Expanded Access of Deferasirox to Patients With Congenital Disorders of Red Blood Cells and Chronic Iron Overload

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ClinicalTrials.gov Identifier: NCT00235391

Recruitment Status : Completed

First Posted : October 10, 2005

Results First Posted : May 2, 2011

Last Update Posted : June 7, 2011

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by:

Novartis

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Thalassemia Sickle Cell Disease Diamond Blackfan Anemia Myelofibrosis
Intervention	Drug: Deferasirox
Enrollment	1683

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	2 to < 6 Years	6 to < 12 Years	12 to < 16 Years	16 to < 50 Years	50 to < 65 Years	≥ 65 Years
Arm/Group Description	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...
Arm/Group Description	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.
Period Title: Overall Study
Started	97	200	172	1164	43	7
Deferasirox Treatment	97	200	172	1164	43	7
Completed	85	182	148	944	31	3
Not Completed	12	18	24	220	12	4
Reason Not Completed
Adverse Event	4	5	10	72	5	2
Abnormal laboratory value(s)	3	5	4	27	1	2
Unsatisfactory therapeutic effect	0	2	2	17	0	0
Condition no longer requires treatment	3	0	0	11	1	0
Protocol deviation	0	0	1	11	0	0
Withdrawal by Subject	2	3	3	61	5	0
Lost to Follow-up	0	3	3	16	0	0
Administrative problems	0	0	0	1	0	0
Death	0	0	1	4	0	0

Baseline Characteristics

Arm/Group Title		2 to < 6 Years	6 to < 12 Years	12 to < 16 Years	16 to < 50 Years	50 to < 65 Years	≥ 65 Years	Total
Arm/Group Description		Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Total of all reporting groups
Arm/Group Description		Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Total of all reporting groups
Overall Number of Baseline Participants		97	200	172	1164	43	7	1683
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	97 participants	200 participants	172 participants	1164 participants	43 participants	7 participants	1683 participants
		3.48 (1.13)	8.52 (1.64)	13.48 (1.20)	28.91 (8.06)	54.58 (3.92)	70.14 (3.98)	24.27 (12.63)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	97 participants	200 participants	172 participants	1164 participants	43 participants	7 participants	1683 participants
	Female	44 45.4%	101 50.5%	81 47.1%	633 54.4%	32 74.4%	5 71.4%	896 53.2%
	Male	53 54.6%	99 49.5%	91 52.9%	531 45.6%	11 25.6%	2 28.6%	787 46.8%
Baseline Disease Characteristics ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	97 participants	200 participants	172 participants	1164 participants	43 participants	7 participants	1683 participants
Beta-Thalassemia Major		74	118	114	905	10	0	1221
Beta-Thalassemia Intermedia		1	22	16	94	20	3	156
Sickle Cell Disease		8	41	31	93	2	1	176
Diamond-Blackfan Anemia		4	7	8	24	0	0	43
Other Diseases		10	12	3	48	11	3	87
		[1] Measure Description: The number of participants with each disease category.
Prior Chelation Drug Therapy ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	97 participants	200 participants	172 participants	1164 participants	43 participants	7 participants	1683 participants
Deferoxamine		80	167	137	745	31	5	1165
Deferiprone		1	8	11	146	6	1	173
Deferoxamine and Deferiprone		2	16	21	269	6	0	314
Other Chelation Drug		6	6	3	4	0	0	19
Prior Chelatation Drug Information Missing		8	3	0	0	0	1	12
		[1] Measure Description: The number of participants for each chelation drug category.
Reason for inadequate prior chelation therapy ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	97 participants	200 participants	172 participants	1164 participants	43 participants	7 participants	1683 participants
Therapy non-compliance		57	125	106	659	25	2	974
Therapy contraindication		1	7	6	29	1	1	45
Therapy unacceptable toxicity		11	29	22	131	6	1	200
Therapy poor response		20	34	38	267	8	0	367
Therapy unacceptable discomfort		2	2	0	78	3	2	87
Reason for inadequate therapy information missing		6	3	0	0	0	1	10
		[1] Measure Description: The number of participants for each reason for inadequate prior chelation therapy category.

Outcome Measures

1.Primary Outcome


Title	Safety Profile of Deferasirox Based Upon Drug Administration and Reporting of Serious Adverse Events
Description	Safety as assessed by the number of participants with death, serious a...
Description	Safety as assessed by the number of participants with death, serious adverse events (SAE), and/or Adverse Events (AEs) leading to study drug interruption or discontinuation. Note: only treatment emergent AEs are summarized.
Time Frame	Baseline to end of study (Median exposure time to drug was approximately 30 weeks; Maximum exposure was 104 weeks)

Outcome Measure Data

Analysis Population Description

The safety population, comprising all participants who received at least one dose of deferasirox during the study, was used in the analyses.


Arm/Group Title	2 to < 6 Years	6 to < 12 Years	12 to < 16 Years	16 to < 50 Years	50 to < 65 Years	≥ 65 Years
Arm/Group Description:	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...
Arm/Group Description:	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.
Overall Number of Participants Analyzed	97	200	172	1164	43	7
Measure Type: Number Unit of Measure: Participants
Number of deaths	0	0	1	4	0	0
Non-fatal SAEs	10	22	27	129	4	2
AEs leading to discontinuation	4	5	10	75	5	2
AEs leading dose adjustment/temporary interruption	15	31	28	209	11	2

2.Secondary Outcome


Title	The Change in Serum Ferritin Values From Baseline Through Completion of the Study
Description	The number of participants with Improvement, No Change or Worsening in...
Description	The number of participants with Improvement, No Change or Worsening in Serum ferritin category levels at the end of the study compared to baseline. Serum ferritin levels in µg/L were divided into to 6 categories: (<1000), (1000-<2500), (2500-<4000), (4000-<5500), (5500-<7000) and (>=7000). Improvement was defined as a shift to a lower category at the end of study compared to the category at baseline. Worsening was defined as a shift to a higher category at the end of the study compared to the category at baseline. No change was no change in category at end of study from baseline.
Time Frame	Baseline to end of study (Median exposure time to drug was approximately 30 weeks; Maximum exposure was 104 weeks)

Outcome Measure Data

Analysis Population Description

Safety population defined as all participants who received at least one dose of study drug. This analysis did not include participants with unknown status at baseline and/or at the end of the study.


Arm/Group Title	2 to < 6 Years	6 to < 12 Years	12 to < 16 Years	16 to < 50 Years	50 to < 65 Years	≥ 65 Years
Arm/Group Description:	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...	Deferasirox was administered orally...
Arm/Group Description:	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.
Overall Number of Participants Analyzed	97	200	172	1164	43	7
Measure Type: Number Unit of Measure: Participants
Improvement	17	27	26	206	4	2
No Change	63	106	87	570	31	3
Worsening	16	63	55	341	7	1

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	All Participants
Arm/Group Description	Deferasirox was administered orally...
Arm/Group Description	Deferasirox was administered orally once a day, 30 minutes prior to breakfast. Dosage was based on participant's body weight. Tablets were dispersed in water, orange or apple juice.
All-Cause Mortality
	All Participants
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events Serious Adverse Events
	All Participants
	Affected / at Risk (%)
Total	194/1683 (11.53%)
Blood and lymphatic system disorders
Acute chest syndrome ^† 1	2/1683 (0.12%)
Anaemia ^† 1	2/1683 (0.12%)
Anaemia haemolytic autoimmune ^† 1	2/1683 (0.12%)
Coombs positive haemolytic anaemia ^† 1	1/1683 (0.06%)
Haemolytic anaemia ^† 1	1/1683 (0.06%)
Hypersplenism ^† 1	3/1683 (0.18%)
Intravascular haemolysis ^† 1	1/1683 (0.06%)
Leukopenia ^† 1	1/1683 (0.06%)
Neutropenia ^† 1	2/1683 (0.12%)
Pancytopenia ^† 1	1/1683 (0.06%)
Reticulocytopenia ^† 1	1/1683 (0.06%)
Splenomegaly ^† 1	4/1683 (0.24%)
Cardiac disorders
Arrhythmia ^† 1	1/1683 (0.06%)
Atrial fibrillation ^† 1	2/1683 (0.12%)
Cardiac failure ^† 1	6/1683 (0.36%)
Cardiac failure acute ^† 1	1/1683 (0.06%)
Cardiac failure congestive ^† 1	2/1683 (0.12%)
Congestive cardiomyopathy ^† 1	1/1683 (0.06%)
Myopericarditis ^† 1	1/1683 (0.06%)
Pericardial effusion ^† 1	1/1683 (0.06%)
Tachycardia ^† 1	1/1683 (0.06%)
Ventricular dysfunction ^† 1	1/1683 (0.06%)
Congenital, familial and genetic disorders
Hip dysplasia ^† 1	1/1683 (0.06%)
Sickle cell anaemia ^† 1	2/1683 (0.12%)
Sickle cell anaemia with crisis ^† 1	27/1683 (1.60%)
Thalassaemia ^† 1	1/1683 (0.06%)
Thalassaemia beta ^† 1	2/1683 (0.12%)
Ear and labyrinth disorders
Deafness unilateral ^† 1	1/1683 (0.06%)
Middle ear effusion ^† 1	1/1683 (0.06%)
Eye disorders
Retinopathy ^† 1	1/1683 (0.06%)
Gastrointestinal disorders
Abdominal discomfort ^† 1	1/1683 (0.06%)
Abdominal pain ^† 1	3/1683 (0.18%)
Abdominal pain upper ^† 1	2/1683 (0.12%)
Colitis ^† 1	1/1683 (0.06%)
Constipation ^† 1	1/1683 (0.06%)
Crohn's disease ^† 1	1/1683 (0.06%)
Diarrhoea ^† 1	1/1683 (0.06%)
Gastritis ^† 1	4/1683 (0.24%)
Gastrointestinal haemorrhage ^† 1	1/1683 (0.06%)
Haemorrhoids ^† 1	1/1683 (0.06%)
Pancreatitis ^† 1	1/1683 (0.06%)
Peritonitis ^† 1	1/1683 (0.06%)
Proctitis ^† 1	1/1683 (0.06%)
Vomiting ^† 1	1/1683 (0.06%)
General disorders
Catheter thrombosis ^† 1	1/1683 (0.06%)
Death ^† 1	1/1683 (0.06%)
Local swelling ^† 1	1/1683 (0.06%)
Malaise ^† 1	3/1683 (0.18%)
Non-cardiac chest pain ^† 1	5/1683 (0.30%)
Pain ^† 1	3/1683 (0.18%)
Pyrexia ^† 1	9/1683 (0.53%)
Hepatobiliary disorders
Biliary colic ^† 1	1/1683 (0.06%)
Cholelithiasis ^† 1	6/1683 (0.36%)
Hepatitis ^† 1	2/1683 (0.12%)
Hyperbilirubinaemia ^† 1	1/1683 (0.06%)
Liver disorder ^† 1	1/1683 (0.06%)
Immune system disorders
Hypersensitivity ^† 1	1/1683 (0.06%)
Infections and infestations
Abdominal infection ^† 1	1/1683 (0.06%)
Acute tonsillitis ^† 1	2/1683 (0.12%)
Appendicitis ^† 1	1/1683 (0.06%)
Bacterial infection ^† 1	1/1683 (0.06%)
Bronchitis ^† 1	2/1683 (0.12%)
Bronchopneumonia ^† 1	1/1683 (0.06%)
Catheter related infection ^† 1	1/1683 (0.06%)
Catheter site infection ^† 1	1/1683 (0.06%)
Cellulitis ^† 1	2/1683 (0.12%)
Diarrhoea infectious ^† 1	1/1683 (0.06%)
Ear infection ^† 1	1/1683 (0.06%)
Epstein-Barr virus infection ^† 1	3/1683 (0.18%)
Escherichia bacteraemia ^† 1	1/1683 (0.06%)
Gastroenteritis ^† 1	3/1683 (0.18%)
Gastrointestinal infection ^† 1	1/1683 (0.06%)
Hepatitis C ^† 1	1/1683 (0.06%)
Influenza ^† 1	1/1683 (0.06%)
Liver abscess ^† 1	1/1683 (0.06%)
Necrotising fasciitis ^† 1	1/1683 (0.06%)
Osteomyelitis ^† 1	2/1683 (0.12%)
Otitis media acute ^† 1	1/1683 (0.06%)
Parvovirus infection ^† 1	1/1683 (0.06%)
Perianal abscess ^† 1	1/1683 (0.06%)
Pharyngitis ^† 1	1/1683 (0.06%)
Pharyngitis streptococcal ^† 1	1/1683 (0.06%)
Pneumonia ^† 1	4/1683 (0.24%)
Pyelonephritis ^† 1	1/1683 (0.06%)
Respiratory tract infection ^† 1	2/1683 (0.12%)
Rhinitis ^† 1	1/1683 (0.06%)
Sepsis ^† 1	1/1683 (0.06%)
Tonsillitis ^† 1	1/1683 (0.06%)
Upper respiratory tract infection ^† 1	1/1683 (0.06%)
Viral infection ^† 1	5/1683 (0.30%)
Injury, poisoning and procedural complications
Clavicle fracture ^† 1	1/1683 (0.06%)
Comminuted fracture ^† 1	1/1683 (0.06%)
Femur fracture ^† 1	2/1683 (0.12%)
Forearm fracture ^† 1	1/1683 (0.06%)
Haemolytic transfusion reaction ^† 1	1/1683 (0.06%)
Post-traumatic pain ^† 1	1/1683 (0.06%)
Road traffic accident ^† 1	2/1683 (0.12%)
Spinal fracture ^† 1	1/1683 (0.06%)
Suture rupture ^† 1	1/1683 (0.06%)
Thermal burn ^† 1	1/1683 (0.06%)
Tibia fracture ^† 1	1/1683 (0.06%)
Upper limb fracture ^† 1	1/1683 (0.06%)
Investigations
Alanine aminotransferase increased ^† 1	2/1683 (0.12%)
Blood calcium increased ^† 1	1/1683 (0.06%)
Blood creatinine increased ^† 1	1/1683 (0.06%)
Cardiovascular evaluation ^† 1	1/1683 (0.06%)
Protein urine present ^† 1	1/1683 (0.06%)
Serum ferritin increased ^† 1	1/1683 (0.06%)
Transaminases increased ^† 1	1/1683 (0.06%)
Metabolism and nutrition disorders
Hyperglycaemia ^† 1	1/1683 (0.06%)
Hypocalcaemia ^† 1	1/1683 (0.06%)
Hypoglycaemic seizure ^† 1	1/1683 (0.06%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/1683 (0.06%)
Back pain ^† 1	1/1683 (0.06%)
Fistula ^† 1	1/1683 (0.06%)
Osteonecrosis ^† 1	1/1683 (0.06%)
Pain in extremity ^† 1	1/1683 (0.06%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thymus ^† 1	1/1683 (0.06%)
Hepatic neoplasm malignant recurrent ^† 1	1/1683 (0.06%)
Non-small cell lung cancer ^† 1	1/1683 (0.06%)
Nervous system disorders
Convulsion ^† 1	1/1683 (0.06%)
Headache ^† 1	2/1683 (0.12%)
Migraine ^† 1	1/1683 (0.06%)
Paraesthesia ^† 1	1/1683 (0.06%)
Spinal cord compression ^† 1	1/1683 (0.06%)
Pregnancy, puerperium and perinatal conditions
Pregnancy ^† 1	5/1683 (0.30%)
Psychiatric disorders
Anxiety ^† 1	1/1683 (0.06%)
Depression ^† 1	1/1683 (0.06%)
Suicide attempt ^† 1	1/1683 (0.06%)
Renal and urinary disorders
Calculus ureteric ^† 1	1/1683 (0.06%)
Nephrotic syndrome ^† 1	1/1683 (0.06%)
Renal colic ^† 1	2/1683 (0.12%)
Renal failure ^† 1	2/1683 (0.12%)
Urethral stenosis ^† 1	1/1683 (0.06%)
Urinary retention ^† 1	1/1683 (0.06%)
Reproductive system and breast disorders
Haemorrhagic ovarian cyst ^† 1	1/1683 (0.06%)
Uterine disorder ^† 1	1/1683 (0.06%)
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy ^† 1	1/1683 (0.06%)
Asthma ^† 1	1/1683 (0.06%)
Dyspnoea ^† 1	1/1683 (0.06%)
Epistaxis ^† 1	1/1683 (0.06%)
Hypoxia ^† 1	1/1683 (0.06%)
Pleural effusion ^† 1	1/1683 (0.06%)
Pneumonitis ^† 1	1/1683 (0.06%)
Pulmonary embolism ^† 1	2/1683 (0.12%)
Skin and subcutaneous tissue disorders
Erythema multiforme ^† 1	1/1683 (0.06%)
Pigmentation disorder ^† 1	1/1683 (0.06%)
Rash ^† 1	5/1683 (0.30%)
Rash maculo-papular ^† 1	2/1683 (0.12%)
Swelling face ^† 1	1/1683 (0.06%)
Urticaria ^† 1	1/1683 (0.06%)
Surgical and medical procedures
Uterine dilation and curettage ^† 1	1/1683 (0.06%)
Vascular disorders
Deep vein thrombosis ^† 1	1/1683 (0.06%)
Hypotension ^† 1	1/1683 (0.06%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	All Participants
	Affected / at Risk (%)
Total	85/1683 (5.05%)
Skin and subcutaneous tissue disorders
Rash ^† 1	85/1683 (5.05%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA

Limitations and Caveats

[Not Specified]

More Information

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:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00235391
Other Study ID Numbers:	CICL670A2203
First Submitted:	October 6, 2005
First Posted:	October 10, 2005
Results First Submitted:	December 17, 2010
Results First Posted:	May 2, 2011
Last Update Posted:	June 7, 2011

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