Aplastic AnemiaPhase 4NCT01818726

Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients

A Phase 4 study testing ICL670, Chelation and No chelation in people with Aplastic Anemia, run by Novartis Pharmaceuticals at 1 site in Russia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Evaluated Exjade efficacy and safety in patients with aplastic anemia and transfusion-dependent iron overload, undergoing treatment programs of immunosuppressive treatment (Cyclosporine A) , in comparison with a group of patients undergoing treatment programs of immunosuppressive treatment (Cyclosporine A) without… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Aplastic Anemia
What is being tested?: ICL670, Chelation and No chelation
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteRussia
Study dates: 23 Jun 2014to 17 Oct 2016
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Main diagnosis: aplastic anemia
Absence of severe and/or uncontrolled comorbidities
Confirmed iron overload (serum ferritin ≥ 1000 mkg/L)
Serum creatinine is not higher than the upper limit of normal for the given age
Absence of severe proteinuria. Protein/Creatinine ratio should be < 0.5 mg/mg
Liver enzymes are < 5 ULN
Completion of a scheduled cycle of immunosuppressive treatment program, with no severe infectious or generalized hemorrhagic complications
WHO (ECOG) performance status ≤ 2

Who cannot join

No signed informed consent form
Patient is under 18 years old
Severe concomitant condition
Severe infectious and generalized haemorrhagic complication following regular planned cycle of programmed immune suppressive treatment.
History of increased sensitivity to active substance and any other ingredient of the medicinal product.
Creatinine clearance (CC) < 60 ml/min and/or creatinine concentration in blood serum is 2 or more times higher than upper limit of age normal by results of 2 tests at Visits 1 and 2.

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Severe liver disorders (class C by Child-Pugh scale).
Patients with aplastic anaemia in which chelator treatment will be ineffective due to rapid progression of the disease.
Significant proteinuria basing on protein creatinine ratio > 1.0 mg/ml in urine sample from second urination at Visits 1 and 2 (or as an alternative in 2 of 3 urine samples at screening);
Rare hereditary disorders related to galactose intolerance, severe deficit of lactase or glucose-galactose malabsorption;
Pregnancy, lactation;
Level of liver enzymes higher than 5 upper limits of age normal at Visits 1 and 2.

Trial locations and contacts

1 site in 1 country.

Russia1 site

Novartis Investigative Site
Moscow, 125167

Other trials in Russia

About this study

Official title: Open-label Study of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients Undergoing Treatment Programs in Comparison With Control Group

Read the detailed description

The secondary endpoints that were originally planned for this study were not analyzed as the study ended prematurely.

Conditions: Aplastic Anemia
Being tested: ICL670, Chelation, No chelation
Keywords: Aplastic anemia, deferasirox, ICL670, renal function, transfusion-dependent iron overload, immunosuppressive treatment, Cyclosporine A, unosuppressive treatment without chelation therapy
Medical subject headings: Anemia, Aplastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ICL670Drug
Also called Deferasirox
ICL670 was supplied in registered packages as 250mg or 500mg dispersible tablets.
ChelationDrug
Main group of patients with aplastic anemia and transfusion-dependent iron overload underwent treatment programs of standard immunosuppressive treatment (immunosupressant - Cyclosporine A) and received chelation with ICL670 (deferasirox).
No chelationDrug
Comparative group of patients with aplastic anemia and transfusion-dependent iron overload underwent treatment programs of standard immunosuppressive treatment ( immunosupressant -Cyclosporine A)

Study groups in NCT01818726
Study group	Role	What they receive
Serum ferritin level ≥ 1,000 μg/l	Experimental	Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study Receives: Drug: ICL670; Drug: Chelation
Serum ferritin level < 1,000 μg/l	Experimental	Transfusion-dependent adult patients with AA and serum ferritin < 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product Receives: Drug: No chelation

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Serum Ferritin Values
Change from baseline was be summarized descriptively for all on-treatment study visits.
Changes to the planned statistical analysis were related to significant withdrawal of patients from the Per-Protocol Analysis Set due to a large number of patients who discontinued the study (lack of assessments of iron exchange parameters at visits) and deviations from the Protocol affecting the assessment of efficacy parameters. Because of that, the additional efficacy analysis in the Per-Protocol Analysis Set was not performed.
Measured: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52
Change in Transferrin Saturation With Iron (TSI) Values
Mean percentage change from baseline in transferrin saturation with iron was summarized descriptively for all on-treatment study visits.
Measured: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52
Change in Serum Total Iron-binding Capacity (TIBC)
Mean change from baseline in serum total iron-binding capacity was summarized descriptively for all on-treatment study visits.
Measured: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 Jun 201417 Oct 2016

First posted26 Mar 2013 (estimated)
Study start23 Jun 2014
Primary completion17 Oct 2016
Study completion17 Oct 2016

Why it stopped: Failure to meet the schedule of patient recruitment

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01818726
Sponsor's protocol ID: CICL670ARU02
Status last verified: Jul 2019
First submitted: 5 Mar 2013
Last updated: 16 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Aplastic Anemia trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Open-label Study of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients Undergoing Treatment Programs in Comparison With Control Group
ClinicalTrials.gov ID: NCT01818726
Acronym / sponsor ID: CICL670ARU02
Conditions: Aplastic Anemia
Keywords: Aplastic anemia, deferasirox, ICL670, renal function, transfusion-dependent iron overload, immunosuppressive treatment, Cyclosporine A, unosuppressive treatment without chelation therapy
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Failure to meet the schedule of patient recruitment
Enrolment: 15 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 23 Jun 2014 (actual)
Primary completion: 17 Oct 2016 (actual)
Study completion: 17 Oct 2016 (actual)
First posted: 26 Mar 2013 (estimated)
Results: Posted 16 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The secondary endpoints that were originally planned for this study were not analyzed as the study ended prematurely.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Serum ferritin level ≥ 1,000 μg/l	Experimental	Drug: ICL670, Drug: ChelationTransfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study
Serum ferritin level < 1,000 μg/l	Experimental	Drug: No chelationTransfusion-dependent adult patients with AA and serum ferritin < 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Main diagnosis: aplastic anemia
Absence of severe and/or uncontrolled comorbidities
Confirmed iron overload (serum ferritin ≥ 1000 mkg/L)
Serum creatinine is not higher than the upper limit of normal for the given age
Absence of severe proteinuria. Protein/Creatinine ratio should be < 0.5 mg/mg

Key exclusion criteria (12 listed)

No signed informed consent form
Patient is under 18 years old
Severe concomitant condition
Severe infectious and generalized haemorrhagic complication following regular planned cycle of programmed immune suppressive treatment.
History of increased sensitivity to active substance and any other ingredient of the medicinal product.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
ICL670Also: DeferasiroxICL670 was supplied in registered packages as 250mg or 500mg dispersible tablets.	Drug	Serum ferritin level ≥ 1,000 μg/l
ChelationMain group of patients with aplastic anemia and transfusion-dependent iron overload underwent treatment programs of standard immunosuppressive treatment (immunosupressant - Cyclosporine A) and received chelation with ICL670 (deferasirox).	Drug	Serum ferritin level ≥ 1,000 μg/l
No chelationComparative group of patients with aplastic anemia and transfusion-dependent iron overload underwent treatment programs of standard immunosuppressive treatment ( immunosupressant -Cyclosporine A)	Drug	Serum ferritin level < 1,000 μg/l

Primary outcome

Change in Serum Ferritin Values
Time frame: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52
Change from baseline was be summarized descriptively for all on-treatment study visits. Changes to the planned statistical analysis were related to significant withdrawal of patients from the Per-Protocol Analysis Set due to a large number of patients who discontinued the study (lack of assessments of iron exchange parameters at visits) and deviations from the Protocol affecting the assessment of efficacy parameters. Because of that, the additional efficacy analysis in the Per-Protocol Analysis Set was not performed.
Change in Transferrin Saturation With Iron (TSI) Values
Time frame: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52
Mean percentage change from baseline in transferrin saturation with iron was summarized descriptively for all on-treatment study visits.
Change in Serum Total Iron-binding Capacity (TIBC)
Time frame: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52
Mean change from baseline in serum total iron-binding capacity was summarized descriptively for all on-treatment study visits.

Results and safety

Results posted to the registry on 16 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Serum Ferritin Level ≥ 1,000 μg/l	10	4
Serum Ferritin Level < 1,000 μg/l	5	3

Primary outcome: Change in Serum Ferritin Values

Time frame: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52. Mean (Standard Deviation). Unit: ng/ml

Measure	Serum Ferritin Level ≥ 1,000 μg/l n = 10	Serum Ferritin Level < 1,000 μg/l n = 5
Screening	2866.14 (1460.13)	769.02 (230.36)
Week 0	2895.62 (1245.81)	727.68 (299.61)
Week 4	2089.62 (638.29)	640.75 (292.14)
Week 8	2498.58 (1165.94)	623.14 (223.27)
Week 12	2262.12 (916.65)	653.62 (311.72)
Week 16	2164.01 (886.93)	647.58 (225.28)
Week 20	2054.23 (729.14)	646.80 (147.73)
Week 24	1710.67 (653.13)	680.08 (182.24)

Population analysed: Full Analysis Set included all patients of the Safety Analysis Set with available baseline data \& data obtained at follow-up visits \&/or final visit, for evaluation of at least 1 efficacy parameter. Statistical analysis was not performed due to large number of patients discontinuing \& thus lack of assessments of iron exchange parameters at visits.

Primary outcome: Change in Transferrin Saturation With Iron (TSI) Values

Time frame: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52. Mean (Standard Deviation). Unit: Percentage of saturation

Measure	Serum Ferritin Level ≥ 1,000 μg/l n = 10	Serum Ferritin Level < 1,000 μg/l n = 5
Screening	88.80 (10.01)	53.70 (10.28)
Week 0	87.19 (10.49)	54.88 (14.50)
Week 4	73.37 (8.55)	50.10 (14.14)
Week 8	72.68 (9.49)	49.54 (17.12)
Week 12	72.43 (5.98)	49.04 (10.15)
Week 16	68.60 (9.21)	52.78 (9.21)
Week 20	68.14 (19.64)	50.65 (11.45)
Week 24	74.30 (11.79)	5.90 (5.59)

Population analysed: Full Analysis Set (FAS) included all patients of the Safety Analysis Set with the available baseline data, as well as data obtained at follow-up visits and/or the final visit, for evaluation of at least one efficacy parameter.

Primary outcome: Change in Serum Total Iron-binding Capacity (TIBC)

Time frame: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52. Mean (Standard Deviation). Unit: μmol/l

Measure	Serum Ferritin Level ≥ 1,000 μg/l n = 10	Serum Ferritin Level < 1,000 μg/l n = 5
Screening	4.51 (9.34)	66.68 (14.95)
Week 0	49.98 (10.17)	49.10 (5.73)
Week 4	78.70 (20.93)	49.00 (4.95)
Week 8	73.90 (10.97)	47.44 (5.09)
Week 12	83.56 (19.86)	47.20 (4.68)
Week 16	85.31 (23.12)	49.53 (8.03)
Week 20	74.34 (18.95)	48.63 (4.46)
Week 24	81.90 (27.17)	46.53 (5.82)

Adverse events

Time frame: Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 376 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Serum Ferritin Level ≥ 1,000 μg/l	0 of 10 (0%)	4 of 10 (40%)	0 of 10
Serum Ferritin Level < 1,000 μg/l	0 of 5 (0%)	0 of 5 (0%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing ICL670, Chelation and No chelation in people with Aplastic Anemia, run by Novartis Pharmaceuticals at 1 site in Russia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Serum Ferritin Values (time frame: Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01818726.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2019.