Open-label, Multicenter Study Assessing Preference for Deferasirox Film-coated Tablet Compared to Dispersible Tablet

NCT ID: NCT02993224

Last Updated: 2021-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 148 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-27
• Study Completion Date: 2021-03-11

Brief Summary

Study to evaluate patient preference of deferasirox film-coated tablet (FCT) or deferasirox dispersible tablet (DT) in patient with transfusion - dependent thalassemia or non-transfusion -dependent thalassemia as measured by preference questionnaire at Week 48

Detailed Description

This was an open-label, multicenter, single arm, phase II study aimed at collecting data on preference for iron chelation therapy in patients with transfusion-dependent thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) throughout a 48 week treatment period. Participants who were either chelator-naïve, or who were previously treated with iron chelators (excluding deferasirox) for at least 6 months continuously, were eligible to participate in this study.

The study was divided into 2 phases:

1. Core Phase:

• Screening phase which lasted for a maximum of 4 weeks to determine patient eligibility followed by
• Period 1: Participants were treated with deferasirox DT from Baseline visit Day 1 to Week 24
• Period 2: Participants were treated with deferasirox FCT from Week 25 to Week 48:

At the discretion of the investigator, patients could switch from deferasirox DT to deferasirox FCT at any time during Period 1 of the Core phase, and vice versa, from deferasirox FCT to deferasirox DT at any time during Period 2 of the Core phase. Re-switching treatments was not allowed within each period.

2. Extension Phase:

Participants could continue deferasirox FCT formulation as per the judgment of the investigator, through an extension phase for a maximum of 48 weeks months from the last dose of deferasirox FCT received at the end of period 2 in the Core Phase or until one of the end of study criteria defined is met, whichever came first. Participation in the extension phase was optional.

The end of study was defined as the earliest occurrence of one of the following:

• The patient reached Week 96 in the Extension phase.
• Deferasirox FCT was locally reimbursed for this indication (only applicable for the Extension phase)
• Another clinical study or post-trial access program became available that could continue to provide deferasirox FCT in this patient population and all patients ongoing were eligible to be transferred to that clinical study.

Conditions

Transfusion-dependent Thalassemia; Non-transfusion-dependent Thalassemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Deferasirox DT followed by deferasirox FCT

Participants were treated with deferasirox DT followed by deferasirox FCT (core phase). Those who entered the extension phase were treated with deferasirox FCT

Group Type: EXPERIMENTAL

Deferasirox dispersable tablet (DT)

Intervention Type: DRUG

Deferasirox DT was provided as 125 mg, 250 mg, 500 mg dispersible tablets for oral use. The strengths provided in an individual country could differ and reflected the strengths available commercially in each country.

For iron chelation naive participants, the starting dose on Baseline Day 1 was 20 mg/kg/day in TDT and 10 mg/kg/day in NTDT.

For iron chelation (deferoxamine and/or deferiprone) pre-treated participants, the starting dose was equivalent to the dose of deferoxamine received (for participants pre-treated with deferoxamine) and based on their serum ferritin levels (for participants pre-treated with deferiprone).

Participants took deferasirox DT once daily for 24 weeks (core phase). The required number of deferasirox DT tablets were to be dispersed with gentle stirring in a glass of water.

Deferasirox film coated tablet (FCT)

Intervention Type: DRUG

Deferasirox FCT was provided as 90 mg, 180 mg, 360 mg film coated tablets for oral use. The FCT starting dose on Week 25 was 14 mg/kg/day in TDT and 7 mg/kg/day in NTDT.

Participants took deferasirox FCT once daily for 24 weeks during the core phase and up to 48 weeks during the extension phase. For patients with difficulties in swallowing deferasirox FCT, it was allowed to crush the film-coated tablets and administer the study drug by sprinkling the full dose on soft food (like yogurt or apple puree).

Interventions

Deferasirox dispersable tablet (DT)

Deferasirox DT was provided as 125 mg, 250 mg, 500 mg dispersible tablets for oral use. The strengths provided in an individual country could differ and reflected the strengths available commercially in each country.

For iron chelation naive participants, the starting dose on Baseline Day 1 was 20 mg/kg/day in TDT and 10 mg/kg/day in NTDT.

For iron chelation (deferoxamine and/or deferiprone) pre-treated participants, the starting dose was equivalent to the dose of deferoxamine received (for participants pre-treated with deferoxamine) and based on their serum ferritin levels (for participants pre-treated with deferiprone).

Participants took deferasirox DT once daily for 24 weeks (core phase). The required number of deferasirox DT tablets were to be dispersed with gentle stirring in a glass of water.

Intervention Type: DRUG

Deferasirox film coated tablet (FCT)

Deferasirox FCT was provided as 90 mg, 180 mg, 360 mg film coated tablets for oral use. The FCT starting dose on Week 25 was 14 mg/kg/day in TDT and 7 mg/kg/day in NTDT.

Participants took deferasirox FCT once daily for 24 weeks during the core phase and up to 48 weeks during the extension phase. For patients with difficulties in swallowing deferasirox FCT, it was allowed to crush the film-coated tablets and administer the study drug by sprinkling the full dose on soft food (like yogurt or apple puree).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Prior to any screening procedures were performed, written informed consent/assent must be provided. For pediatric patients, consent was obtained from parent(s) or legal patient's representative. Investigators also obtained assent of patients according to local, regional or national guidelines.

2. Male and female patient aged ≥ 2 years

3. Deferasirox naïve patient or chelated naive patient or treated by other chelators for at least 6 months, such as:

1. Deferiprone/ DFP

2. Deferoxamine /DFO

3. Combination (DFO + DFP)

4. Subject was willing to discontinue current iron chelation therapy at least 5 days prior to study day 1 and for the duration of the study

5. Patients with transfusion-dependent thalassemia (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of > 1000 ng/ml at screening and if available, LIC > 3 mg Fe/g dw within 6 months prior to screening

6. Patients with non-transfusion-dependent thalassemia with iron overload as shown by a serum ferritin level of ≥ 800 ng/ml at screening and if available, LIC ≥ 5 mg Fe/g dw within 6 months prior to screening

Exclusion Criteria

1. Creatinine clearance below the contraindication limit in the locally approved prescribing information.

2. Serum creatinine level > 1.5 x ULN (upper limit of normal)

3. AST (SGOT) /ALT (SGPT) > 5 x ULN, unless LIC confirmed as >10 mg Fe/dw within 6 months prior to screening visit.

4. Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void urine sample.

5. Patients with significant impaired gastrointestinal (GI) function or GI disease that might significantly alter the absorption of oral deferasirox (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).

6. Clinical or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive).

7. Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing any of the treatment options or patients unwilling or unable to comply with the protocol

8. Patients with a known history of HIV seropositivity (Elisa or Western blot).

9. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.

10. Patients participating in another clinical trial or receiving an investigational drug. Patients who have recently completed treatment with an investigational product must have ceased this treatment for at least five times the half-life of the investigational product.

11. History of hypersensitivity to any of the study drug or excipients.

12. Significant medical condition interfering with the ability to partake in this study (e.g. systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.).

13. 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

14. Women were considered post-menopausal and not of child bearing potential if they had had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or had had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow up hormone level assessment is she considered not of child bearing potential.

15. Sexually active males unless they used a condom during intercourse while taking drug and for 28 days after stopping study medication and should not father a child in this period. A condom was required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Novartis Investigative Site

Alexandria, , Egypt

Novartis Investigative Site

Cairo, , Egypt

Novartis Investigative Site

Zagazig, , Egypt

Novartis Investigative Site

Hazmiyeh, Beyrouth, Lebanon

Novartis Investigative Site

Rabat, , Morocco

Novartis Investigative Site

Al Ahsa, SAU, Saudi Arabia

Novartis Investigative Site

Jeddah, , Saudi Arabia

Novartis Investigative Site

Jeddah, , Saudi Arabia

Novartis Investigative Site

Riyadh, , Saudi Arabia

Novartis Investigative Site

Bangkok Noi, Bangkok, Thailand

Novartis Investigative Site

Bangkoknoi, Bangkok, Thailand

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Novartis Investigative Site

Antalya, , Turkey (Türkiye)

Novartis Investigative Site

Istanbul, , Turkey (Türkiye)

Novartis Investigative Site

Hanoi, , Vietnam

Novartis Investigative Site

Ho Chi Minh City, , Vietnam

Countries

Egypt; Lebanon; Morocco; Saudi Arabia; Thailand; Turkey (Türkiye); Vietnam

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-002282-61

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CICL670FIC05

Identifier Type: -

Identifier Source: org_study_id