Deferasirox BID (Twice a Day) in Transfusion Dependent Thalassemia Patients With Inadequate Response to High Doses
Primary Purpose
Focus on Transfusion Dependent Thalassemia Patients Who Are Inadequate Responders to Deferasirox > 35mg/kgQD
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Deferasirox
Sponsored by
About this trial
This is an interventional treatment trial for Focus on Transfusion Dependent Thalassemia Patients Who Are Inadequate Responders to Deferasirox > 35mg/kgQD focused on measuring Thalassemia
Eligibility Criteria
Inclusion Criteria:
- Written informed consent must be obtained prior to any screening procedures
- Male or female aged ≥ 2 years at screening
- Patients with transfusion dependent thalassemia
- Patients confirmed as inadequate- responders to deferasirox > 35 mg/kg QD and treated with QD for at least 6 months
- Regular transfusion indicated by a blood requirement ≥ 8 blood transfusions per year at screening
- Serum ferritin level > 2,500 ng/mL at screening (two consecutive values at least 2 weeks apart from each other)
- One SF measurement > 2,500 ng/mL between 6 and 9 months prior to study enrollment
- Three SF measurements > 2,500 ng/mL, performed at least 3 weeks apart from each other, during the 6 month treatment with QD dosing of deferasirox prior to study enrollment
- The average of the two screening SF values (collected 2 weeks apart from each other) must not show a decrease from the 6 to 9 month SF value taken prior to study enrollment
- The average of the two screening SF values (collected 2 weeks apart from each other) must not show a decrease from each of the three SF values obtained during the 6 months of deferasirox QD treatment prior to study enrollment
- LIC ≥ 7 mg Fe/g dw measured at the screening visit, (this value will be used as a baseline measurement
Exclusion Criteria:
- Patients who are intolerant to > 35 mg/kg/day QD of deferasirox in the 6 months prior to study enrollment
- Patients with mean levels of ALT >5 x ULN
- Patients with serum creatinine above the upper limit of normal (ULN)
- Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 (mg/mg)
- Creatinine clearance ≤ 60 ml/min
- Chronic hepatitis B infection, active hepatitis C infection
- History of a positive HIV test
- Uncontrolled systemic hypertension
- Patients participating in another clinical trial or receiving a systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days of screening
- History of non-compliance with medical regimens or patients who are considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol
- History of hypersensitivity to any of the study drug or excipients
- Significant medical condition interfering with the ability to partake in this study (e.g. systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic etc.)
- History of drug or alcohol abuse within the 12 months prior to enrollment.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Deferasirox
Arm Description
Deferasirox 20mg/kg taken BID
Outcomes
Primary Outcome Measures
Mean relative change in SF (Serum Ferritin)
To evaluate the efficacy of a twice-daily dose regimen of deferasirox in inadequate-responders to a once daily dose regimen as measured by relative change in serum ferritin from baseline to 24 weeks of treatment
Secondary Outcome Measures
Mean Absolute/relative change in LIC
To evaluate the efficacy of BID deferasirox in liver iron removal as measured by MRI by absolute/relative change from baseline to 24 weeks of treatment
Full Information
NCT ID
NCT01948817
First Posted
September 19, 2013
Last Updated
April 19, 2017
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01948817
Brief Title
Deferasirox BID (Twice a Day) in Transfusion Dependent Thalassemia Patients With Inadequate Response to High Doses
Official Title
A Prospective Single Arm Study to Assess the Efficacy and Safety of Deferasirox 20 mg/kg BID in Transfusion Dependent Thalassemia Patients Inadequately Responding to Current Treatment With Doses > 35mg/kg QD (Once a Day).
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Withdrawn
Study Start Date
February 2014 (undefined)
Primary Completion Date
February 2016 (Anticipated)
Study Completion Date
February 2016 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an open label, single arm, and multicenter study. The study will include the following phases. A screening phase which lasts for 4 weeks to determine patient eligibility. This phase will be followed by a 24 week Open label treatment phase. The study treatment is defined as deferasirox 20mg/kg BID 9Twice a day). Serum Ferritin Levels and MRI (Magmetic Resonance Imaging) LIC (Liver Iron Concentration) will be measured to evaluate the response to BID.
Detailed Description
Study treatment is defined as deferasirox 20 mg/kg BID. The study treatment duration is 24 weeks. After the baseline visit, patient visits will occur weekly during the first month because key safety parameters need to be performed weekly in the first month of treatment and then every 4 weeks thereafter until week 24 End of Treatment (EOT).
Patients will have their first dose of study treatment at Visit 3. Safety assessments are routinely performed including collection of AEs (Adverse Events), SAEs (Serious ADverse Events<, vital signs, physical examination, ECG (Electrocardiograph), hematological and biochemistry assessments.
Patients will continue therapy until intolerable toxicity, patient decision or after 24 weeks treatment duration at which point and End of Treatment (EOT) visit will be performed and the End of Treatment CRF( Case Report Form) will be completed.
30 day Safety follow-up Patients who discontinue study drug before completing the study should be scheduled for a visit as soon as possible, at which time all of the assessments listed for the final visit will be performed. At a minimum, all patients who discontinue study treatment, including those who refuse to return for a final visit, will be contacted for safety evaluations during the 30 days following the last dose of study drug.
All patients must be followed for AEs and SAEs that may have occurred after discontinuation from the study treatment. The safety follow-up visit will take place 30 days after the last dose of study drug.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Focus on Transfusion Dependent Thalassemia Patients Who Are Inadequate Responders to Deferasirox > 35mg/kgQD
Keywords
Thalassemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Deferasirox
Arm Type
Experimental
Arm Description
Deferasirox 20mg/kg taken BID
Intervention Type
Drug
Intervention Name(s)
Deferasirox
Intervention Description
Deferasirox 20mg/kg taken BID
Primary Outcome Measure Information:
Title
Mean relative change in SF (Serum Ferritin)
Description
To evaluate the efficacy of a twice-daily dose regimen of deferasirox in inadequate-responders to a once daily dose regimen as measured by relative change in serum ferritin from baseline to 24 weeks of treatment
Time Frame
Baseline, 24 Weeks
Secondary Outcome Measure Information:
Title
Mean Absolute/relative change in LIC
Description
To evaluate the efficacy of BID deferasirox in liver iron removal as measured by MRI by absolute/relative change from baseline to 24 weeks of treatment
Time Frame
Baseline, 24 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent must be obtained prior to any screening procedures
Male or female aged ≥ 2 years at screening
Patients with transfusion dependent thalassemia
Patients confirmed as inadequate- responders to deferasirox > 35 mg/kg QD and treated with QD for at least 6 months
Regular transfusion indicated by a blood requirement ≥ 8 blood transfusions per year at screening
Serum ferritin level > 2,500 ng/mL at screening (two consecutive values at least 2 weeks apart from each other)
One SF measurement > 2,500 ng/mL between 6 and 9 months prior to study enrollment
Three SF measurements > 2,500 ng/mL, performed at least 3 weeks apart from each other, during the 6 month treatment with QD dosing of deferasirox prior to study enrollment
The average of the two screening SF values (collected 2 weeks apart from each other) must not show a decrease from the 6 to 9 month SF value taken prior to study enrollment
The average of the two screening SF values (collected 2 weeks apart from each other) must not show a decrease from each of the three SF values obtained during the 6 months of deferasirox QD treatment prior to study enrollment
LIC ≥ 7 mg Fe/g dw measured at the screening visit, (this value will be used as a baseline measurement
Exclusion Criteria:
Patients who are intolerant to > 35 mg/kg/day QD of deferasirox in the 6 months prior to study enrollment
Patients with mean levels of ALT >5 x ULN
Patients with serum creatinine above the upper limit of normal (ULN)
Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 (mg/mg)
Creatinine clearance ≤ 60 ml/min
Chronic hepatitis B infection, active hepatitis C infection
History of a positive HIV test
Uncontrolled systemic hypertension
Patients participating in another clinical trial or receiving a systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days of screening
History of non-compliance with medical regimens or patients who are considered potentially unreliable and/or not cooperative, unwilling or unable to comply with the protocol
History of hypersensitivity to any of the study drug or excipients
Significant medical condition interfering with the ability to partake in this study (e.g. systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic etc.)
History of drug or alcohol abuse within the 12 months prior to enrollment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
Deferasirox BID (Twice a Day) in Transfusion Dependent Thalassemia Patients With Inadequate Response to High Doses
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