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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00171821




Registration number
NCT00171821
Ethics application status
Date submitted
13/09/2005
Date registered
15/09/2005
Date last updated
11/02/2020

Titles & IDs
Public title
A Study Assessing the Efficacy and Safety of Deferasirox in Patients With Transfusion-dependent Iron Overload
Scientific title
A One Year, Open-label, Single-arm, Multi-center Trial Evaluating the Efficacy and Safety of Oral ICL670 (20 mg/kg/Day) in Patients Diagnosed With Transfusion-dependent Iron Overload
Secondary ID [1] 0 0
2004-003953-16
Secondary ID [2] 0 0
CICL670A2409
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transfusion-dependent Iron Overload 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Diet and Nutrition 0 0 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: ICL670 (Deferasirox) -

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate if fixed starting doses of ICL670, based on transfusion history and subsequent dose titration can provide clinically acceptable chelation as measured by serum ferritin
Timepoint [1] 0 0
at baseline and at 52 weeks
Secondary outcome [1] 0 0
To evaluate the safety and tolerability profile of in patients treated for up to 52 weeks
Timepoint [1] 0 0
Monthly
Secondary outcome [2] 0 0
Evaluate efficacy, tolerabilty and safety in the subgroup of patients with baseline LIC < 7 mg Fe/g dw
Timepoint [2] 0 0
Monthly
Secondary outcome [3] 0 0
Evaluate the relationship between serum ferritin and potential surrogate markers
Timepoint [3] 0 0
Monthly

Eligibility
Key inclusion criteria
* Patients presenting with transfusion-dependent anemias (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of = 1000 ng/ml
* Patients of either gender and aged = 2 years
* Female patients who have reached menarche and who are sexually active must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation.

Additional Inclusion Criteria for Adult Patients:

* Written informed consent by the patient

Additional Inclusion Criteria for Pediatric Patients:

* The definition of the term "pediatric" will be in accordance with local legislation. Parents or legal guardians will be fully informed by the investigator as to the requirements of the study. The pediatric patients themselves will be informed according to their capabilities in a language and terms that they are able to understand. Written informed consent will be obtained from their parents or legal guardians on the patient's behalf in accordance with the national legislation. If capable, all patients should also personally sign their written informed assent.
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Non-transfusional hemosiderosis
* Patients with clinical evidence supporting the need for intensive chelation, based on the investigator's judgment
* Patients with mean levels of alanine aminotransferase (ALT) > 300 U/l
* Patients with uncontrolled systemic hypertension
* Patients with serum creatinine above the upper limit of normal (ULN)
* Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 (mg/mg) in second-voiding urine samples taken at both visits 1 and 2. A third sample is to be taken from patients in whom one ratio is > 0.5 (mg/mg) and one is = 0.5 (mg/mg) and patients in whom the urinary protein/creatinine ratio is > 0.5 (mg/mg) in two of the three determinations are also to be excluded.
* History of nephrotic syndrome
* Patients with 3rd atrioventricular (A-V) block, clinically relevant Q-T interval prolongation as well as patients requiring treatment with digoxin and similar compounds or drugs which may induce prolongation of the Q-T interval
* Patients with a previous history of clinically relevant ocular toxicity related to iron chelation
* Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment
* Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment
* Pregnant or breast feeding patients
* Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drugs within the past 7 days
* Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:

* history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;
* history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
* history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase;
* history or presence of impaired renal function as indicated by creatinine or blood urea nitrogen (BUN) values equal or above ULN;
* history of urinary obstruction or difficulty in voiding.
* History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
* History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the run-in period
* Patients with positive test to HIV
* Life expectancy of < 1 year

Exclusion Criteria for Pediatric Patients:

* Patient body weight which prevents the use of the smallest tablet strength (i.e. 125 mg) for proper dosing

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2010
Sample size
Target
Accrual to date
Final
1784
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [2] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [3] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [4] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [5] 0 0
Novartis Investigative Site - Perth
Recruitment hospital [6] 0 0
Novartis Investigative Site - South Brisbane
Recruitment hospital [7] 0 0
Novartis Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Camperdown
Recruitment postcode(s) [3] 0 0
- Clayton
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Perth
Recruitment postcode(s) [6] 0 0
- South Brisbane
Recruitment postcode(s) [7] 0 0
- Westmead
Recruitment outside Australia
Country [1] 0 0
Austria
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Graz
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Austria
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Linz
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Austria
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Wien
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Belgium
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Brussels
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Belgium
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Gent
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Belgium
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Godinne
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Belgium
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La Louviere
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Belgium
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Leuven
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China
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GuangZhou
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China
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Nanjing
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China
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Shanghai
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Denmark
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Arhus
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Denmark
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Copenhagen
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Denmark
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Herlev
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Denmark
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Hillerod
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Egypt
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Cairo
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France
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Angers
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France
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Avignon
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France
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Bobigny
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Creteil
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Lille Cedex
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Lyon
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Nice
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France
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Paris
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Pessac Cedex
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Rennes
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France
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Toulouse Cedex
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France
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Vandoeuvre Les Nancy
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Germany
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Augsburg
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Germany
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Braunschweig
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Dresden
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Frankfurt/Main
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Frankfurt
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Germany
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Frieburg
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Germany
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Gottingen
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Greifswald
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Hannover
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Mainz
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Muenchen
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Ulm
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Larissa
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Israel
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Afula
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Israel
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Jerusalem
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Palermo
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Pavia
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Pisa
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Reggio Calabria
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Roma
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Sassari
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Korea, Republic of
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Seoul
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Lebanon
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Hazmiyeh
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Malaysia
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Kota Bahru
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Malaysia
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Kuala Lumpur
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Netherlands
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Nijmegen
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South Africa
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South Africa
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Parktown
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Baracaldo
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Barcelona
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Madrid
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Sevilla
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Valencia
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Switzerland
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Geneve
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Zurich
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Chaingmai
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Adana
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Ankara
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Istanbul
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Izmir
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United Kingdom
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Leeds
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Leicester
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London
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Manchester
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United Kingdom
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Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study uses a single arm, multi-center, open-label trial design. The study will assess the efficacy and safety of 52 weeks of treatment with deferasirox (ICL670) in patients with evidence of transfusion induced iron overload.
Trial website
https://clinicaltrials.gov/study/NCT00171821
Trial related presentations / publications
Porter JB, El-Alfy M, Viprakasit V, Giraudier S, Chan LL, Lai Y, El-Ali A, Han J, Cappellini MD. Utility of labile plasma iron and transferrin saturation in addition to serum ferritin as iron overload markers in different underlying anemias before and after deferasirox treatment. Eur J Haematol. 2016 Jan;96(1):19-26. doi: 10.1111/ejh.12540. Epub 2015 Jun 23.
Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, El-Ali A, Habr D, Martin N, Porter JB. Hematologic responses in patients with aplastic anemia treated with deferasirox: a post hoc analysis from the EPIC study. Haematologica. 2013 Jul;98(7):1045-8. doi: 10.3324/haematol.2012.077669. Epub 2013 Apr 12.
Pennell DJ, Porter JB, Cappellini MD, Chan LL, El-Beshlawy A, Aydinok Y, Ibrahim H, Li CK, Viprakasit V, Elalfy MS, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Continued improvement in myocardial T2* over two years of deferasirox therapy in beta-thalassemia major patients with cardiac iron overload. Haematologica. 2011 Jan;96(1):48-54. doi: 10.3324/haematol.2010.031468. Epub 2010 Nov 11.
Lee JW, Yoon SS, Shen ZX, Ganser A, Hsu HC, Habr D, Domokos G, Roubert B, Porter JB; EPIC study investigators. Iron chelation therapy with deferasirox in patients with aplastic anemia: a subgroup analysis of 116 patients from the EPIC trial. Blood. 2010 Oct 7;116(14):2448-54. doi: 10.1182/blood-2010-01-261289. Epub 2010 Jun 21.
Pennell DJ, Porter JB, Cappellini MD, El-Beshlawy A, Chan LL, Aydinok Y, Elalfy MS, Sutcharitchan P, Li CK, Ibrahim H, Viprakasit V, Kattamis A, Smith G, Habr D, Domokos G, Roubert B, Taher A. Efficacy of deferasirox in reducing and preventing cardiac iron overload in beta-thalassemia. Blood. 2010 Mar 25;115(12):2364-71. doi: 10.1182/blood-2009-04-217455. Epub 2009 Dec 8.
Cappellini MD, Porter J, El-Beshlawy A, Li CK, Seymour JF, Elalfy M, Gattermann N, Giraudier S, Lee JW, Chan LL, Lin KH, Rose C, Taher A, Thein SL, Viprakasit V, Habr D, Domokos G, Roubert B, Kattamis A; EPIC Study Investigators. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias. Haematologica. 2010 Apr;95(4):557-66. doi: 10.3324/haematol.2009.014696. Epub 2009 Nov 30.
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00171821