Efficacy and Safety Study of Deferasirox in Patients With Non-transfusion Dependent Thalassemia - Clinical Trial for Non-transfusion Dependent Thalassemia | NCT01709838

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Primary Purpose

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

deferasirox

About this trial

This is an interventional treatment trial for Non-transfusion Dependent Thalassemia focused on measuring Non-transfusion dependent thalassemia, NTDT, deferasirox, ICL670, LIC, Liver Iron Concentration

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Deferasirox

Arm Description

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

Outcomes

Primary Outcome Measures

Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline

Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment

Secondary Outcome Measures

Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw

The percentage of participants with baseline LIC>15 mg Fe/g dw achieving an LIC <5 mg Fe/g dw during the study

Time to Achieving LIC <5 mg Fe/g dw

Time to achieving LIC <5 mg Fe/g dw for participants with baseline LIC>15 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

Time from the target LIC <3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period

Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2)

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™)

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 Over Time

Absolute change in serum ferritin from baseline over time up to 260 weeks

Serum Ferritin (SF) vs LIC at Baseline and 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.

Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and 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 LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome

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)

Absolute Change in Serum Ferritin From Baseline After 52 Weeks

Absolute change in serum ferritin from baseline after 52 weeks of treatment

PK Parameters: AUCtau

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).

PK Parameters: Cmax

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

PK Parameters: Tmax

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

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.

Full Information

NCT ID

NCT01709838

First Posted

October 16, 2012

Last Updated

September 19, 2019

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01709838

Brief Title

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

Acronym

THETIS

Official Title

An Open Label, Multi-center, Efficacy and Safety Study of Deferasirox in Iron Overloaded Patients With Non-transfusion Dependent Thalassemia

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

December 6, 2012 (Actual)

Primary Completion Date

January 3, 2015 (Actual)

Study Completion Date

January 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-transfusion Dependent Thalassemia

Keywords

Non-transfusion dependent thalassemia, NTDT, deferasirox, ICL670, LIC, Liver Iron Concentration

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

134 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Deferasirox

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

deferasirox

Other Intervention Name(s)

ICL670

Intervention Description

Deferasirox dispersible tablets at strengths of 125 mg, 250 mg, and 500 mg were administered by oral daily dosing.

Primary Outcome Measure Information:

Title

Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline

Description

Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment

Time Frame

Baseline, 52 weeks

Secondary Outcome Measure Information:

Title

Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw

Description

The percentage of participants with baseline LIC>15 mg Fe/g dw achieving an LIC <5 mg Fe/g dw during the study

Time Frame

5 years

Title

Time to Achieving LIC <5 mg Fe/g dw

Description

Time to achieving LIC <5 mg Fe/g dw for participants with baseline LIC>15 mg Fe/g dw during the study

Time Frame

5 years

Title

Time From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period

Description

Time from the target LIC <3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period

Time Frame

post-baseline, up to 260 weeks

Title

Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2)

Description

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)].

Time Frame

Baseline, 52, 104 & 156 Weeks

Title

Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™)

Description

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)].

Time Frame

Baseline, 52, 104 & 156 Weeks

Title

Absolute Change in LIC From Baseline Over Time

Description

Absolute change in serum ferritin from baseline over time up to 260 weeks

Time Frame

24, 52, 76, 104, 128, 156, 180, 208, 232, 260 Weeks

Title

Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up)

Description

Correlation between serum ferritin and LIC is assessed using scatter plots with pearson correlation coefficient and simple linear model.

Time Frame

Baseline, End of Study (EOS): Week 260 + 30 days follow up

Title

Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up)

Description

Correlation for absolute change between LIC and serum ferritin was assessed using scatter plots with pearson correlation coefficient and simple linear model.

Time Frame

Week 24, End of Study (EOS): Week 260 + 30 days follow up

Title

Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome

Description

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)

Time Frame

Baseline, 52 Weeks

Title

Absolute Change in Serum Ferritin From Baseline After 52 Weeks

Description

Absolute change in serum ferritin from baseline after 52 weeks of treatment

Time Frame

Baseline, 52 weeks

Title

PK Parameters: AUCtau

Description

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).

Time Frame

pre-dose (0 hour), and at 2, and 4 hours at Week 4

Title

PK Parameters: Cmax

Description

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

Time Frame

pre-dose (0 hour), and at 2, and 4 hours at Week 4

Title

PK Parameters: Tmax

Description

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.

Time Frame

pre-dose (0 hour), and at 2, and 4 hours at Week 4

Title

Plasma Pharmacokinetics (PK) Deferasirox Concentrations

Description

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.

Time Frame

Weeks 12 & 24: pre-dose (0hr), 2hr & 4hr post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Nanning

State/Province

Guangxi

ZIP/Postal Code

530021

Country

China

Facility Name

Novartis Investigative Site

City

Goudi-Athens

State/Province

GR

ZIP/Postal Code

115 27

Country

Greece

Facility Name

Novartis Investigative Site

City

Cagliari

State/Province

CA

ZIP/Postal Code

09121

Country

Italy

Facility Name

Novartis Investigative Site

City

Milano

State/Province

MI

ZIP/Postal Code

20122

Country

Italy

Facility Name

Novartis Investigative Site

City

Hazmiyeh

State/Province

Beirut

ZIP/Postal Code

PO BOX 213

Country

Lebanon

Facility Name

Novartis Investigative Site

City

Bangkok

ZIP/Postal Code

10700

Country

Thailand

Facility Name

Novartis Investigative Site

City

Tunis

ZIP/Postal Code

1006

Country

Tunisia

Facility Name

Novartis Investigative Site

City

Adana

ZIP/Postal Code

01330

Country

Turkey

Facility Name

Novartis Investigative Site

City

Istanbul

ZIP/Postal Code

34093

Country

Turkey

Facility Name

Novartis Investigative Site

City

Izmir

ZIP/Postal Code

35040

Country

Turkey

Facility Name

Novartis Investigative Site

City

London

ZIP/Postal Code

NW1 2PJ

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

IPD Sharing URL

https://www.clinicalstudydatarequest.com

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

Non-transfusion Dependent Thalassemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial