Trial Outcomes & Findings for Extension Study of the Efficacy and Safety of Deferasirox Treatment in Beta-thalassemia Patients With Transfusional Hemosiderosis (Study Amended to 2-year Duration) (NCT NCT00171301)

Last Updated: 2011-08-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

233 participants

Primary outcome timeframe

From Core Study Baseline, to Extension End of Study, Up to 3 Years

Results posted on

2011-08-31

Participant Flow

This is an Extension to Core Study CICL670A2402 (NCT00171171). 233 participants completed the core study and entered this extension study.

2 participants from the 16 and older group did not receive deferasirox. Thus, the 16 and older group comprises of 69 treated participants.

Participant milestones

Participant milestones
Measure	Deferasirox (Between 2 <16 Years ) 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.	Deferasirox (16 Years or Older) 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 Study STARTED	162	71
Overall Study Received Deferasirox	162	69
Overall Study COMPLETED	154	62
Overall Study NOT COMPLETED	8	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Deferasirox (Between 2 <16 Years ) 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.	Deferasirox (16 Years or Older) 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 Study Death	1	2
Overall Study Adverse Event	1	2
Overall Study Lost to Follow-up	6	2
Overall Study Protocol Violation	0	2
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Deferasirox (Between 2 <16 Years ) n=162 Participants 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.	Deferasirox (16 Years or Older) n=71 Participants 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 n=233 Participants Total of all reporting groups
Age Continuous	9.5 years STANDARD_DEVIATION 3.59 • n=5 Participants	21.2 years STANDARD_DEVIATION 5.82 • n=7 Participants	13.0 years STANDARD_DEVIATION 6.93 • n=5 Participants
Sex/Gender, Customized Female	80 participants n=5 Participants	35 participants n=7 Participants	115 participants n=5 Participants
Sex/Gender, Customized Male	82 participants n=5 Participants	36 participants n=7 Participants	118 participants n=5 Participants

PRIMARY outcome

Timeframe: From Core Study Baseline, to Extension End of Study, Up to 3 Years

Population: 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.

Outcome measures

Outcome measures
Measure	Deferasirox (Between 2 <16 Years) n=162 Participants 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.	Deferasirox (16 Years or Older) n=71 Participants 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.
Percentage of Participants With Treatment Success From Core Baseline (BL) to Extension End of Study, by Baseline LIC Level and Age Core Baseline LIC 1-<7 mg Fe/g dw (n=20, 2)	75.0 percentage of participants Interval 56.0 to 94.0	100 percentage of participants Interval 15.8 to 100.0
Percentage of Participants With Treatment Success From Core Baseline (BL) to Extension End of Study, by Baseline LIC Level and Age Core Baseline LIC 7-<10 mg Fe/g dw (n=18, 8)	72.2 percentage of participants Interval 51.5 to 92.9	50.0 percentage of participants Interval 15.7 to 84.3
Percentage of Participants With Treatment Success From Core Baseline (BL) to Extension End of Study, by Baseline LIC Level and Age Core Baseline LIC ≥10 mg Fe/g dw (n=124, 61)	76.6 percentage of participants Interval 69.2 to 84.1	73.8 percentage of participants Interval 62.7 to 84.8

PRIMARY outcome

Timeframe: From Baseline of Core Study to End of Extension Study, up to 3 years

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Deferasirox (Between 2 <16 Years) n=119 Participants 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.	Deferasirox (16 Years or Older) n=41 Participants 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.
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 Core Baseline LIC 1-<7 mg Fe/g dw (n=12, 0)	-1.32 mg Fe/g dw Standard Deviation 3.125	NA mg Fe/g dw Standard Deviation NA No participants in this category for this group.
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 Core Baseline LIC ≥7 mg Fe/g dw (n=107, 41)	-9.03 mg Fe/g dw Standard Deviation 9.260	-8.39 mg Fe/g dw Standard Deviation 11.312

SECONDARY outcome

Timeframe: From Baseline of Core Study to End of Extension Study, up to 3 years

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Deferasirox (Between 2 <16 Years) n=120 Participants 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.	Deferasirox (16 Years or Older) n=43 Participants 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.
Absolute Change in Serum Ferritin Level Measured From Core Study Baseline (BL) to End of Extension Study	-1432.51 µg/L Standard Deviation 1969.622	-1791.91 µg/L Standard Deviation 2712.334

SECONDARY outcome

Timeframe: From Baseline of Core Study to End of Extension Study, up to 3 years

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Deferasirox (Between 2 <16 Years) n=163 Participants 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.	Deferasirox (16 Years or Older) 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.
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) Core Baseline LIC 1-<7 mg Fe/g dw (n=12)	-369.83 µg/L Standard Deviation 1349.57	—
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) Core Baseline LIC ≥ 7 mg Fe/g dw (n=151)	-1619.31 µg/L Standard Deviation 2217.104	—

Adverse Events

Deferasirox (Between 2 <16 Years)

Serious events: 5 serious events

Other events: 54 other events

Deaths: 0 deaths

Deferasirox (16 Years or Older)

Serious events: 12 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Deferasirox (Between 2 <16 Years) n=162 participants at risk 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.	Deferasirox (16 Years or Older) n=69 participants at risk 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.
Gastrointestinal disorders Nausea	0.62% 1/162 • From baseline to end of study, up to 2 years 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.)	7.2% 5/69 • From baseline to end of study, up to 2 years 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.)
Gastrointestinal disorders Vomiting	10.5% 17/162 • From baseline to end of study, up to 2 years 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.)	7.2% 5/69 • From baseline to end of study, up to 2 years 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.)
General disorders Pain	0.00% 0/162 • From baseline to end of study, up to 2 years 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.)	7.2% 5/69 • From baseline to end of study, up to 2 years 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.)
General disorders Pyrexia	1.9% 3/162 • From baseline to end of study, up to 2 years 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.)	8.7% 6/69 • From baseline to end of study, up to 2 years 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.)
Infections and infestations Gastroenteritis	0.62% 1/162 • From baseline to end of study, up to 2 years 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.)	5.8% 4/69 • From baseline to end of study, up to 2 years 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.)
Infections and infestations Influenza	16.0% 26/162 • From baseline to end of study, up to 2 years 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.)	4.3% 3/69 • From baseline to end of study, up to 2 years 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.)
Infections and infestations Upper respiratory tract infection	1.9% 3/162 • From baseline to end of study, up to 2 years 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.)	11.6% 8/69 • From baseline to end of study, up to 2 years 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.)
Investigations Alanine aminotransferase increased	8.0% 13/162 • From baseline to end of study, up to 2 years 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.)	5.8% 4/69 • From baseline to end of study, up to 2 years 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.)
Investigations Blood calcium decreased	0.00% 0/162 • From baseline to end of study, up to 2 years 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.)	5.8% 4/69 • From baseline to end of study, up to 2 years 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.)
Investigations Blood creatinine increased	3.1% 5/162 • From baseline to end of study, up to 2 years 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.)	13.0% 9/69 • From baseline to end of study, up to 2 years 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.)
Musculoskeletal and connective tissue disorders Osteoporosis	0.62% 1/162 • From baseline to end of study, up to 2 years 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.)	5.8% 4/69 • From baseline to end of study, up to 2 years 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.)

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER