An Extension Study of Iron Chelation Therapy With Deferasirox (ICL670) in β-thalassemia Patients With Transfusional Iron Overload

• ClinicalTrials.gov Identifier: NCT00171210
• Recruitment Status: Completed
• First Posted: September 15, 2005
• Results First Posted: May 2, 2011
• Last Update Posted: May 30, 2011
• Sponsor: Novartis Pharmaceuticals
• Information provided by: Novartis

Tracking Information

• First Submitted Date: September 12, 2005
• First Posted Date: September 15, 2005
• Results First Submitted Date: December 14, 2010
• Results First Posted Date: May 2, 2011
• Last Update Posted Date: May 30, 2011
• Study Start Date: October 2004
• Actual Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 31, 2011)

Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event [ Time Frame: up to 5 years ]

Adverse events results are based on preferred terms with at least 7% of participants in any group.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: May 24, 2011)

• Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by Liver Biopsy [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Mean absolute change of LIC from start of Deferasirox (ICL670) treatment to the end of study assessed by liver biopsy. Reported in milligrams of Iron per gram dry weight (mg Fe/g dw).
• Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by SQUID [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Mean absolute change in LIC from start of Deferasirox (ICL670) treatment to the end of the study assessed by Superconducting Quantum Interfering Device (SQUID) measurement used as a non-invasive alternative to Biopsy for pediatric participants. Reported in milligrams of Iron per gram dry weight (mg Fe/g dw).
• Long-term Effect of Treatment With ICL670 on the Changes in Serum Ferritin Levels From Start of ICL670 Treatment to End of Study [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Mean Absolute Change in serum ferritin (ug/L) from start of treatment with Deferasirox (ICL670) to end of study taking into account the therapeutic goal which will either be to maintain iron balance or to induce negative iron balance. End of study taken as the mean of, at most, the last three available results after start of treatment with ICL670.
• Change in Surrogate Marker: Serum Transferrin From Start of Treatment With ICL670 to End of Study [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Measurement of the relative change in percent of potential surrogate marker: Serum Transferrin (g/L) from start of treatment with Deferasirox (ICL670) to end of study. (Serum Transferrin at the End of Study-Serum Transferrin at Start of ICL670)/Serum Transferrin at Start of ICL670*100.
• Change in Surrogate Marker: Serum Iron From Start of Treatment With ICL670 to End of Study [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Measurement of the relative change of potential surrogate markers: Serum Iron (µmol/L) from start of treatment with Deferasirox (ICL670) to end of study. (Serum Iron at the End of Study-Serum Iron at Start of ICL670)/Serum Iron at Start of ICL670*100.
• Change in Surrogate Marker: Transferrin Saturation From Start of Treatment With ICL670 to End of Study [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Measurement of the relative change of potential surrogate marker: Transferrin Saturation (Percent) from start of treatment with Deferasirox (ICL670) to end of study. (Transferrin Saturation at the End of Study-Tranferrin Saturation at Start of ICL670)/Transferrin Saturation at Start of ICL670*100.
• Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Measurement of median absolute change in liver iron content (LIC) from start of treatment with Deferasirox (ICL670) to end of study obtained through biopsy. Absolute change = End of study value - start of treatment value. LIC is expressed in mg of iron per gram of liver dry weight (mg Fe/g dw).
• Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Relative change in liver iron content (LIC) as measured by biopsy and calculated by: End of study value - Start of ICL670 treatment value (absolute change) / Start of ICL670 treatment value.
• Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by SQUID [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Measurement of the median absolute change in liver iron content (LIC) from start of treatment with Deferasirox (ICL670) to end of study obtained through Superconducting Quantum Interfering Device (SQUID). Absolute change = End of study value - start of treatment value. LIC is expressed in mg of iron per gram of liver dry weight (mg Fe/g dw).
• Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study as Measured by SQUID [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Relative change in liver iron content (LIC) measured by Superconducting Quantum Interfering Device (SQUID), calculated by: End of study value - Start of ICL670 treatment value (absolute change) / Start of ICL670 treatment value.
• Change of Total Body Iron Excretion Rate (TBIE) From Start of ICL670 Treatment to the End of Study [ Time Frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) ]
  Median change in TBIE (mg/kg/day) from start of treatment with Deferasirox (ICL670) to end of study.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Extension Study of Iron Chelation Therapy With Deferasirox (ICL670) in β-thalassemia Patients With Transfusional Iron Overload
• Official Title: An Extension Study of Iron Chelation Therapy With Deferasirox (ICL670)in β-thalassemia Patients With Transfusional Iron Overload

Brief Summary

A 1-year randomized Phase III core trial (NCT00061750) using deferoxamine as the comparator was conducted to investigate the efficacy of deferasirox in regularly transfused patients with β-thalassemia 2 years of age and older. Patients who successfully completed this main trial may continue in this extension trial to receive chelation therapy with deferasirox for an additional 4 years.

The objective of this study is to assess the efficacy and long-term safety of deferasirox in regularly transfused patients with β-thalassemia 2 years of age and older.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Transfusional Iron Overload in β-thalassemia

Intervention

Drug: Deferasirox

Tablets taken orally once a day.

Study Arms

Experimental: Deferasirox

All participants received Deferasirox (ICL670) orally once a day. Dosage based on body weight.

Intervention: Drug: Deferasirox

• Publications *: Cappellini MD, Bejaoui M, Agaoglu L, Canatan D, Capra M, Cohen A, Drelichman G, Economou M, Fattoum S, Kattamis A, Kilinc Y, Perrotta S, Piga A, Porter JB, Griffel L, Dong V, Clark J, Aydinok Y. Iron chelation with deferasirox in adult and pediatric patients with thalassemia major: efficacy and safety during 5 years' follow-up. Blood. 2011 Jul 28;118(4):884-93. doi: 10.1182/blood-2010-11-316646. Epub 2011 May 31. Erratum In: Blood. 2011 Nov 3;118(18):5060.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 31, 2011): 506
• Original Enrollment: Not Provided
• Study Completion Date: Not Provided
• Actual Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria

• Patients who completed the 12-month core study (NCT00061750)
• Female patients after menarche and who were sexually active, if they used double-barrier contraception, oral contraceptive plus barrier contraceptive, or had undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation
• Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with the national legislation

Exclusion criteria

• Pregnant or breast feeding patients
• Patients with a history of non-compliance to medical regimens or those considered to be potentially unreliable

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belgium, Brazil, Canada, France, Germany, Greece, Italy, Tunisia, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT00171210
• Other Study ID Numbers: CICL670A0107E1
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: External Affairs, Novartis Pharmaceuticals
• Original Responsible Party: Not Provided
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Novartis
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: May 2011