Transfusion-dependent Iron Overload Clinical Trial
Official 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
| Verified date | June 2013 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 1784 |
| Est. completion date | July 2010 |
| Est. primary completion date | May 2009 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years and older |
| Eligibility |
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. 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. |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Novartis Investigative Site | Adelaide | |
| Australia | Novartis Investigative Site | Camperdown | |
| Australia | Novartis Investigative Site | Clayton | |
| Australia | Novartis Investigative Site | Melbourne | |
| Australia | Novartis Investigative Site | Perth | |
| Australia | Novartis Investigative Site | South Brisbane | |
| Australia | Novartis Investigative Site | Westmead | |
| Austria | Novartis Investigative Site | Graz | |
| Austria | Novartis Investigative Site | Linz | |
| Austria | Novartis Investigative Site | Wien | |
| Belgium | Novartis Investigative Site | Brussels | |
| Belgium | Novartis Investigative Site | Gent | |
| Belgium | Novartis Investigative Site | Godinne | |
| Belgium | Novartis Investigative Site | La Louviere | |
| Belgium | Novartis Investigative Site | Leuven | |
| China | Novartis Investigative Site | GuangZhou | |
| China | Novartis Investigative Site | Nanjing | |
| China | Novartis Investigative Site | Shanghai | |
| Denmark | Novartis Investigative Site | Arhus | |
| Denmark | Novartis Investigative Site | Copenhagen | |
| Denmark | Novartis Investigative Site | Herlev | |
| Denmark | Novartis Investigative Site | Hillerod | |
| Egypt | Novartis Investigative Site | Cairo | |
| France | Novartis Investigative Site | Angers | |
| France | Novartis Investigative Site | Avignon | |
| France | Novartis Investigative Site | Bobigny | |
| France | Novartis Investigative Site | Creteil | |
| France | Novartis Investigative Site | Lille Cedex | |
| France | Novartis Investigative Site | Lyon | |
| France | Novartis Investigative Site | Nice | |
| France | Novartis Investigative Site | Paris | |
| France | Novartis Investigative Site | Paris Cedex 14 | |
| France | Novartis Investigative Site | Pessac Cedex | |
| France | Novartis Investigative Site | Rennes | |
| France | Novartis Investigative Site | Toulouse Cedex | |
| France | Novartis Investigative Site | Vandoeuvre Les Nancy | |
| Germany | Novartis Investigative Site | Augsburg | |
| Germany | Novartis Investigative Site | Braunschweig | |
| Germany | Novartis Investigative Site | Dresden | |
| Germany | Novartis Investigative Site | Dusseldorf | |
| Germany | Novartis Investigative Site | Frankfurt | |
| Germany | Novartis Investigative Site | Frankfurt/Main | |
| Germany | Novartis Investigative Site | Frieburg | |
| Germany | Novartis Investigative Site | Gottingen | |
| Germany | Novartis Investigative Site | Greifswald | |
| Germany | Novartis Investigative Site | Hannover | |
| Germany | Novartis Investigative Site | Mainz | |
| Germany | Novartis Investigative Site | Muenchen | |
| Germany | Novartis Investigative Site | Ulm | |
| Greece | Novartis Investigative Site | Athens | |
| Greece | Novartis Investigative Site | Larissa | |
| Greece | Novartis Investigative Site | Patras | |
| Greece | Novartis Investigative Site | Thessaloniki | |
| Hong Kong | Novartis Investigative Site | Hong Kong | |
| Israel | Novartis Investigative Site | Afula | |
| Israel | Novartis Investigative Site | Jerusalem | |
| Israel | Novartis Investigative Site | Petach-Tikva | |
| Italy | Novartis Investigative Site | Bologna | |
| Italy | Novartis Investigative Site | Brindisi | |
| Italy | Novartis Investigative Site | Cagliari | |
| Italy | Novartis Investigative Site | Cona | |
| Italy | Novartis Investigative Site | Genova | |
| Italy | Novartis Investigative Site | Milano | |
| Italy | Novartis Investigative Site | Napoli | |
| Italy | Novartis Investigative Site | Orbassano | |
| Italy | Novartis Investigative Site | Palermo | |
| Italy | Novartis Investigative Site | Pavia | |
| Italy | Novartis Investigative Site | Pisa | |
| Italy | Novartis Investigative Site | Reggio Calabria | |
| Italy | Novartis Investigative Site | Roma | |
| Italy | Novartis Investigative Site | Sassari | |
| Korea, Republic of | Novartis Investigative Site | Seoul | |
| Lebanon | Novartis Investigative Site | Hazmiyeh | |
| Malaysia | Novartis Investigative Site | Kota Bahru | |
| Malaysia | Novartis Investigative Site | Kuala Lumpur | |
| Netherlands | Novartis Investigative Site | Nijmegen | |
| South Africa | Novartis Investigative Site | Johannesburg | |
| South Africa | Novartis Investigative Site | Parktown | |
| Spain | Novartis Investigative Site | Baracaldo | |
| Spain | Novartis Investigative Site | Barcelona | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Sevilla | |
| Spain | Novartis Investigative Site | Valencia | |
| Switzerland | Novartis Investigative Site | Geneve | |
| Switzerland | Novartis Investigative Site | Zurich | |
| Taiwan | Novartis Investigative Site | Taichung | |
| Taiwan | Novartis Investigative Site | Taipei | |
| Thailand | Novartis Investigative Site | Bangkok | |
| Thailand | Novartis Investigative Site | Chaingmai | |
| Turkey | Novartis Investigative Site | Adana | |
| Turkey | Novartis Investigative Site | Ankara | |
| Turkey | Novartis Investigative Site | Istanbul | |
| Turkey | Novartis Investigative Site | Izmir | |
| United Kingdom | Novartis Investigative Site | Leeds | |
| United Kingdom | Novartis Investigative Site | Leicester | |
| United Kingdom | Novartis Investigative Site | London | |
| United Kingdom | Novartis Investigative Site | Manchester | |
| United Kingdom | Novartis Investigative Site | Sheffield |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
Australia, Austria, Belgium, China, Denmark, Egypt, France, Germany, Greece, Hong Kong, Israel, Italy, Korea, Republic of, Lebanon, Malaysia, Netherlands, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | at baseline and at 52 weeks | ||
| Secondary | To evaluate the safety and tolerability profile of in patients treated for up to 52 weeks | Monthly | ||
| Secondary | Evaluate efficacy, tolerabilty and safety in the subgroup of patients with baseline LIC < 7 mg Fe/g dw | Monthly | ||
| Secondary | Evaluate the relationship between serum ferritin and potential surrogate markers | Monthly |