Extended Evaluation of Deferasirox Film-coated Tablet (FCT) Formulation

Open-label, Multicenter, Single Arm, Phase III Study to Collect Additional Safety and Efficacy Data With Deferasirox Film-coated Tablets in Patients Completing Study CICL670F2201

Extend evaluation of deferasirox film-coated tablet (FCT) formulation

Study Overview

• Status: Completed
• Conditions: Chronic Iron Overload
• Intervention / Treatment: Drug: Deferasirox

Detailed Description

Collection of additional safety and efficacy data with deferasirox film-coated tablet (FCT) in patients who had completed study CICL670F2201

• Provide patients who completed 24 weeks of treatment in the core study, CICL670F2201, the possibility to have additional treatment with the deferasirox FCT.
• Collect additional longer term data on the safety and the tolerability of the deferasirox FCT.
• Collect efficacy data on the deferasirox FCT in reduction or maintenance of iron burden as measured by serum ferritin level.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1140
    • Novartis Investigative Site
• Greece
  • Patras, Greece, 265 00
    • Novartis Investigative Site
  • Thessaloniki, Greece, 54642
    • Novartis Investigative Site
  • GR
    • Goudi-Athens, GR, Greece, 115 27
      • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80138
    • Novartis Investigative Site
  • CT
    • Catania, CT, Italy, 95125
      • Novartis Investigative Site
  • FE
    • Cona, FE, Italy, 44100
      • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16128
      • Novartis Investigative Site
  • ITA
    • Cagliari, ITA, Italy, 09121
      • Novartis Investigative Site
  • LE
    • Lecce, LE, Italy, 73100
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
  • PA
    • Palermo, PA, Italy, 90127
      • Novartis Investigative Site
    • Palermo, PA, Italy, 90146
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria for subjects:

• Completed 24-weeks of study treatment as described in the core protocol (CICL670F2201).
• Were deemed to have tolerated deferasirox treatment by the investigator.
• Provided written informed consent/assent before any study-specific procedures were performed. For pediatric patients, consent was obtained from parent(s) or legal patient's representative. Investigators were to have also obtained assent of patients according to local, regional or national guidelines.

Key Exclusion for subjects:

The exclusion criteria followed those described for the core protocol CICl670F2201, which were as follows:

• Creatinine clearance below the contraindication limit in the locally approved prescribing information.
• Serum creatinine > 1.5 × upper limit of normal range (ULN) at Screening
• Alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) > 5 × ULN,
• Significant proteinuria
• Patients with significant impaired gastrointestinal function or gastrointestinal disease
• Clinical or laboratory evidence of active Hepatitis B or Hepatitis C
• Patients with psychiatric or addictive disorders
• Patients with a known history of HIV seropositivity (Elisa or Western blot).
• History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there was an evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.
• Patients with a history of hypersensitivity to any of the study drug or excipients.
• Patients with significant medical condition that could interfere with the ability to participate in this study
• Patients who were participating in another clinical trial or receiving an investigational drug.
• Patients using prohibited medication,
• Patients with liver disease with severity of Child-Pugh Class B or C.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they were using effective methods of contraception during dosing of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Deferasirox; Treatment will be administered daily for up to 24 months. For each patient the daily dose is calculated based on the patient's actual body weight.	Drug: Deferasirox; Deferasirox FCT will be provided as 90 mg, 180 mg and 360 mg film-coated tablets for oral use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overview of Number of Participants With Adverse Events	Numbers represent counts of participants within the categories. An adverse event (AE) was defined as treatment emergent if its onset date is on or after (≥) the first administration of study treatment within this study or events present prior to start of study treatment but increased in severity on or after (≥) the first administration of study treatment within this study but not later than 30 days after the last study treatment in this study	Baseline up to approximately 25 months
Change From Baseline Red Blood Cells (RBC) (10^12 Cells/L) at Month 6 and Month 12	The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline	Baseline, 6 and 12 months
Change From Baseline White Blood Cells (WBC) (10^9 Cells/L) at Month 6 and Month 12	The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline	Baseline, 6 and 12 months
Change From Baseline Platelets (10^9 Cells/L) at Month 6 and Month 12	The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline	Baseline, 6 and 12 months
Change From Baseline Serum Creatinine (Umol/L) at Month 6 and Month 12	The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline	Baseline, 6 and 12 months
Change From Baseline Creatinine Clearance (mL/Min) at Month 6 and Month 12	The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline	Baseline, 6 and 12 months
Change From Baseline Alanine Aminotransferase/Serum Glutamic Pyruvic Transaminase (ALT/SGPT) (U/L) at Month 6 and Month 12	The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline	Baseline, 6 and 12 months
Change From Baseline Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) (U/L) at Month 6 and Month 12	The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline	Baseline, 6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline of Serum Ferritin Level (ug/L) at Month 6 and 12	The change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Change = Post - Baseline. A negative change from baseline is regarded as an improvement in this study	Baseline, 6 and 12 months
Percentage Relative Change From Baseline of Serum Ferritin (%) at Month 6 and 12	The percentage relative change from baseline at each time point is calculated only for subjects with a value at baseline and the particular time point. Post = Post baseline, Percentage relative change = 100 × ([Post - Baseline] / Baseline). Percentage relative change is calculated for each patient individually and then overall descriptive summary statistics is obtained for subjects with a value at baseline and the particular time point. A negative percentage relative change from baseline is regarded as an improvement in this study	Baseline, 6 and 12 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Tartaglione I, Origa R, Kattamis A, Pfeilstocker M, Gunes S, Crowe S, Fagan N, Vincenzi B, Ruffo GB. Two-year long safety and efficacy of deferasirox film-coated tablets in patients with thalassemia or lower/intermediate risk MDS: phase 3 results from a subset of patients previously treated with deferasirox in the ECLIPSE study. Exp Hematol Oncol. 2020 Aug 10;9:20. doi: 10.1186/s40164-020-00174-2. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 16, 2016
• Primary Completion (ACTUAL): July 23, 2019
• Study Completion (ACTUAL): July 23, 2019

Study Registration Dates

• First Submitted: March 21, 2016
• First Submitted That Met QC Criteria: March 25, 2016
• First Posted (ESTIMATE): March 28, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 3, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: adult; Deferasirox; MDS; Thalassemia; Myelodysplastic Syndrome; Iron overload; ICL670; Chelation; pediatric,; anemia.; Film coated tablet
• Additional Relevant MeSH Terms: Metabolic Diseases; Iron Metabolism Disorders; Iron Overload; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670AIC04

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 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No