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Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload (HYPERION)

Primary Purpose

Cardiac Iron Overload

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Deferasirox and Deferoxamine
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiac Iron Overload focused on measuring Cardiac iron overload,, deferasirox,, deferoxamine

Eligibility Criteria

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

Inclusion Criteria:

  • Patients with β-thalassemia major or Diamond-Blackfan anemia (DBA) or congenital sideroblastic anemia on chronic transfusion therapy
  • Myocardial T2* value that is ≥ 5 and < 10 ms
  • Left ventricular ejection fraction (LVEF) ≥ 56% as determined by Magnetic resonance imaging (MRI)
  • Liver Iron Concentration (LIC) ≥ 7 mg Fe /g dw as determined by R2 MRI.
  • Lifetime history of at least 50 units of red blood cell transfusions, and must be receiving at least ≥ 8 units/yr of red blood cell transfusions
  • Serum ferritin ≥ 1000 ng/mL

Exclusion Criteria:

  • Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias)
  • Patients unable to undergo study assessments including MRI
  • Patients with serum creatinine greater than Upper limit of normal ULN)range or with significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥1.0 mg/mg in a non-first void urine sample at baseline.

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deferasirox

Arm Description

Deferoxamine combination followed by Deferasirox monotherapy

Outcomes

Primary Outcome Measures

Change in Cardiac Iron Content From Baseline to Month 12
Cardiac T2* is the most sensitive and reproducible test in detecting myocardial iron load. A cardiac T2* value of <10 ms is defined as severe cardiac iron overload. Participants who do not have baseline T2* or do not have any post-baseline T2* are excluded from the analysis.

Secondary Outcome Measures

Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24
The number of evaluable participants at each visit were used as the denominator for the calculation of proportion at each visit.
Change in Cardiac Iron Content From Baseline to Month 6,18 and 24
The change in cardiac iron content was calculated as ratio of Cardiac T2* at different time points; the efficacy endpoint analyses were performed on the Full Analysis Set (FAS).
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24
Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24
Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Time to Achieve From Baseline (FAS) of at Least 10% at Month 24
Time from date of start of study treatment to date when first achieving T2* ≥ 10 ms (but at least 10% relative increase from baseline) was summarized using the reverse Kaplan-Meier estimates (1 - Kaplan-Meier estimates) for the FAS.
Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24
Cardiac iron concentration (mg Fe/g dw) was quantified using the formula (cardiac iron concentration (mg Fe/g dw) = 45 * T2* (ms) ^ (-1.22) and analyzed over time.

Full Information

First Posted
September 21, 2010
Last Updated
July 23, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01254227
Brief Title
Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload
Acronym
HYPERION
Official Title
Phase II, Open-label, Single-arm, Multicenter Study to Evaluate the Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Patients With Severe Cardiac Iron Overload Due to Chronic Blood Transfusion (HYPERION)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
January 2011 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
November 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
This study will evaluate the efficacy and safety of deferasirox in combination with deferoxamine followed be deferasirox monotherapy in patients with severe iron overload due to chronic blood transfusions.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cardiac Iron Overload
Keywords
Cardiac iron overload,, deferasirox,, deferoxamine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deferasirox
Arm Type
Experimental
Arm Description
Deferoxamine combination followed by Deferasirox monotherapy
Intervention Type
Drug
Intervention Name(s)
Deferasirox and Deferoxamine
Primary Outcome Measure Information:
Title
Change in Cardiac Iron Content From Baseline to Month 12
Description
Cardiac T2* is the most sensitive and reproducible test in detecting myocardial iron load. A cardiac T2* value of <10 ms is defined as severe cardiac iron overload. Participants who do not have baseline T2* or do not have any post-baseline T2* are excluded from the analysis.
Time Frame
From Baseline to Month 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With T2*>=10 ms and at Least 10% Relative Increase From Baseline at Month 6, 12, 18 and 24
Description
The number of evaluable participants at each visit were used as the denominator for the calculation of proportion at each visit.
Time Frame
From the Months 6, 12, 18 and 24
Title
Change in Cardiac Iron Content From Baseline to Month 6,18 and 24
Description
The change in cardiac iron content was calculated as ratio of Cardiac T2* at different time points; the efficacy endpoint analyses were performed on the Full Analysis Set (FAS).
Time Frame
From Baseline to Months 6, 18 and 24
Title
Change in Left Ventricular Ejection Fraction (LVEF) From Baseline to Month 6, 12, 18 and 24
Description
Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Time Frame
From the Months 6, 12, 18 and 24
Title
Change in Right Ventricular Ejection Fraction (RVEF) From Baseline to Month 6, 12, 18 and 24
Description
Magnetic resonance imaging (MRI)-measured cardiac T2* and cardiac function reflected by left and right ventricle ejection fraction. A standardized MRI protocol for T2* acquisition technique will be used in the centers. Images will be reviewed centrally by an expert MRI reader.
Time Frame
From the Months 6, 12, 18 and 24
Title
Time to Achieve From Baseline (FAS) of at Least 10% at Month 24
Description
Time from date of start of study treatment to date when first achieving T2* ≥ 10 ms (but at least 10% relative increase from baseline) was summarized using the reverse Kaplan-Meier estimates (1 - Kaplan-Meier estimates) for the FAS.
Time Frame
At 24 months
Title
Cardiac Iron Concentration Levels From Baseline and at Month 6, 12, 18 and 24
Description
Cardiac iron concentration (mg Fe/g dw) was quantified using the formula (cardiac iron concentration (mg Fe/g dw) = 45 * T2* (ms) ^ (-1.22) and analyzed over time.
Time Frame
From the Baseline, Month 6, 12, 18 and Month 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with β-thalassemia major or Diamond-Blackfan anemia (DBA) or congenital sideroblastic anemia on chronic transfusion therapy Myocardial T2* value that is ≥ 5 and < 10 ms Left ventricular ejection fraction (LVEF) ≥ 56% as determined by Magnetic resonance imaging (MRI) Liver Iron Concentration (LIC) ≥ 7 mg Fe /g dw as determined by R2 MRI. Lifetime history of at least 50 units of red blood cell transfusions, and must be receiving at least ≥ 8 units/yr of red blood cell transfusions Serum ferritin ≥ 1000 ng/mL Exclusion Criteria: Patients with clinical symptoms of cardiac dysfunction (shortness of breath at rest or exertion, orthopnea, exercise intolerance, lower extremity edema, arrhythmias) Patients unable to undergo study assessments including MRI Patients with serum creatinine greater than Upper limit of normal ULN)range or with significant proteinuria as indicated by a urinary protein/creatinine ratio (UPCR) ≥1.0 mg/mg in a non-first void urine sample at baseline. Other protocol-defined inclusion/exclusion criteria may apply
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
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Novartis Investigative Site
City
Cairo
Country
Egypt
Facility Name
Novartis Investigative Site
City
Athens
State/Province
GR
ZIP/Postal Code
GR-115 27
Country
Greece
Facility Name
Novartis Investigative Site
City
Patra - RIO
State/Province
GR
ZIP/Postal Code
265 04
Country
Greece
Facility Name
Novartis Investigative Site
City
Cagliari
State/Province
CA
ZIP/Postal Code
09121
Country
Italy
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16128
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80138
Country
Italy
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Novartis Investigative Site
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Novartis Investigative Site
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Novartis Investigative Site
City
Antalya
ZIP/Postal Code
07070
Country
Turkey
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Novartis Investigative Site
City
Izmir
ZIP/Postal Code
35040
Country
Turkey
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom

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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com.
IPD Sharing URL
https://www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
25934475
Citation
Aydinok Y, Kattamis A, Cappellini MD, El-Beshlawy A, Origa R, Elalfy M, Kilinc Y, Perrotta S, Karakas Z, Viprakasit V, Habr D, Constantinovici N, Shen J, Porter JB; HYPERION Investigators. Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload. Blood. 2015 Jun 18;125(25):3868-77. doi: 10.1182/blood-2014-07-586677. Epub 2015 May 1.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=12963
Description
link to the results

Learn more about this trial

Efficacy and Safety of Deferasirox in Combination With Deferoxamine Followed by Deferasirox Monotherapy in Severe Cardiac Iron Overload

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