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

Cardiac Iron Overload Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01254227
• Other study ID #: CICL670A2214
• Secondary ID: 2010-021062-29
• Status: Completed
• Phase: Phase 2
• Start date: January 2011
• Est. completion date: November 2013

Study information

• Verified date: July 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years and older

Eligibility

Inclusion Criteria:

• Patients with ß-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

Related Conditions & MeSH terms

• Cardiac Iron Overload
• Iron Overload

Intervention

Drug:
• Deferasirox and Deferoxamine

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Toronto	Ontario
Egypt	Novartis Investigative Site	Cairo
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Patra - RIO	GR
Italy	Novartis Investigative Site	Cagliari	CA
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Napoli
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Turkey	Novartis Investigative Site	Adana
Turkey	Novartis Investigative Site	Antalya
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
United Kingdom	Novartis Investigative Site	London

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Canada,  Egypt,  Greece,  Italy,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From Baseline to Month 12
Secondary	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.	From the Months 6, 12, 18 and 24
Secondary	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).	From Baseline to Months 6, 18 and 24
Secondary	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.	From the Months 6, 12, 18 and 24
Secondary	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.	From the Months 6, 12, 18 and 24
Secondary	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.	At 24 months
Secondary	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.	From the Baseline, Month 6, 12, 18 and Month 24

External Links

•   link to the results