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
Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients
Sponsors
Source
Novartis
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
Brief Summary
To evaluate 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.
Overall Status
Completed
Start Date
2014-06-23
Completion Date
2016-10-17
Primary Completion Date
2016-10-17
Phase
Phase 4
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Change of serum ferritin, iron transferrin saturation, serum total iron-binding capacity (TIBC) |
Screening, 4,8,12,16,20,24,28,32,36,40,44,48,52 weeks |
Secondary Outcome
Measure |
Time Frame |
|
Adverse events |
52 weeks |
|
Change of proteinuria in urinalysis over a period of 1 year treatment. |
1,2,3,4,8,12,16,20,24,28,32,36,40,44,48,52 weeks |
|
Change from baseline in creatinine clearance over a period of 1 year treatment. |
1,2,3,4,8,12,16,20,24,28,32,36,40,44,48,52 weeks |
|
Change from baseline of serum creatinine, bilirubin, ALT, AST, glucose over a period of 1 year treatment. |
1,2,3,4,8,12,16,20,24,28,32,36,40,44,48,52 weeks |
Enrollment
14
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
In the investigational arm all patients recieve a standard immunosuppressant (Cyclosporine A). The starting dose of Exjade will be 20 mg/kg/day with up- and down-titration steps of 5-10 mg/kg/day if necessary, depending on serum ferritin, tolerability and comorbidities. Doses above 30 mg/kg are discouraged as such experience is limited in aplastic anemia. Patients are to take Exjade once daily at least 30 minutes before meals, on the same time each day. A combination of 250 mg and 500 mg tablets may be used to provide a specific dose level. The duration of treatment in this study is 12 months. The investigator muct emphasize complaince and will instruct the patients to take the Exjade exactly as prescribe.
Arm Group Label
Exjade treatment arm
Other Name
Deferasirox and standard immunosupressive therapy
Intervention Type
Drug
Intervention Name
Description
Comparative group of patients with aplastic anemia and transfusion-dependent iron overload is undergoing treatment programs of standard immunosuppressive treatment ( immunosupressant -Cyclosporine A)
Arm Group Label
Conventional treatment arm
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.
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Novartis Pharmaceuticals |
Study Director |
Novartis Pharmaceuticals |
Location
Facility |
|
Novartis Investigative Site Moscow 125167 Russian Federation |
Location Countries
Country
Russian Federation
Verification Date
2017-08-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keyword
Has Expanded Access
No
Condition Browse
Number Of Arms
2
Intervention Browse
Mesh Term
Cyclosporins
Cyclosporine
Immunosuppressive Agents
Deferasirox
Arm Group
Arm Group Label
Conventional treatment arm
Arm Group Type
Active Comparator
Description
10 Adult (aged above 18) transfusion-dependent patients with AA and serum ferritin < 1000 mg/L undergoing treatment programs of immunosuppressive treatment (Cyclosporine A)
Arm Group Label
Exjade treatment arm
Arm Group Type
Experimental
Description
15 transfusion-dependent adult (aged above 18) patients with AA and serum ferritin ≥ 1000 mg/L undergoing treatment programs of immunosuppressive treatment (Cyclosporine A) and Exjade
Firstreceived Results Date
N/A
Patient Data
Sharing Ipd
Undecided
Ipd 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
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
March 5, 2013
Study First Submitted Qc
March 25, 2013
Study First Posted
March 26, 2013
Last Update Submitted
August 25, 2017
Last Update Submitted Qc
August 25, 2017
Last Update Posted
August 28, 2017
ClinicalTrials.gov processed this data on August 29, 2018
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.