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

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)

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.

Study Overview

• Status: Completed
• Conditions: Cardiac Iron Overload
• Intervention / Treatment: Drug: Deferasirox and Deferoxamine

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Novartis Investigative Site
• Egypt
  • Cairo, Egypt
    • Novartis Investigative Site
• Greece
  • GR
    • Athens, GR, Greece, GR-115 27
      • Novartis Investigative Site
    • Patra - RIO, GR, Greece, 265 04
      • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80138
    • Novartis Investigative Site
  • CA
    • Cagliari, CA, Italy, 09121
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16128
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
• Turkey
  • Adana, Turkey, 01330
    • Novartis Investigative Site
  • Antalya, Turkey, 07070
    • Novartis Investigative Site
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, NW1 2BU
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Deferasirox; Deferoxamine combination followed by Deferasirox monotherapy	Drug: Deferasirox and Deferoxamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• link to the results

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: September 21, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Actual): July 26, 2021
• Last Update Submitted That Met QC Criteria: July 23, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Cardiac iron overload,; deferasirox,; deferoxamine
• Additional Relevant MeSH Terms: Metabolic Diseases; Iron Metabolism Disorders; Iron Overload; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Siderophores; Deferasirox; Deferoxamine
• Other Study ID Numbers: CICL670A2214; 2010-021062-29 (EudraCT Number)

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 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.