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

NCT00631163 | Completed Phase 2 Results

• 2 other identifiers: CICL670A22042006-003337-32
• Study Type: interventional
• Target: 102
• Locations: 5 countries
• Sites: 31

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.

Conditions

Chronic Anemia; Transfusional Hemosiderosis

Keywords

Iron Overload,; Chelation,; MDS,; Chronic Anemia,; Deferasirox,; Transfusional hemosiderosis,

Outcome Measures

Primary Outcomes (1)

• Absolute Change From Baseline in Liver Iron Concentration (LIC) to Year 1

  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.

  From the Baseline, Year 1 (End of core study)

Secondary Outcomes (8)

• 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)

• 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)

• Absolute Change From Baseline in Serum Ferritin Levels to Year 2

  From the Baseline up to Year 2 (End of extension study)

• Absolute Serum Ferritin Levels Over 2 Years

  From the Baseline, Year 1 (End of core study), Year 2 (End of extension study)

• 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)

Study Arms (1)

Deferasirox

EXPERIMENTAL

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)

Interventions

Deferasirox (ICL670) DRUG

The recommended initial daily dose of Deferasirox is 20 mg/kg body weight.

Also known as: ICL670

Deferasirox

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (31)

Novartis Investigative Site

Nagoya, Aichi-ken, 453-8511, Japan

Location

Novartis Investigative Site

Nagoya, Aichi-ken, 466-8560, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 814-0180, Japan

Location

Novartis Investigative Site

Sapporo, Hokkaido, 060-8543, Japan

Location

Novartis Investigative Site

Nishinomiya, Hyōgo, 663-8501, Japan

Location

Novartis Investigative Site

Kahoku-gun, Ishikawa-ken, 920-0293, Japan

Location

Novartis Investigative Site

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Novartis Investigative Site

Sayama, Osaka, 589-8511, Japan

Location

Novartis Investigative Site

Suita, Osaka, 565-0871, Japan

Location

Novartis Investigative Site

Shimotsuka-gun, Tochigi, 321-0293, Japan

Location

Novartis Investigative Site

Simotsuke-city, Tochigi, 329-0498, Japan

Location

Novartis Investigative Site

Bunkyo-ku, Tokyo, 113-8655, Japan

Location

Novartis Investigative Site

Cyuo-ku, Tokyo, 104-8560, Japan

Location

Novartis Investigative Site

Minato-ku, Tokyo, 108-8639, Japan

Location

Novartis Investigative Site

Shinagawa-ku, Tokyo, 141-8625, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 160-0023, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 162-8666, Japan

Location

Novartis Investigative Site

Hiroshima, 734-8551, Japan

Location

Novartis Investigative Site

Kumamoto, 860-0811, Japan

Location

Novartis Investigative Site

Kyoto, 606-8507, Japan

Location

Novartis Investigative Site

Nagasaki, 852-8501, Japan

Location

Novartis Investigative Site

Toyama, 930-8550, Japan

Location

Novartis Investigative Site

Warsaw, 02-097, Poland

Location

Novartis Investigative Site

Warsaw, 02-776, Poland

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Valencia, 46026, Spain

Location

Novartis Investigative Site

Adana, 01330, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35040, Turkey (Türkiye)

Location

Related Publications (1)

• Kohgo Y, Urabe A, Kilinc Y, Agaoglu L, Warzocha K, Miyamura K, Lim LC, Glaser S, Wang C, Wiktor-Jedrzejczak W. Deferasirox Decreases Liver Iron Concentration in Iron-Overloaded Patients with Myelodysplastic Syndromes, Aplastic Anemia and Other Rare Anemias. Acta Haematol. 2015;134(4):233-42. doi: 10.1159/000381893.

  PMID: 26138856 RESULT

Related Links

• CICL670A2204 Results at Novartis Clinical Trials Results Website

MeSH Terms

Conditions

Iron Overload

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis Pharmaceuticals

  Novartis Pharmeceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2008
• First Posted: March 7, 2008
• Study Start: October 1, 2007
• Primary Completion: January 1, 2011
• Study Completion: February 1, 2012
• Last Updated: June 29, 2021
• Results First Posted: June 29, 2021

Record last verified: 2021-06

Locations

JP (22); PL (2); SG (1); TU (4); ES (2)