Condition category
Haematological Disorders
Date applied
23/07/2003
Date assigned
05/09/2003
Last edited
21/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Elliot Vichinsky

ORCID ID

Contact details

Children's Hospital & Research Center at Oakland
747 52nd Street
OPC-PCRC
1st Floor
Oakland
94609-1809
United States of America

Additional identifiers

EudraCT number

2004-000597-31

ClinicalTrials.gov number

NCT01090323

Protocol/serial number

CICL670 0109

Study information

Scientific title

A randomised, multicentre, open label, phase Il study to evaluate the safety, tolerability, pharmacokinetics and the effects on liver iron concentration of repeated doses of 10 mg/kg/day of ICL670 relative to deferoxamine in sickle cell disease (SCD) patients with transfusional haemosiderosis

Acronym

ICL109

Study hypothesis

The primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine.

Ethics approval

The trial was conducted in accordance with the Declaration of Helsinki. Institutional Review Board approval was obtained at each participating institution and written informed consent was obtained from all patients or guardians prior to participation in any study procedures.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Sickle cell disease (SCD)

Intervention

The study duration was 52 weeks. The initial 24 patients enroled were randomised to receive deferasirox 10 mg/kg or deferoxamine at recommended doses of 20 - 60 mg/kg based on initial liver iron concentration (LIC).

Subsequently, additional safety information became available for deferasirox suggesting a need to modify the starting dose. Therefore, following the enrolment of the first 24 patients, the study was amended so that all subsequent patients randomised to deferasirox were dosed at 10 - 30 mg/kg according to baseline LIC.

Deferasirox was given once daily each morning as a dispersed solution in water, half-an-hour before breakfast.

Deferoxamine was administered as a slow subcutaneous infusion over 8 - 12 hours using electronic Microject Chrono® (Medical Technology, Turin, Italy) infusion pumps on 5 - 7 days a week.

Intervention type

Drug

Phase

Phase II

Drug names

Deferasirox (ICL670), deferoxamine (DFO)

Primary outcome measures

Safety assessments:
1. Laboratory assessments: performed monthly and included complete blood counts with differential counts:
1.1. Biochemistry testing (electrolytes, glucose, liver function tests, gamma-glutaryl-transferase, lactate dehydrogenase, cholesterol, triglycerides, uric acid, total protein, C-reactive protein, copper and zinc level)
1.2. Iron parameters (total iron, transferrin, transferrin saturation and ferritin)
1.3. Urinary testing performed on random collections (determination of creatinine, total protein and albumin)
2. Physical examinations (electrocardiograms [ECG], audiometry and ophthalmological tests) were performed at baseline, 12, 24, 36 and 52 weeks
3. In patients less than 16 years of age, additional assessments included growth velocity and pubertal stage

Secondary outcome measures

Efficacy assessments:
1. Liver iron concentration: determined by superconducting quantum interference device (SQUID) biosusceptometry at baseline, 24 and 52 weeks
2. Serum ferritin: assessed monthly during the study and the change was determined using the baseline and final ferritin level

Compliance:
1. For deferasirox, compliance was assessed by counting the number of tablets returned in bottles at each visit
2. For deferoxamine, the numbers of vials returned at each visit were counted

Overall trial start date

01/01/2004

Overall trial end date

01/01/2006

Reason abandoned

Eligibility

Participant inclusion criteria

Patients with SCD requiring chronic blood transfusions to prevent complications (stroke, chest syndrome) and thus developing transfusional iron overload requiring chronic chelation therapy.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

195

Participant exclusion criteria

1. Serum creatinine above the upper limit of normal (ULN)
2. Significant proteinuria (as indicated by a urinary protein:creatinine ratio of greater than or equal to 0.5 confirmed at two visits)
3. Active hepatitis B or C:
3.1. Active hepatitis B defined as liver function tests above the normal range, together with a positive antigen (hepatitis B e antigen, hepatitis B surface antigen) test or positive immunoglobulin M (IgM) core antibody test in conjunction with a negative hepatitis B surface antibody test
3.2. Active hepatitis C defined as liver function tests above the normal range in the presence of a positive hepatitis C antibody test and detectable hepatitis C ribonucleic acid (RNA) levels
4. Second and third atrioventricular block
5. QT interval prolongation
6. Therapy with digoxin or similar medications (treatment with β-blockers or angiotensin-converting enzyme inhibitors was permitted)
7. Chelation therapy-associated ocular toxicity

Recruitment start date

01/01/2004

Recruitment end date

01/01/2006

Locations

Countries of recruitment

Canada, France, Italy, United Kingdom, United States of America

Trial participating centre

Children's Hospital & Research Center at Oakland
Oakland
94609-1809
United States of America

Sponsor information

Organisation

Novartis Pharmaceuticals Corporation (USA)

Sponsor details

One Health Plaza
East Hanover
07936
United States of America
+1 (0)862 778 2791
halyna.wysowskyj@pharma.novartis.com

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

Novartis Pharmaceuticals Corporation

Alternative name(s)

NPC

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United States of America

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

See https://clinicaltrials.gov/ct2/show/results/NCT01090323

Publication summary

2007 results in: http://www.ncbi.nlm.nih.gov/pubmed/17233848

Publication citations

  1. Results

    Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, Files B, Hassell K, Kelly P, Wilson F, Bernaudin F, Forni GL, Okpala I, Ressayre-Djaffer C, Alberti D, Holland J, Marks P, Fung E, Fischer R, Mueller BU, Coates T, , A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease., Br. J. Haematol., 2007, 136, 3, 501-508, doi: 10.1111/j.1365-2141.2006.06455.x.

Additional files

Editorial Notes

21/03/2016: added link to results - basic reporting.