Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 7 of 22 for:    "Hemosiderosis" | "Iron Chelating Agents"

Extension Study of the Efficacy and Safety of Deferasirox Treatment in Beta-thalassemia Patients With Transfusional Hemosiderosis (Study Amended to 2-year Duration) (ESCALATOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00171301
Recruitment Status : Completed
First Posted : September 15, 2005
Results First Posted : July 29, 2011
Last Update Posted : August 31, 2011
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Beta-thalassemia Major
Hemosiderosis
Iron Overload
Rare Anemia
Intervention Drug: Deferasirox
Enrollment 233
Recruitment Details This is an Extension to Core Study CICL670A2402 (NCT00171171). 233 participants completed the core study and entered this extension study.
Pre-assignment Details 2 participants from the 16 and older group did not receive deferasirox. Thus, the 16 and older group comprises of 69 treated participants.
Arm/Group Title Deferasirox (Between 2 <16 Years ) Deferasirox (16 Years or Older)
Hide Arm/Group Description Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient’s body weight. Participants age 16 years or older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient’s body weight.
Period Title: Overall Study
Started 162 71 [1]
Received Deferasirox 162 69
Completed 154 62
Not Completed 8 9
Reason Not Completed
Death             1             2
Adverse Event             1             2
Lost to Follow-up             6             2
Protocol Violation             0             2
Withdrawal by Subject             0             1
[1]
2 participants in this group never received deferasirox.
Arm/Group Title Deferasirox (Between 2 <16 Years ) Deferasirox (16 Years or Older) Total
Hide Arm/Group Description Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient’s body weight. Participants age 16 years or older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient’s body weight. Total of all reporting groups
Overall Number of Baseline Participants 162 71 233
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 162 participants 71 participants 233 participants
9.5  (3.59) 21.2  (5.82) 13.0  (6.93)
[1]
Measure Description: Safety Population consisting of all participants who received study drug in the Extension study n= 231.
Sex/Gender, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 162 participants 71 participants 233 participants
Female 80 35 115
Male 82 36 118
[1]
Measure Description: Safety Population consisting of all participants who received study drug in the Extension study n=231.
1.Primary Outcome
Title Percentage of Participants With Treatment Success From Core Baseline (BL) to Extension End of Study, by Baseline LIC Level and Age
Hide Description Success was defined as the percentage of participants with decreased liver iron content (LIC) at the end of extension study compared to core baseline (BL) LIC. Success Criteria: For participants with Baseline LIC from 1 - <7 mg Fe/g dw, success was achieved if LIC level maintained at 1 - <7 mg Fe/g dw. For participants with Baseline LIC ≥7 - <10 mg Fe/g dw, success was achieved if LIC dropped to between 1 and < 7 mg Fe/g dw. For participants with Baseline LIC ≥10 mg Fe/g dw, success was achieved if LIC dropped by at least 3 mg Fe/g dw. LIC was measured by biopsy or magnetic resonance imaging.
Time Frame From Core Study Baseline, to Extension End of Study, Up to 3 Years
Hide Outcome Measure Data
Hide Analysis Population Description
The primary analysis will be on the intent-to-treat (ITT) population. ITT population includes all participants who performed the core end of study (EOS) visit evaluation and assessments and were included in the extension study. “n” is the number of participants analyzed in each category.
Arm/Group Title Deferasirox (Between 2 <16 Years) Deferasirox (16 Years or Older)
Hide Arm/Group Description:
Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight.
Participants age 16 years or older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight.
Overall Number of Participants Analyzed 162 71
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
Core Baseline LIC 1-<7 mg Fe/g dw (n=20, 2)
75.0
(56.0 to 94.0)
100
(15.8 to 100)
Core Baseline LIC 7-<10 mg Fe/g dw (n=18, 8)
72.2
(51.5 to 92.9)
50.0
(15.7 to 84.3)
Core Baseline LIC ≥10 mg Fe/g dw (n=124, 61)
76.6
(69.2 to 84.1)
73.8
(62.7 to 84.8)
2.Primary Outcome
Title Absolute Change in Liver Iron Concentration (LIC)Measured by Liver MRI or Liver Biopsy From Core Study Baseline (BL) to End of Extension Study, by LIC Category
Hide Description

Liver MRI or Liver Biopsy was performed at the core study baseline (BL) and then 1 year and 2 years in the core study, baseline of the extension study and time of discontinuation from the extension visit (end of study). Liver iron content (LIC) is reported in milligram Iron per gram dry weight (mg Fe/g dw).

Absolute change in LIC from core study baseline to the end of the extension study is presented for participants with the following two core study baseline LIC levels: 1-<7 mg Fe/g dw and ≥7 mg Fe/g dw.

Time Frame From Baseline of Core Study to End of Extension Study, up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-Treat (ITT) population for whom LIC data was available at Core Study baseline and at the End of Extension Study. “n” is the number of participants analyzed in each category.
Arm/Group Title Deferasirox (Between 2 <16 Years) Deferasirox (16 Years or Older)
Hide Arm/Group Description:
Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight.
Participants age 16 years or older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight.
Overall Number of Participants Analyzed 119 41
Mean (Standard Deviation)
Unit of Measure: mg Fe/g dw
Core Baseline LIC 1-<7 mg Fe/g dw (n=12, 0) -1.32  (3.125) NA [1]   (NA)
Core Baseline LIC ≥7 mg Fe/g dw (n=107, 41) -9.03  (9.260) -8.39  (11.312)
[1]
No participants in this category for this group.
3.Secondary Outcome
Title Absolute Change in Serum Ferritin Level Measured From Core Study Baseline (BL) to End of Extension Study
Hide Description Serum Levels were assessed at core study baseline (BL), 1 year, 2 years in core study, baseline of extension study and time of discontinuation from the extension visit (end of study) in monthly intervals. Serum Ferritin is reported in micrograms per Liter (µg/L).
Time Frame From Baseline of Core Study to End of Extension Study, up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-Treat (ITT) population for whom Serum Ferritin data was available at Core Study baseline and at the End of Extension Study.
Arm/Group Title Deferasirox (Between 2 <16 Years) Deferasirox (16 Years or Older)
Hide Arm/Group Description:
Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight.
Participants age 16 years or older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight.
Overall Number of Participants Analyzed 120 43
Mean (Standard Deviation)
Unit of Measure: µg/L
-1432.51  (1969.622) -1791.91  (2712.334)
4.Secondary Outcome
Title Absolute Change in Serum Ferritin Level for All Participants Measured From Core Study Baseline (BL) to End of Extension Study, by Baseline Liver Iron Content (LIC)
Hide Description Serum Levels were assessed at core study baseline (BL) and then 1 year and 2 years in core study, baseline of extension study and time of discontinuation from the extension visit (end of study). Serum Ferritin is reported in micrograms per Liter. Absolute change in Serum Ferritin from core study baseline to the end of the extension study is presented for participants with the following two core study baseline LIC levels: 1-<7 mg Fe/g dw and ≥7 mg Fe/g dw.
Time Frame From Baseline of Core Study to End of Extension Study, up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the Intent-to-Treat (ITT) population for whom Serum Ferritin data was available at Core Study baseline and at the End of Extension Study. “n” is the number of participants analyzed in each category.
Arm/Group Title Deferasirox (All Participants)
Hide Arm/Group Description:
Participants received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient's body weight.
Overall Number of Participants Analyzed 163
Mean (Standard Deviation)
Unit of Measure: µg/L
Core Baseline LIC 1-<7 mg Fe/g dw (n=12) -369.83  (1349.57)
Core Baseline LIC ≥ 7 mg Fe/g dw (n=151) -1619.31  (2217.104)
Time Frame From baseline to end of study, up to 2 years
Adverse Event Reporting Description Adverse Events were calculated for the Safety Population consisting of all participants who received study drug in this Extension study. (162 participants between 2 < 16 years, 69 participants 16 years or older. Total 231 participants in Safety Population.)
 
Arm/Group Title Deferasirox (Between 2 <16 Years) Deferasirox (16 Years or Older)
Hide Arm/Group Description Participants age 2 years up to 16 years received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient’s body weight. Participants age 16 years and older received a daily oral dose of deferasirox. Dose selection was based on the dose last received in the core study. The individual daily doses of deferasirox and the exact amount of tablets (125, 250, or 500 mg) contributing to each dose were calculated by the investigator based on the patient’s body weight.
All-Cause Mortality
Deferasirox (Between 2 <16 Years) Deferasirox (16 Years or Older)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Deferasirox (Between 2 <16 Years) Deferasirox (16 Years or Older)
Affected / at Risk (%) Affected / at Risk (%)
Total   5/162 (3.09%)   12/69 (17.39%) 
Cardiac disorders     
Arrhythmia  1  0/162 (0.00%)  1/69 (1.45%) 
Cardiac failure  1  1/162 (0.62%)  0/69 (0.00%) 
Cardiac failure congestive  1  0/162 (0.00%)  1/69 (1.45%) 
Cardio-respiratory arrest  1  1/162 (0.62%)  0/69 (0.00%) 
Gastrointestinal disorders     
Abdominal pain upper  1  0/162 (0.00%)  3/69 (4.35%) 
Intestinal obstruction  1  0/162 (0.00%)  1/69 (1.45%) 
Melaena  1  0/162 (0.00%)  1/69 (1.45%) 
Peptic ulcer perforation  1  0/162 (0.00%)  1/69 (1.45%) 
Vomiting  1  1/162 (0.62%)  1/69 (1.45%) 
General disorders     
Pyrexia  1  0/162 (0.00%)  1/69 (1.45%) 
Hepatobiliary disorders     
Cholecystitis  1  0/162 (0.00%)  1/69 (1.45%) 
Infections and infestations     
Appendicitis  1  0/162 (0.00%)  1/69 (1.45%) 
Lower respiratory tract infection  1  1/162 (0.62%)  0/69 (0.00%) 
Otitis media  1  1/162 (0.62%)  0/69 (0.00%) 
Perinephric abscess  1  0/162 (0.00%)  1/69 (1.45%) 
Pneumonia streptococcal  1  1/162 (0.62%)  0/69 (0.00%) 
Sepsis  1  0/162 (0.00%)  1/69 (1.45%) 
Subdiaphragmatic abscess  1  1/162 (0.62%)  0/69 (0.00%) 
Wound infection  1  0/162 (0.00%)  1/69 (1.45%) 
Injury, poisoning and procedural complications     
Fall  1  0/162 (0.00%)  1/69 (1.45%) 
Femur fracture  1  0/162 (0.00%)  1/69 (1.45%) 
Hip fracture  1  0/162 (0.00%)  1/69 (1.45%) 
Perinephric collection  1  0/162 (0.00%)  1/69 (1.45%) 
Road traffic accident  1  0/162 (0.00%)  2/69 (2.90%) 
Upper limb fracture  1  0/162 (0.00%)  3/69 (4.35%) 
Investigations     
Blood creatinine increased  1  0/162 (0.00%)  1/69 (1.45%) 
Nervous system disorders     
Cerebral haemorrhage  1  0/162 (0.00%)  1/69 (1.45%) 
Coma  1  0/162 (0.00%)  1/69 (1.45%) 
Convulsion  1  1/162 (0.62%)  0/69 (0.00%) 
Headache  1  1/162 (0.62%)  1/69 (1.45%) 
Subarachnoid haemorrhage  1  0/162 (0.00%)  1/69 (1.45%) 
Respiratory, thoracic and mediastinal disorders     
Adenoidal hypertrophy  1  1/162 (0.62%)  0/69 (0.00%) 
Dyspnoea  1  0/162 (0.00%)  1/69 (1.45%) 
Vascular disorders     
Aneurysm  1  0/162 (0.00%)  1/69 (1.45%) 
Haemorrhage  1  0/162 (0.00%)  1/69 (1.45%) 
Hypotension  1  0/162 (0.00%)  1/69 (1.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Deferasirox (Between 2 <16 Years) Deferasirox (16 Years or Older)
Affected / at Risk (%) Affected / at Risk (%)
Total   54/162 (33.33%)   33/69 (47.83%) 
Gastrointestinal disorders     
Nausea  1  1/162 (0.62%)  5/69 (7.25%) 
Vomiting  1  17/162 (10.49%)  5/69 (7.25%) 
General disorders     
Pain  1  0/162 (0.00%)  5/69 (7.25%) 
Pyrexia  1  3/162 (1.85%)  6/69 (8.70%) 
Infections and infestations     
Gastroenteritis  1  1/162 (0.62%)  4/69 (5.80%) 
Influenza  1  26/162 (16.05%)  3/69 (4.35%) 
Upper respiratory tract infection  1  3/162 (1.85%)  8/69 (11.59%) 
Investigations     
Alanine aminotransferase increased  1  13/162 (8.02%)  4/69 (5.80%) 
Blood calcium decreased  1  0/162 (0.00%)  4/69 (5.80%) 
Blood creatinine increased  1  5/162 (3.09%)  9/69 (13.04%) 
Musculoskeletal and connective tissue disorders     
Osteoporosis  1  1/162 (0.62%)  4/69 (5.80%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
An internal review revealed major Good Clinical Practice violations at 2 sites in Saudi Arabia: 602 for core + extension, 601 for 2-yr extension. Therefore data was excluded (completely for 602 + partly for 601) from analyses.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00171301     History of Changes
Other Study ID Numbers: CICL670A2402E1
First Submitted: September 12, 2005
First Posted: September 15, 2005
Results First Submitted: January 12, 2011
Results First Posted: July 29, 2011
Last Update Posted: August 31, 2011