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

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

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.

Study Overview

• Status: Terminated
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: ICL670; Drug: Chelation; Drug: No chelation

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 125167
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Serum ferritin level ≥ 1,000 μg/l; 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	Drug: ICL670; ICL670 was supplied in registered packages as 250mg or 500mg dispersible tablets.; Other Names: Deferasirox; Drug: Chelation; 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).
Experimental: Serum ferritin level < 1,000 μg/l; 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	Drug: No chelation; Comparative group of patients with aplastic anemia and transfusion-dependent iron overload underwent treatment programs of standard immunosuppressive treatment ( immunosupressant -Cyclosporine A)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2014
• Primary Completion (Actual): October 17, 2016
• Study Completion (Actual): October 17, 2016

Study Registration Dates

• First Submitted: March 5, 2013
• First Submitted That Met QC Criteria: March 25, 2013
• First Posted (Estimate): March 26, 2013

Study Record Updates

• Last Update Posted (Actual): August 16, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: deferasirox; renal function; Cyclosporine A; Aplastic anemia; ICL670; transfusion-dependent iron overload; immunosuppressive treatment; unosuppressive treatment without chelation therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Bone Marrow Diseases; Hematologic Diseases; Iron Metabolism Disorders; Bone Marrow Failure Disorders; Iron Overload; Anemia; Anemia, Aplastic; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670ARU02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No