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Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia (CENTAurus)

Primary Purpose

Thalassemia (Transfusion Delendent)

Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
deferasirox
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Thalassemia (Transfusion Delendent) focused on measuring Endocrine complications, transfusion dependent thalassemia

Eligibility Criteria

2 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

1. Beta thalassemia major and severe intermedia patients transfusion dependent and with transfusional iron overload 2. Patients with diagnosis of impaired fasting glucose or impaired glucose tolerance 4.Patients naïve to deferasirox or patients who already receive deferasirox at sub-optimal doses 5.Cardiac MRI T2* >10 msec; 7.normal cardiac function (LVEF > 56%);

Exclusion Criteria:

  1. Non transfusional hemosiderosis;
  2. Patients with diabetes mellitus (genetic or secondary) or history of diabetes mellitus in 1st degree relatives;

4.Patients who received organ transplant; 5.Patients with galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption; 6.Patients unable to tolerate (or who have unacceptable toxicities to) prior treatment with deferasirox; 7.History of hypersensitivity to the study drug or any of its excipients; 8. Renal impairment 10. Liver impairment; 11.Patients with active chronic hepatitis B infection, active hepatitis C infection;

Other protocol-defined inclusion/exclusion criteria may apply" at the end

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    deferasirox

    Arm Description

    single arm. all patients will receive deferasirox

    Outcomes

    Primary Outcome Measures

    Change from baseline of glucose blood level measured after 2 h after receiving a glucose-equivalent oral challenge
    The primary efficacy variable is the change (mg/dl) from baseline to 36 months of glucose plasma levels measured 2 hr post glusose equivalent oral challange. After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of plasma glucose. This will be repeated every 6 month till end of study

    Secondary Outcome Measures

    Glucose of OGTT ( AUC)
    change in of glucose metabolism during deferasirox treatment measuring the change versus baseline of 2-hr and fasting glucose plasma level of OGTT.After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of plasma glucose . This will be repeated every 6 months till end of study
    change on insulin secretion and sensitivity
    Change in insulin secretion and insulin sensitivity at every measurement versus screening. Stumvol Formula will be applied to values of 2hr glucose OCTT to calucolate insulin secretion and insulin sensitivity. After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of insulin concentration.
    Measurement of thyroid hormones TSH and FT4
    Changes in plasma levels of TSH and FT4 at every measurement versus screening. Blood samples will be drawn from the patient at baseline and every 12 month till end of study and plansa concentration of thyroid hormons TSH and FT4 will be assessed.
    Risk factors for the impairment of glucose homeostasis
    information on age, sex, ethnicity, BMI, metabolic syndrome (hypertension, dyslipidemia, hypertrygliceridemia), chronic use of steroids, use of immunosuppressive drugs, growth hormonal deficit will be collected on a monthly basis till end of study
    Changes in endocrine funcionts parameters
    - Female patients will be assessed for the presence or absence of menses every month versus baseline .Use of current hormonal replacing therapy, if any (e.g. thyroxin therapy for patients with non-compensated hypothyroidism, hormonal replacement drugs for hypogonadal patients) will be checked on a monthly basis versus baseline
    Changes in parameters of bone metabolism
    - Blood samples wiil be drawn to measure levels of serum calcium, phosphorus, alkaline phosphatase, vitamin D levels (25-hydroxycholecalciferol), serum calcium, parathormone (intact 1-84 PTH) from baseline to the end of study. Blood samples will be drawn to assess also Vitamin D and parathormone at baseline and then every six months. The intact parathormone will be assessed by evaluating the 1-84 PTH form. Inorganic phosphorus, serum calcium will be assessed at baseline and then monthly; alkaline phosphatase will be evaluated at baseline, every two weeks during the first month of treatment and monthly thereafter till EOS.
    Iron overload status
    Blood samples will be drawn to assess Serum Ferriting. Liver and cardiac iron will be assessed by MRI (MRI R2 annual measurements for liver, MRI T2* annual measurements for cardiac); -Relationship between changes in SF, LIC and cardiac T2* and changes in primary (OGTT) and secondary endpoints (glucose metabolism trend, insulin secretion and insulin sensitivity);
    Safety of deferasirox therapy
    Clinical and laboratory monitoring of AEs and SAEs (in particular changes in hepatic, renal, audiometric and ophthalmology parameters). Blood samples will be drawn to assess liver functions, renal funtions. Urine test will be performed to assess renal functions. An audiometric and ophalmologic visit will be done to assess eyes and ears functions.

    Full Information

    First Posted
    February 20, 2014
    Last Updated
    April 19, 2017
    Sponsor
    Novartis Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02069886
    Brief Title
    Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia
    Acronym
    CENTAurus
    Official Title
    A Multicenter, Open-label, Single Arm, Interventional Phase IV Study, to Evaluate the Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2015
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    December 2014 (undefined)
    Primary Completion Date
    December 2018 (Anticipated)
    Study Completion Date
    December 2018 (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
    The CENTAurus trial is a prospective clinical study designed to address systematically some of the relevant endocrine complications in an iron overloaded thalassemic population, primary objective being the assessment of the effect of deferasirox therapy on glucose metabolism/homeostasis. Other endocrine parameters complementary or supportive to the primary objective will be assessed and analyzed during this study. A number of lab parameters related to other axes of the endocrine system will be collected and analyzed.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Thalassemia (Transfusion Delendent)
    Keywords
    Endocrine complications, transfusion dependent thalassemia

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Phase 4
    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
    single arm. all patients will receive deferasirox
    Intervention Type
    Drug
    Intervention Name(s)
    deferasirox
    Intervention Description
    125, 250, 500 mg dispersable tablets
    Primary Outcome Measure Information:
    Title
    Change from baseline of glucose blood level measured after 2 h after receiving a glucose-equivalent oral challenge
    Description
    The primary efficacy variable is the change (mg/dl) from baseline to 36 months of glucose plasma levels measured 2 hr post glusose equivalent oral challange. After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of plasma glucose. This will be repeated every 6 month till end of study
    Time Frame
    36 months
    Secondary Outcome Measure Information:
    Title
    Glucose of OGTT ( AUC)
    Description
    change in of glucose metabolism during deferasirox treatment measuring the change versus baseline of 2-hr and fasting glucose plasma level of OGTT.After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of plasma glucose . This will be repeated every 6 months till end of study
    Time Frame
    baseline and every 6 months measurement of 2hour Glocose of OGTT
    Title
    change on insulin secretion and sensitivity
    Description
    Change in insulin secretion and insulin sensitivity at every measurement versus screening. Stumvol Formula will be applied to values of 2hr glucose OCTT to calucolate insulin secretion and insulin sensitivity. After a 12-hour overnight fasting, at zero time (baseline) blood sample will be drawn and afterwards patients will receive a glucose-equivalent oral challenge (75 grams). After glucose loading plasma samples will be drawn at 30, 60, 90, 120 minutes for determination of insulin concentration.
    Time Frame
    baseline and every 6 months measurement of 2hr Glucose OGTT
    Title
    Measurement of thyroid hormones TSH and FT4
    Description
    Changes in plasma levels of TSH and FT4 at every measurement versus screening. Blood samples will be drawn from the patient at baseline and every 12 month till end of study and plansa concentration of thyroid hormons TSH and FT4 will be assessed.
    Time Frame
    baseline and every 12 months
    Title
    Risk factors for the impairment of glucose homeostasis
    Description
    information on age, sex, ethnicity, BMI, metabolic syndrome (hypertension, dyslipidemia, hypertrygliceridemia), chronic use of steroids, use of immunosuppressive drugs, growth hormonal deficit will be collected on a monthly basis till end of study
    Time Frame
    baseline and monthly till End of Study
    Title
    Changes in endocrine funcionts parameters
    Description
    - Female patients will be assessed for the presence or absence of menses every month versus baseline .Use of current hormonal replacing therapy, if any (e.g. thyroxin therapy for patients with non-compensated hypothyroidism, hormonal replacement drugs for hypogonadal patients) will be checked on a monthly basis versus baseline
    Time Frame
    baseline and monthly till EOS
    Title
    Changes in parameters of bone metabolism
    Description
    - Blood samples wiil be drawn to measure levels of serum calcium, phosphorus, alkaline phosphatase, vitamin D levels (25-hydroxycholecalciferol), serum calcium, parathormone (intact 1-84 PTH) from baseline to the end of study. Blood samples will be drawn to assess also Vitamin D and parathormone at baseline and then every six months. The intact parathormone will be assessed by evaluating the 1-84 PTH form. Inorganic phosphorus, serum calcium will be assessed at baseline and then monthly; alkaline phosphatase will be evaluated at baseline, every two weeks during the first month of treatment and monthly thereafter till EOS.
    Time Frame
    baseline, monthly or every 6 months till end of study
    Title
    Iron overload status
    Description
    Blood samples will be drawn to assess Serum Ferriting. Liver and cardiac iron will be assessed by MRI (MRI R2 annual measurements for liver, MRI T2* annual measurements for cardiac); -Relationship between changes in SF, LIC and cardiac T2* and changes in primary (OGTT) and secondary endpoints (glucose metabolism trend, insulin secretion and insulin sensitivity);
    Time Frame
    baseline and regularly till end of study (monthly or yearly as specified)
    Title
    Safety of deferasirox therapy
    Description
    Clinical and laboratory monitoring of AEs and SAEs (in particular changes in hepatic, renal, audiometric and ophthalmology parameters). Blood samples will be drawn to assess liver functions, renal funtions. Urine test will be performed to assess renal functions. An audiometric and ophalmologic visit will be done to assess eyes and ears functions.
    Time Frame
    baseline and at every scheduled visit (weekly for the first months or after dose escalation and monthly thereafter or yearly till EOS

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    2 Years
    Maximum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 1. Beta thalassemia major and severe intermedia patients transfusion dependent and with transfusional iron overload 2. Patients with diagnosis of impaired fasting glucose or impaired glucose tolerance 4.Patients naïve to deferasirox or patients who already receive deferasirox at sub-optimal doses 5.Cardiac MRI T2* >10 msec; 7.normal cardiac function (LVEF > 56%); Exclusion Criteria: Non transfusional hemosiderosis; Patients with diabetes mellitus (genetic or secondary) or history of diabetes mellitus in 1st degree relatives; 4.Patients who received organ transplant; 5.Patients with galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption; 6.Patients unable to tolerate (or who have unacceptable toxicities to) prior treatment with deferasirox; 7.History of hypersensitivity to the study drug or any of its excipients; 8. Renal impairment 10. Liver impairment; 11.Patients with active chronic hepatitis B infection, active hepatitis C infection; Other protocol-defined inclusion/exclusion criteria may apply" at the end
    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

    Effect of Deferasirox on Endocrine Complications in Subjects With Transfusion Dependent Thalassemia

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