Efficacy and Safety of Deferasirox in Patients With Chronic Anemia and Transfusional Hemosiderosis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00631163
• Collaborator: (none)
• Enrollment: 102
• Locations: 31
• Arm: 1
• Duration (Months): 52
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The overall purpose of this trial is to further evaluate the efficacy and safety of deferasirox, dosed initially according to the transfusional iron intake, in patients with transfusion dependant anemia related to disorders other than β-thalassemia and sickle cell disease.

During the study, the dose will be adjusted based on serum Ferritin.The overall purpose of the extension is to allow further treatment of patients who have already completed the core study, and to enable collection of long term efficacy and safety data. Patients will continue to receive Deferasirox at the dose they received at the end of the core study.

Condition or Disease	Intervention/Treatment	Phase
Chronic Anemia; Transfusional Hemosiderosis	Drug: Deferasirox (ICL670)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Center, Open-label, Non Comparative, Phase II Trial on Efficacy and Safety of ICL670 Given for 1 Year With Dose Adjustments Based on Serum Ferritin in Patients With Chronic Anemia and Transfusional Hemosiderosis Including an Additional 1 Year Extension.
• Study Start Date: Oct 1, 2007
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferasirox Participants received initial dose of 20 milligrams per kilogram (mg/kg) Deferasirox tablets was administered orally once daily (OD) based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.	Drug: Deferasirox (ICL670); The recommended initial daily dose of Deferasirox is 20 mg/kg body weight.; Other Names: ICL670

Outcome Measures

Primary Outcome Measures

1. Absolute Change From Baseline in Liver Iron Concentration (LIC) to Year 1 [From the Baseline, Year 1 (End of core study)]

   Liver iron concentration (LIC), a predictor of iron burden, was measured using relaxation rate magnetic resonance imaging (R2-MRI) technique. Relaxation rate was determined as R2 = 1/relaxation time (T2). The baseline value of LIC of participants was categorized as < 7, ≥ 7 to < 15, and ≥ 15 milligram of iron/tissue dry weight (mg Fe/g dw). A negative change from baseline favored study treatment in reducing LIC.

Secondary Outcome Measures

1. Absolute Change From Baseline in Liver Iron Concentration (LIC) to End of Year 2 [From the Baseline to End of Year 2 (End of extension study)]

   Liver Iron Concentration (LIC), a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC of participants was categorized as < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. A negative change from baseline favoured study treatment in reducing LIC.

2. Absolute Change From Baseline in Liver Iron Concentration (LIC) in Japanese Subgroup [From the Baseline, End of Year 1 (End of core study), End of Year 2 (End of extension study)]

   Liver Iron Concentration (LIC), a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC was < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. A negative change from baseline favoured study treatment in reducing LIC.

3. Absolute Change From Baseline in Serum Ferritin Levels to Year 2 [From the Baseline up to Year 2 (End of extension study)]

   Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content.

4. Absolute Serum Ferritin Levels Over 2 Years [From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)]

   Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content.

5. Total Body Iron Elimination Rate (TBIE), Iron Intake, Iron Excretion/Iron Intake and Chelation Efficiency After 2 Years [From the Baseline, Year 2 (End of extension study)]

   Total body iron excretion (TBIE)was used to investigate the chelation efficacy of Deferasirox therapy. TBIE rate was estimated based on the iron influx as determined by the amount of red cells transfused and the change in total body iron (TBI) stores.

6. Correlation of LIC and Serum Ferritin at Core and Extension Study [From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)]

   LIC, a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC was < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content. The correlation between absolute change in LIC and absolute change in serum ferritin was determined.

7. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESI), Discontinuation and Interruption [From the Baseline up to Year 2 (End of extension study)]

   Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. Death was defined as a fatal event leading to permanent cessation of all vital functions of the body.

8. Number of Participants With Clinically Significant Ophthalmological Abnormalities [At 2 years (End of extension study)]

   Clinically significant changes in left eye and right eye were assessed by the investigator based on methods like visual acuity, slit lamp examination, tonometry and fundus oculi.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria (Core):

• Patients with transfusional iron overload due to:

• low or intermediate (INT-1) risk Myelodysplastic Syndrome (MDS)determined via International Prognosis Scoring System (IPSS) criteria

• other congenital or acquired anemias excluding B-thalassemia and sickle cell disease

• Lifetime transfusion history of ≥20 unit (approximately 100 mL/kg) of packed red blood cells or showing evidence of iron overload (serum ferritin >1000 µg/L).

• Able to provide written informed consent

• Life expectancy ≥ 12 months If patient was previously treated with deferiprone, a washout period of one month should occur before the first dose of deferasirox

Inclusion criteria (Extension):

• Patients completing the planned 12-month core study (CICL670A2204).

• Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with national legislation.

Exclusion criteria (Core and Extension):

• Patients with β-thalassemia, sickle cell disease or myelodysplastic syndrome with an IPSS score being Intermediate-2 or High.

• Patients with serum creatinine > ULN

• Patients with ALT(SGPT) levels > 5 x ULN

• Significant proteinuria as indicated by a urinary protein/creatinine ratio >0.5 mg/mg in a non-first void urine sample on two assessments during the screening period.

• History of HIV positive test result , or of clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive and ALT above the normal range)

• Patients on investigational MDS therapies, including lenalidomide, thalidomide, azacitidine and arsenic trioxide, must have a ≥ 4 week washout period prior to the first dose of study drug.

• Patients with systemic uncontrolled hypertension

• Patients with unstable cardiac disease not controlled by standard medical therapy

• Systemic disease (cardiovascular, renal, hepatic, etc.) which would prevent study treatment

• Pregnancy (as documented in required screening laboratory test) or breast feeding.

• Patients treated with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days

• Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug

• Patients being considered by the investigator potentially unreliable and/or not cooperative with regard to the study protocol

• History of hypersensitivity to any of the study drug or excipients

• Sexually active pre-menopausal female patients without adequate contraception. Female patients must use effective contraception or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.

Other protocol defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Nagoya	Aichi	Japan	453-8511
2	Novartis Investigative Site	Nagoya	Aichi	Japan	466-8560
3	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	814-0180
4	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	060-8543
5	Novartis Investigative Site	Nishinomiya	Hyogo	Japan	663-8501
6	Novartis Investigative Site	Kahoku-gun	Ishikawa	Japan	920-0293
7	Novartis Investigative Site	Kanazawa	Ishikawa	Japan	920-8641
8	Novartis Investigative Site	OsakaSayama	Osaka	Japan	589-8511
9	Novartis Investigative Site	Suita-city	Osaka	Japan	565-0871
10	Novartis Investigative Site	Shimotsuka-gun	Tochigi	Japan	321-0293
11	Novartis Investigative Site	Simotsuke-city	Tochigi	Japan	329-0498
12	Novartis Investigative Site	Bunkyo-ku	Tokyo	Japan	113-8655
13	Novartis Investigative Site	Cyuo-ku	Tokyo	Japan	104-8560
14	Novartis Investigative Site	Minato-ku	Tokyo	Japan	108-8639
15	Novartis Investigative Site	Shinagawa-ku	Tokyo	Japan	141-8625
16	Novartis Investigative Site	Shinjuku-ku	Tokyo	Japan	160-0023
17	Novartis Investigative Site	Shinjuku-ku	Tokyo	Japan	162-8666
18	Novartis Investigative Site	Hiroshima		Japan	734-8551
19	Novartis Investigative Site	Kumamoto		Japan	860-0811
20	Novartis Investigative Site	Kyoto		Japan	606-8507
21	Novartis Investigative Site	Nagasaki		Japan	852-8501
22	Novartis Investigative Site	Toyama		Japan	930-8550
23	Novartis Investigative Site	Warszawa		Poland	02-097
24	Novartis Investigative Site	Warszawa		Poland	02-776
25	Novartis Investigative Site	Singapore		Singapore	169608
26	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007
27	Novartis Investigative Site	Valencia		Spain	46026
28	Novartis Investigative Site	Adana		Turkey	01330
29	Novartis Investigative Site	Ankara		Turkey	06100
30	Novartis Investigative Site	Istanbul		Turkey	34093
31	Novartis Investigative Site	Izmir		Turkey	35040

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
• Study Director: Novartis Pharmaceuticals, Novartis Pharmeceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CICL670A2204 Results at Novartis Clinical Trials Results Website

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00631163
• Other Study ID Numbers: CICL670A2204; 2006-003337-32; NCT01199003
• First Posted: Mar 7, 2008
• Last Update Posted: Jun 29, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Novartis Pharmaceuticals: Iron Overload,; Chelation,; MDS,; Chronic Anemia,; Deferasirox,; Transfusional hemosiderosis,
• Additional relevant MeSH terms: Anemia; Hemochromatosis; Hemosiderosis; Deferasirox

Study Results

Participant Flow

Recruitment Details	The study was conducted at 31 centers and five countries.
Pre-assignment Detail	A total of 144 Participants were screened, of which only 102 Participants enrolled in the study. Remaining 42 Participants were considered as screen failures.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received initial dose of 20 milligrams per kilogram (mg/kg) Deferasirox tablets was administered orally once daily (OD) based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Period Title: Number of Participants in Year 1
STARTED	102
COMPLETED	68
NOT COMPLETED	34
Period Title: Number of Participants in Year 1
STARTED	57
COMPLETED	52
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Overall Participants	102
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.8 (25.90)
Sex: Female, Male (Count of Participants)
Female	49 48%
Male	53 52%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	46 45.1%
Asian	56 54.9%
Race/Ethnicity, Customized (Count of Participants)
Japanese	53 52%
Other	43 42.2%
Hispanic or Latino	4 3.9%
Chinese	2 2%

Outcome Measures

1. Primary Outcome

Title	Absolute Change From Baseline in Liver Iron Concentration (LIC) to Year 1
Description	Liver iron concentration (LIC), a predictor of iron burden, was measured using relaxation rate magnetic resonance imaging (R2-MRI) technique. Relaxation rate was determined as R2 = 1/relaxation time (T2). The baseline value of LIC of participants was categorized as < 7, ≥ 7 to < 15, and ≥ 15 milligram of iron/tissue dry weight (mg Fe/g dw). A negative change from baseline favored study treatment in reducing LIC.
Time Frame	From the Baseline, Year 1 (End of core study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in per-protocol population in core study (PP1 Set), comprising of all enrolled participants who had LIC assessments at baseline and Year 1.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	50
Mean (Standard Deviation) [mg Fe/g dw]	-10.9 (11.86)

2. Secondary Outcome

Title	Absolute Change From Baseline in Liver Iron Concentration (LIC) to End of Year 2
Description	Liver Iron Concentration (LIC), a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC of participants was categorized as < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. A negative change from baseline favoured study treatment in reducing LIC.
Time Frame	From the Baseline to End of Year 2 (End of extension study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in per-protocol population in core study (PP2 Set), comprising of all enrolled participants who had LIC assessments at baseline and at end of the extension phase.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	41
Mean (Standard Deviation) [mg Fe/g dw]	-13.5 (14.10)

3. Secondary Outcome

Title	Absolute Change From Baseline in Liver Iron Concentration (LIC) in Japanese Subgroup
Description	Liver Iron Concentration (LIC), a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC was < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. A negative change from baseline favoured study treatment in reducing LIC.
Time Frame	From the Baseline, End of Year 1 (End of core study), End of Year 2 (End of extension study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in PP1 set in Japanese subgroup defined as all participants who were enrolled in Japan for core study (Year 1) and PP2 set in Japanese subgroup for extension study (Year 2). Here, 'n' signifies the participants reviewed for Liver Iron Concentration (LIC) in Japanese subgroup for each group, respectively.

Arm/Group Title	Deferasirox
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	57
Year 1	-13.9 (10.21)
Year 2	-18.4 (12.48)

4. Secondary Outcome

Title	Absolute Change From Baseline in Serum Ferritin Levels to Year 2
Description	Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content.
Time Frame	From the Baseline up to Year 2 (End of extension study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in PP2 Set population and Japanese subgroup. Here, "Number of subjects analyzed" signifies the participants assessed for serum ferritin during the study for each arm, respectively.

Arm/Group Title	All Randomized Participants	Japanese Participants
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	102	53
Mean (Standard Deviation) [nanogram(s)/millilitre]	-677.9 (4462.11)	-892.8 (5724.89)

5. Secondary Outcome

Title	Absolute Serum Ferritin Levels Over 2 Years
Description	Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content.
Time Frame	From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in PP1 set population for core study (Year 1) and PP2 set population for extension study (Year 2) and Japanese subgroup. Here, "Number of participants analysed" signifies the subjects assessed for serum ferritin during the study for each arm, respectively.

Arm/Group Title	All Randomized Participants	Japanese Participants
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	50	31
Year 1	2653.3 (2952.07)	2903.5 (3376.00)
Year 2	2092.4 (2287.11)	2114.8 (2391.31)

6. Secondary Outcome

Title	Total Body Iron Elimination Rate (TBIE), Iron Intake, Iron Excretion/Iron Intake and Chelation Efficiency After 2 Years
Description	Total body iron excretion (TBIE)was used to investigate the chelation efficacy of Deferasirox therapy. TBIE rate was estimated based on the iron influx as determined by the amount of red cells transfused and the change in total body iron (TBI) stores.
Time Frame	From the Baseline, Year 2 (End of extension study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in PP2 set population and Japanese/tim subgroup. Here, "Number of participants analyzed" included all participants who were evaluable for the specified categories.

Arm/Group Title	Deferasirox (Extension Study)	Japanese Participants
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	41	26
TBIE	0.46 (0.252)	0.54 (0.215)
Iron intake	0.27 (0.150)	0.27 (0.160)
Iron excretion/iron intake	2.00 (1.368)	2.44 (1.417)
Chelation efficiency	0.40 (0.221)	0.50 (0.177)

7. Secondary Outcome

Title	Correlation of LIC and Serum Ferritin at Core and Extension Study
Description	LIC, a predictor of iron burden, was measured using R2-MRI technique. Relaxation rate was determined as R2 = 1/T2. The baseline value of LIC was < 7, ≥ 7 to < 15, and ≥ 15 mg Fe/g dw. Serum ferritin was a marker for the monitoring of chelation therapy. Ferritin protein stores iron and provides overall iron levels, higher ferritin in blood showed more iron content. The correlation between absolute change in LIC and absolute change in serum ferritin was determined.
Time Frame	From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in PP1 set for core study (Year 1) and PP2 set for extension study (Year 2). Here, "Number of subjects analysed" signifies the subjects assessed for LIC and serum ferritin during the study for each arm, respectively.

Arm/Group Title	Deferasirox (Core Study)	Deferasirox (Extension Study)
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	50	40
Number [Correlation coefficient]	0.291	0.325

8. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESI), Discontinuation and Interruption
Description	Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. Death was defined as a fatal event leading to permanent cessation of all vital functions of the body.
Time Frame	From the Baseline up to Year 2 (End of extension study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the safety set (SAF) population, defined as subjects who received at least one dose of study drug, which was defined as at least one administration record with a valid date and an actual total daily dose administrated above zero, and Japanese sub-group.

Arm/Group Title	All Randomized Participants
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	102
Adverse Events	97 95.1%
Serious Adverse Events (SAE)	46 45.1%
Serious Adverse Events (SAE) with suspected relationship to study drug	10 9.8%
Death	6 5.9%
Adverse event leading to discontinuation of study drug	14 13.7%
Adverse event leading to dose adjustment/interruption	67 65.7%
Adverse Event of Special Interest (AESI)	62 60.8%
Adverse Event With Suspected Relationship to Study drug	65 63.7%

9. Secondary Outcome

Title	Number of Participants With Clinically Significant Ophthalmological Abnormalities
Description	Clinically significant changes in left eye and right eye were assessed by the investigator based on methods like visual acuity, slit lamp examination, tonometry and fundus oculi.
Time Frame	At 2 years (End of extension study)

Outcome Measure Data

Analysis Population Description

The analysis was performed in the SAF population, defined as subjects who received at least one dose of study drug, which was defined as at least one administration. These participants comprise 2 year completer groups

Arm/Group Title	All Randomized Participants
Arm/Group Description	Participants received initial dose of 20 mg/kg Deferasirox tablets was administered orally OD based on the Participants body weight. The dose of Deferasirox was adjusted to either 10 mg/kg or 30 mg/kg based on the volumes of blood transfusions being administered.
Measure Participants	50
Normal	24 23.5%
Abnormal, Clinically Insignificant	14 13.7%
Abnormal, Clinically Significant	9 8.8%
Not Available	3 2.9%
Total	50 49%

Adverse Events

Time Frame	From the Baseline up to Year 2 (End of extension study)
Adverse Event Reporting Description	The analysis was performed on safety set population defined as all participants who received study drug and had at least one post-baseline safety assessment.
Arm/Group Title	Myelodysplastic Syndrome		Aplastic Anemia		Other
Arm/Group Description	A group of disorders caused when something disrupts the production of blood cells.		Aplastic anemia is a condition that occurs when your body stops producing enough new blood cells. The condition leaves you fatigued and more prone to infections and uncontrolled bleeding.		Very rare diseases (e.g. Diamond Blackfan anemia, myelofibrosis, specific enzyme deficiency).
All Cause Mortality
	Myelodysplastic Syndrome		Aplastic Anemia		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/42 (4.8%)		3/29 (10.3%)		1/31 (3.2%)
Serious Adverse Events
	Myelodysplastic Syndrome		Aplastic Anemia		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/42 (52.4%)		14/29 (48.3%)		10/31 (32.3%)
Blood and lymphatic system disorders
ANAEMIA	1/42 (2.4%)		0/29 (0%)		1/31 (3.2%)
APLASTIC ANAEMIA	0/42 (0%)		3/29 (10.3%)		0/31 (0%)
DISSEMINATED INTRAVASCULAR COAGULATION	2/42 (4.8%)		1/29 (3.4%)		0/31 (0%)
FEBRILE NEUTROPENIA	0/42 (0%)		2/29 (6.9%)		1/31 (3.2%)
Cardiac disorders
ATRIAL FIBRILLATION	2/42 (4.8%)		0/29 (0%)		0/31 (0%)
ATRIAL FLUTTER	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
CARDIAC FAILURE	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
PERICARDITIS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
Endocrine disorders
DELAYED PUBERTY	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
Eye disorders
CATARACT	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
RETINAL HAEMORRHAGE	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
Gastrointestinal disorders
ASCITES	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
DIARRHOEA	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
ENTEROCOLITIS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
GASTROINTESTINAL HAEMORRHAGE	0/42 (0%)		2/29 (6.9%)		0/31 (0%)
GASTROINTESTINAL ULCER	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
PERIODONTAL DISEASE	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
PERIODONTITIS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
RADICULAR CYST	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
VOMITING	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
General disorders
CHEST DISCOMFORT	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
DISUSE SYNDROME	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
FATIGUE	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
GENERAL PHYSICAL HEALTH DETERIORATION	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
GENERALISED OEDEMA	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
MALAISE	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
MULTI-ORGAN FAILURE	2/42 (4.8%)		0/29 (0%)		0/31 (0%)
PYREXIA	6/42 (14.3%)		2/29 (6.9%)		1/31 (3.2%)
Hepatobiliary disorders
CHOLECYSTITIS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
HEPATIC FUNCTION ABNORMAL	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
Immune system disorders
HYPERSENSITIVITY	0/42 (0%)		2/29 (6.9%)		0/31 (0%)
Infections and infestations
BACTERIAL INFECTION	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
BRONCHITIS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
BRONCHOPNEUMONIA	1/42 (2.4%)		1/29 (3.4%)		0/31 (0%)
CELLULITIS	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
ENTEROCOLITIS INFECTIOUS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
FUNGAEMIA	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
FUNGAL OESOPHAGITIS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
GASTRITIS VIRAL	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
GASTROENTERITIS	0/42 (0%)		1/29 (3.4%)		1/31 (3.2%)
HERPES ZOSTER	1/42 (2.4%)		1/29 (3.4%)		0/31 (0%)
INFECTION	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
INFLUENZA	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
MENINGITIS	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
ORAL HERPES	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
PARONYCHIA	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
PERTUSSIS	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
PHARYNGITIS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
PNEUMONIA	4/42 (9.5%)		3/29 (10.3%)		0/31 (0%)
SEPSIS	2/42 (4.8%)		1/29 (3.4%)		0/31 (0%)
SEPTIC SHOCK	2/42 (4.8%)		0/29 (0%)		0/31 (0%)
URINARY TRACT INFECTION	3/42 (7.1%)		0/29 (0%)		0/31 (0%)
VIRAL INFECTION	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
ZYGOMYCOSIS	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
Injury, poisoning and procedural complications
CONTUSION	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
LUMBAR VERTEBRAL FRACTURE	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
TOOTH FRACTURE	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
TRAUMATIC HAEMORRHAGE	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
TRAUMATIC INTRACRANIAL HAEMORRHAGE	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
Investigations
BODY HEIGHT BELOW NORMAL	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
C-REACTIVE PROTEIN INCREASED	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
Metabolism and nutrition disorders
DEHYDRATION	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
HYPERCALCAEMIA	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
HYPERGLYCAEMIA	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
HYPOGLYCAEMIA	2/42 (4.8%)		0/29 (0%)		0/31 (0%)
HYPONATRAEMIA	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
Musculoskeletal and connective tissue disorders
BONE PAIN	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
BONE SWELLING	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
MUSCULOSKELETAL CHEST PAIN	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ABDOMINAL NEOPLASM	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
ACUTE MYELOID LEUKAEMIA	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
BLADDER NEOPLASM	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
MYELODYSPLASTIC SYNDROME	1/42 (2.4%)		1/29 (3.4%)		0/31 (0%)
MYELOFIBROSIS	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
RECTAL CANCER	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
Nervous system disorders
CEREBELLAR HAEMORRHAGE	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
CEREBRAL HAEMORRHAGE	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
CEREBRAL INFARCTION	0/42 (0%)		1/29 (3.4%)		0/31 (0%)
CEREBROVASCULAR ACCIDENT	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
DIZZINESS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
Psychiatric disorders
NEUROSIS	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
Renal and urinary disorders
FANCONI SYNDROME ACQUIRED	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
NEPHROLITHIASIS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
Respiratory, thoracic and mediastinal disorders
ADENOIDAL HYPERTROPHY	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
HYPOXIA	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
Skin and subcutaneous tissue disorders
HAEMORRHAGE SUBCUTANEOUS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
PANNICULITIS	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
RASH ERYTHEMATOUS	1/42 (2.4%)		0/29 (0%)		0/31 (0%)
SKIN ULCER	0/42 (0%)		0/29 (0%)		1/31 (3.2%)
URTICARIA	2/42 (4.8%)		0/29 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Myelodysplastic Syndrome		Aplastic Anemia		Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/42 (92.9%)		25/29 (86.2%)		25/31 (80.6%)
Blood and lymphatic system disorders
ANAEMIA	5/42 (11.9%)		1/29 (3.4%)		1/31 (3.2%)
APLASTIC ANAEMIA	0/42 (0%)		2/29 (6.9%)		0/31 (0%)
FEBRILE NEUTROPENIA	0/42 (0%)		2/29 (6.9%)		1/31 (3.2%)
THROMBOCYTOPENIA	3/42 (7.1%)		2/29 (6.9%)		0/31 (0%)
Cardiac disorders
ATRIAL FIBRILLATION	4/42 (9.5%)		2/29 (6.9%)		0/31 (0%)
CARDIAC FAILURE	4/42 (9.5%)		2/29 (6.9%)		1/31 (3.2%)
TACHYCARDIA	3/42 (7.1%)		2/29 (6.9%)		1/31 (3.2%)
Eye disorders
CATARACT	4/42 (9.5%)		2/29 (6.9%)		0/31 (0%)
CONJUNCTIVAL HAEMORRHAGE	3/42 (7.1%)		1/29 (3.4%)		0/31 (0%)
EYE PAIN	1/42 (2.4%)		2/29 (6.9%)		0/31 (0%)
RETINAL HAEMORRHAGE	2/42 (4.8%)		3/29 (10.3%)		3/31 (9.7%)
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	0/42 (0%)		3/29 (10.3%)		1/31 (3.2%)
ABDOMINAL DISTENSION	3/42 (7.1%)		1/29 (3.4%)		0/31 (0%)
ABDOMINAL PAIN	7/42 (16.7%)		4/29 (13.8%)		2/31 (6.5%)
ABDOMINAL PAIN UPPER	2/42 (4.8%)		3/29 (10.3%)		1/31 (3.2%)
APHTHOUS STOMATITIS	1/42 (2.4%)		2/29 (6.9%)		1/31 (3.2%)
CONSTIPATION	13/42 (31%)		5/29 (17.2%)		3/31 (9.7%)
DENTAL CARIES	3/42 (7.1%)		2/29 (6.9%)		0/31 (0%)
DIARRHOEA	10/42 (23.8%)		7/29 (24.1%)		5/31 (16.1%)
GASTRITIS	1/42 (2.4%)		2/29 (6.9%)		0/31 (0%)
HAEMORRHOIDS	3/42 (7.1%)		3/29 (10.3%)		0/31 (0%)
NAUSEA	9/42 (21.4%)		6/29 (20.7%)		2/31 (6.5%)
STOMATITIS	8/42 (19%)		7/29 (24.1%)		0/31 (0%)
VOMITING	3/42 (7.1%)		4/29 (13.8%)		0/31 (0%)
General disorders
ASTHENIA	2/42 (4.8%)		2/29 (6.9%)		1/31 (3.2%)
CHEST PAIN	1/42 (2.4%)		3/29 (10.3%)		0/31 (0%)
FACE OEDEMA	2/42 (4.8%)		2/29 (6.9%)		0/31 (0%)
FATIGUE	2/42 (4.8%)		1/29 (3.4%)		3/31 (9.7%)
MALAISE	2/42 (4.8%)		4/29 (13.8%)		2/31 (6.5%)
OEDEMA PERIPHERAL	14/42 (33.3%)		7/29 (24.1%)		1/31 (3.2%)
PYREXIA	11/42 (26.2%)		9/29 (31%)		6/31 (19.4%)
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL	2/42 (4.8%)		2/29 (6.9%)		0/31 (0%)
Infections and infestations
BRONCHITIS	2/42 (4.8%)		0/29 (0%)		4/31 (12.9%)
CYSTITIS	5/42 (11.9%)		3/29 (10.3%)		0/31 (0%)
EAR INFECTION	0/42 (0%)		0/29 (0%)		2/31 (6.5%)
FURUNCLE	0/42 (0%)		2/29 (6.9%)		0/31 (0%)
HERPES SIMPLEX	3/42 (7.1%)		0/29 (0%)		0/31 (0%)
HERPES ZOSTER	4/42 (9.5%)		0/29 (0%)		0/31 (0%)
INFLUENZA	1/42 (2.4%)		3/29 (10.3%)		2/31 (6.5%)
NASOPHARYNGITIS	14/42 (33.3%)		10/29 (34.5%)		6/31 (19.4%)
ORAL CANDIDIASIS	3/42 (7.1%)		0/29 (0%)		0/31 (0%)
OTITIS MEDIA	0/42 (0%)		2/29 (6.9%)		1/31 (3.2%)
OTITIS MEDIA CHRONIC	0/42 (0%)		2/29 (6.9%)		0/31 (0%)
PHARYNGITIS	3/42 (7.1%)		1/29 (3.4%)		2/31 (6.5%)
TONSILLITIS	2/42 (4.8%)		0/29 (0%)		3/31 (9.7%)
UPPER RESPIRATORY TRACT INFECTION	1/42 (2.4%)		2/29 (6.9%)		9/31 (29%)
URINARY TRACT INFECTION	3/42 (7.1%)		0/29 (0%)		3/31 (9.7%)
Injury, poisoning and procedural complications
ALLERGIC TRANSFUSION REACTION	3/42 (7.1%)		1/29 (3.4%)		1/31 (3.2%)
CONTUSION	6/42 (14.3%)		3/29 (10.3%)		0/31 (0%)
FALL	2/42 (4.8%)		3/29 (10.3%)		0/31 (0%)
SPINAL COMPRESSION FRACTURE	1/42 (2.4%)		2/29 (6.9%)		0/31 (0%)
TOOTH INJURY	0/42 (0%)		2/29 (6.9%)		0/31 (0%)
TRANSFUSION REACTION	4/42 (9.5%)		2/29 (6.9%)		1/31 (3.2%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	3/42 (7.1%)		1/29 (3.4%)		3/31 (9.7%)
ASPARTATE AMINOTRANSFERASE INCREASED	1/42 (2.4%)		2/29 (6.9%)		1/31 (3.2%)
BLOOD ALKALINE PHOSPHATASE INCREASED	1/42 (2.4%)		3/29 (10.3%)		2/31 (6.5%)
BLOOD CREATININE INCREASED	16/42 (38.1%)		8/29 (27.6%)		2/31 (6.5%)
C-REACTIVE PROTEIN INCREASED	4/42 (9.5%)		5/29 (17.2%)		0/31 (0%)
PROTEIN URINE PRESENT	3/42 (7.1%)		1/29 (3.4%)		5/31 (16.1%)
WEIGHT DECREASED	2/42 (4.8%)		2/29 (6.9%)		2/31 (6.5%)
Metabolism and nutrition disorders
DECREASED APPETITE	7/42 (16.7%)		4/29 (13.8%)		1/31 (3.2%)
DEHYDRATION	5/42 (11.9%)		3/29 (10.3%)		0/31 (0%)
DIABETES MELLITUS	4/42 (9.5%)		2/29 (6.9%)		1/31 (3.2%)
HYPOGLYCAEMIA	4/42 (9.5%)		4/29 (13.8%)		1/31 (3.2%)
HYPOKALAEMIA	3/42 (7.1%)		0/29 (0%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	3/42 (7.1%)		1/29 (3.4%)		0/31 (0%)
BACK PAIN	7/42 (16.7%)		2/29 (6.9%)		1/31 (3.2%)
MUSCLE SPASMS	3/42 (7.1%)		3/29 (10.3%)		1/31 (3.2%)
MUSCULOSKELETAL PAIN	3/42 (7.1%)		1/29 (3.4%)		3/31 (9.7%)
MYALGIA	2/42 (4.8%)		1/29 (3.4%)		2/31 (6.5%)
PAIN IN EXTREMITY	5/42 (11.9%)		2/29 (6.9%)		3/31 (9.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MYELODYSPLASTIC SYNDROME	4/42 (9.5%)		1/29 (3.4%)		0/31 (0%)
Nervous system disorders
DYSGEUSIA	1/42 (2.4%)		2/29 (6.9%)		0/31 (0%)
HEADACHE	8/42 (19%)		4/29 (13.8%)		3/31 (9.7%)
SOMNOLENCE	1/42 (2.4%)		2/29 (6.9%)		1/31 (3.2%)
Psychiatric disorders
DELIRIUM	3/42 (7.1%)		0/29 (0%)		0/31 (0%)
INSOMNIA	6/42 (14.3%)		1/29 (3.4%)		1/31 (3.2%)
Renal and urinary disorders
PROTEINURIA	4/42 (9.5%)		1/29 (3.4%)		1/31 (3.2%)
RENAL FAILURE	4/42 (9.5%)		3/29 (10.3%)		2/31 (6.5%)
RENAL IMPAIRMENT	4/42 (9.5%)		6/29 (20.7%)		2/31 (6.5%)
Respiratory, thoracic and mediastinal disorders
COUGH	2/42 (4.8%)		2/29 (6.9%)		5/31 (16.1%)
DYSPNOEA	3/42 (7.1%)		1/29 (3.4%)		1/31 (3.2%)
EPISTAXIS	1/42 (2.4%)		2/29 (6.9%)		2/31 (6.5%)
NASAL CONGESTION	0/42 (0%)		0/29 (0%)		2/31 (6.5%)
OROPHARYNGEAL PAIN	1/42 (2.4%)		3/29 (10.3%)		1/31 (3.2%)
PRODUCTIVE COUGH	0/42 (0%)		2/29 (6.9%)		0/31 (0%)
RHINITIS ALLERGIC	0/42 (0%)		1/29 (3.4%)		2/31 (6.5%)
Skin and subcutaneous tissue disorders
DERMATITIS ALLERGIC	0/42 (0%)		0/29 (0%)		2/31 (6.5%)
DRY SKIN	1/42 (2.4%)		3/29 (10.3%)		4/31 (12.9%)
MADAROSIS	0/42 (0%)		0/29 (0%)		2/31 (6.5%)
PETECHIAE	3/42 (7.1%)		0/29 (0%)		1/31 (3.2%)
PRURITUS	2/42 (4.8%)		4/29 (13.8%)		1/31 (3.2%)
RASH	11/42 (26.2%)		3/29 (10.3%)		1/31 (3.2%)
SKIN ULCER	2/42 (4.8%)		0/29 (0%)		2/31 (6.5%)
Vascular disorders
HYPOTENSION	2/42 (4.8%)		2/29 (6.9%)		0/31 (0%)

Limitations/Caveats

[Not Specified]

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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.