic parameter, AUCtau was determined using non-compartmental method(s) for deferasirox and its iron complex. AUC=area under the concentration-time curve during a dosing interval at steady state (amount × time × volume).
Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw	5 years	The percentage of participants with baseline LIC\>15 mg Fe/g dw achieving an LIC \<5 mg Fe/g dw during the study
Time From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period	post-baseline, up to 260 weeks	Time from the target LIC \<3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period
Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up)	Baseline, End of Study (EOS): Week 260 + 30 days follow up	Correlation between serum ferritin and LIC is assessed using scatter plots with pearson correlation coefficient and simple linear model.
PK Parameters: Tmax	pre-dose (0 hour), and at 2, and 4 hours at Week 4	The pharmacokinetic parameter, Tmax, may be determined using non-compartmental method(s) for deferasirox and its iron complex. Tmax=time to reach maximum/peak concentration following drug administration.
Plasma Pharmacokinetics (PK) Deferasirox Concentrations	Weeks 12 & 24: pre-dose (0hr), 2hr & 4hr post-dose	Blood samples for PK evaluation were collected for a sub-group of patients. The patient had to have been on treatment without dose adjustment or treatment interruption (for any reason) for at least 4 consecutive days prior to scheduled PK sampling visit. If there was a dosage change or interruption within 4 days of the visit, no PK blood samples was collected, and an appropriate comment had to be made on the PK CRF page.
Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up)	Week 24, End of Study (EOS): Week 260 + 30 days follow up	Correlation for absolute change between LIC and serum ferritin was assessed using scatter plots with pearson correlation coefficient and simple linear model.
Absolute Change in Serum Ferritin From Baseline After 52 Weeks	Baseline, 52 weeks	Absolute change in serum ferritin from baseline after 52 weeks of treatment
Time to Achieving LIC <5 mg Fe/g dw	5 years	Time to achieving LIC \<5 mg Fe/g dw for participants with baseline LIC\>15 mg Fe/g dw during the study
Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2)	Baseline, 52, 104 & 156 Weeks	The SF-36 is a self-administered questionnaire for adults (from 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, General health perceptions, Vitality, Social functioning, Role limitations due to emotional problems and General mental health . The higher values indicate a better evaluation of health. Range: 0 to 100 \[0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)\].
Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™)	Baseline, 52, 104 & 156 Weeks	The PedsQL™ is a modular approach to measuring health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL™ Generic Core Scales encompass the essential core domains for pediatric HRQOL measurement: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). The Generic Core Scales are designed to enable comparisons across patient and healthy populations. The higher values indicate a better evaluation of health. Range: 0 to 100 \[0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)\].
Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome	Baseline, 52 Weeks	Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment by underlying NTDT syndrome. The 4 underlying disease types: Beta-thalassemia intermedia (N =69), HbE beta-thalassemia (N = 24), Alpha-thalassemia intermedia (HbH disease) (N = 40), Other, specify (N = 1)
PK Parameters: Cmax	pre-dose (0 hour), and at 2, and 4 hours at Week 4	The pharmacokinetic parameter, Cmax, was determined using non-compartmental method(s) for deferasirox and its iron complex. Cmax (maximum/peak plasma drug concentration after drug administration)=amount × volume

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 London, United Kingdom