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

NCT01818726 | Terminated Phase 4 Results DMC

• 1 other identifier: CICL670ARU02
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Aplastic Anemia

Keywords

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

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

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

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

Drug: No chelation

Interventions

ICL670 DRUG

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

Also known as: Deferasirox

Serum ferritin level ≥ 1,000 μg/l

Chelation DRUG

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).

Serum ferritin level ≥ 1,000 μg/l

No chelation DRUG

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

Serum ferritin level < 1,000 μg/l

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Moscow, 125167, Russia

Location

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Deferasirox; Chelating Agents

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sequestering Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2013
• First Posted: March 26, 2013
• Study Start: June 23, 2014
• Primary Completion: October 17, 2016
• Study Completion: October 17, 2016
• Last Updated: August 16, 2019
• Results First Posted: August 16, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share

Locations

RU (1)