Back to results

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

Primary Purpose

Aplastic Anemia

Status

Terminated

Phase

Phase 4

Locations

Russian Federation

Study Type

Interventional

Intervention

ICL670

Chelation

No chelation

About this trial

This is an interventional treatment trial for Aplastic Anemia focused on measuring Aplastic anemia, deferasirox, ICL670, renal function, transfusion-dependent iron overload, immunosuppressive treatment, Cyclosporine A, unosuppressive treatment without chelation therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.
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.

Sites / Locations

Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Serum ferritin level ≥ 1,000 μg/l

Serum ferritin level < 1,000 μg/l

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01818726

First Posted

March 5, 2013

Last Updated

July 8, 2019

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01818726

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2019

Overall Recruitment Status

Terminated

Why Stopped

Failure to meet the schedule of patient recruitment

Study Start Date

June 23, 2014 (Actual)

Primary Completion Date

October 17, 2016 (Actual)

Study Completion Date

October 17, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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 chelation therapy.

Detailed Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aplastic Anemia

Keywords

Aplastic anemia, deferasirox, ICL670, renal function, transfusion-dependent iron overload, immunosuppressive treatment, Cyclosporine A, unosuppressive treatment without chelation therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Serum ferritin level ≥ 1,000 μg/l

Arm Type

Experimental

Arm Description

Arm Title

Serum ferritin level < 1,000 μg/l

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

ICL670

Other Intervention Name(s)

Deferasirox

Intervention Description

ICL670 was supplied in registered packages as 250mg or 500mg dispersible tablets.

Intervention Type

Drug

Intervention Name(s)

Chelation

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

No chelation

Intervention Description

Comparative group of patients with aplastic anemia and transfusion-dependent iron overload underwent treatment programs of standard immunosuppressive treatment ( immunosupressant -Cyclosporine A)

Primary Outcome Measure Information:

Title

Change in Serum Ferritin Values

Description

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

Title

Change in Transferrin Saturation With Iron (TSI) Values

Description

Mean percentage change from baseline in transferrin saturation with iron was summarized descriptively for all on-treatment study visits.

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

Title

Change in Serum Total Iron-binding Capacity (TIBC)

Description

Mean change from baseline in serum total iron-binding capacity was summarized descriptively for all on-treatment study visits.

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

125167

Country

Russian Federation

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs