Evaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT01090323
First received: March 15, 2010
Last updated: May 3, 2011
Last verified: May 2011

March 15, 2010
May 3, 2011
July 2004
July 2009   (final data collection date for primary outcome measure)
Number of Participants With Adverse Events After Start of ICL670 [ Time Frame: 0 - 60 months ] [ Designated as safety issue: Yes ]
Safety as assessed by the number of participants with adverse event or death after the start of ICL670.
To evaluate the long-term safety and tolerability profile of ICL670 in sickle cell disease patients with transfusional iron overload requiring chelation therapy [ Time Frame: 0 - 60 months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01090323 on ClinicalTrials.gov Archive Site
Change in Serum Ferritin From Start of ICL670 to End of Study [ Time Frame: 0 - 60 months ] [ Designated as safety issue: No ]
The main efficacy variable was change in serum ferritin in response to therapy with ICL670. Due to variability of serum ferritin, end of study was considered as the mean of at most the last 3 available observations after the start of ICL670.
  • To allow patients treated with either ICL670 or DFO satisfactorily completing the week 52 assessment of the core protocol ICL670A0109 to continue iron chelation therapy with ICL670 [ Time Frame: 0 - 60 months ] [ Designated as safety issue: No ]
  • Change in serum ferritin over time in response to therapy with ICL670 [ Time Frame: 0 60 months ] [ Designated as safety issue: No ]
  • To determine LIC by MRI in a subset of patients (Although it was specified as a secondary objective in the protocol, MRI data were not collected in the extension phase of the trial). [ Time Frame: 0 - 60 months ] [ Designated as safety issue: No ]
  • Determinations relative to iron metabolism (serum ferritin, total iron, transferrin and transferrin saturation) [ Time Frame: 0 - 60 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Evaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).
A One Year Open Label, Non-comparative Extension to a Randomized, Multicenter, Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration (LIC) of Repeated Doses of 5-30mg/kg/Day ICL670 Relative to Deferoxamine (DFO) in Sickle Cell Disease (SCD) Patients With Transfusional Hemosideresis (THS) [Amendment 3: Extension Prolonged to 4-years]

The safety, tolerability, effects on liver iron concentration and pharmacokinetics of ICL670 is studied in sickle cell disease patients with transfusional hemosiderosis.

The treatment period started once the patient completed the core study and signed informed consent. It is continued for up to 4 years. Safety parameters were assessed every 4 weeks. Eye and Ear examinations were performed on a yearly basis. To further investigate the extent of iron overload, serum ferritin, iron, and transferrin were monitored every four weeks. The Program Safety Board monitored the safety of ICL670 during the study to evaluate and categorize any serious case reported in association with ICL670.

Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Sickle Cell Disease
Drug: ICL670
Daily doses of ICL670 were taken orally 30 minutes before breakfast. The doses range from 5-40 mg/kg and were determined based on the patient's trend in serum ferritin over time during the core study (0109) and on the frequency of blood transfusions the patient received. The treatment duration was up to 4 years.
Experimental: ICL670
Intervention: Drug: ICL670
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
185
Not Provided
July 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

Patients were included who met the following criteria:

  • Completion of the core [Study 0109]
  • Serum ferritin greater than or equal to 500 µg/L
  • Ability to comply with all study-related procedures, medications, and evaluations
  • Sexually active post-menarche female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.
  • Written informed consent and assent by the patient and or their parents or legal guardian.

Additional inclusion criteria for pediatric patients The definition of the term 'pediatric' for enrollment and study conduct was in accordance with local law. Parents or the legal guardians were fully informed by the investigator as to the requirements of the study. The pediatric patients themselves were informed according to their capabilities in a language and terms that they were able to understand. Written informed consent was obtained from their legal guardian on the patient's behalf in accordance with national legislation. If capable, all patients had to also personally sign their written informed consent.

Exclusion Criteria:

Patients who met the following criteria were to be excluded:

  • History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
  • Serum creatinine above the age-appropriate upper limit of normal within one week prior to entry
  • Patients with ALT ≥ 500 U/L within one week prior to entry
  • Evidence of chelation-related cataracts or hearing loss within 4 weeks prior to baseline
  • Pregnancy (as indicated by serum β-HCG pregnancy test for all female patients with the potential to become pregnant) and patients who are breastfeeding
  • Patients treated with systemic investigational drug within 4 weeks prior to or with topical investigational drug within 7 days prior to the baseline visit

Other protocol-defined inclusion/exclusion criteria may apply

Both
2 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   France,   Italy,   United Kingdom
 
NCT01090323
CICL670A0109E1, EudraCT no. 2004-000597-31
Yes
External Affairs, Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP