Clinical trial NCT02993224: Open-label, Multicenter Study Assessing Preference for Deferasirox Film-coated Tablet Compared to Dispersible Tablet
Official title: Open-label, Multicenter, Single Arm, Phase II Study Assessing Treatment Patient Preference for New Deferasirox Formulation (Film-coated Tablet) Compared to the Reference Deferasirox Dispersible Tablet Formulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Transfusion-dependent Thalassemia
Non-transfusion-dependent Thalassemia
Keywords: thalassemia
TDT
transfusion-dependent
non-transfusion-dependent
NTDT
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-12-15
Enrollment: 148
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Number of Participants Preferring Deferasirox FCT or DT at Week 48 Based on Preference Questionnaire (Item 2)
timeFrame: Week 48
Secondary outcomes:
measure: Number of Participants Preferring Deferasirox FCT, Deferasirox DT or Previous Iron Chelation Therapy at Week 28 Based on Preference Questionnaire (Item 2)
timeFrame: Week 28
measure: Number of Participants Preferring Deferasirox DT or Previous Iron Chelation Therapy at Week 4 and Week 24 Based on Preference Questionnaire (Item 2)
timeFrame: Week 4 and Week 24
measure: Number of Participants Selecting Each Reason for Treatment Preference as Assessed by the Preference Questionnaire at Week 28 and Week 48
timeFrame: Week 28 and Week 48
measure: Percentage of Consumed Tablet Counts During Deferasirox DT and Deferasirox FCT Treatment Periods
timeFrame: Deferasirox DT: From Baseline up to Week 24. Deferasirox FCT: From Week 25 up to Week 48
measure: Change Over Time in Aftertaste Score of Palatability Questionnaire
timeFrame: Week 4, 24, 28 and 48
measure: Change Over Time in Palatability Score of Palatability Questionnaire
timeFrame: Week 4, 24, 28 and 48
measure: Change From Baseline in Adherence Domain Score of Modified Satisfaction With Iron Chelation (mSICT) Questionnaire
timeFrame: Baseline (week 2 or, if missing, week 3), week 24, 28 and 48
measure: Change From Baseline in Preference Domain Score of Modified Satisfaction With Iron Chelation (mSICT) Questionnaire
timeFrame: Baseline (week 2 or, if missing, week 3), week 24, 28 and 48
measure: Change From Baseline in Concerns Domain Score of Modified Satisfaction With Iron Chelation (mSICT) Questionnaire
timeFrame: Baseline (week 2 or, if missing, week 3), week 24, 28 and 48
measure: Change From Baseline in Gastrointestinal (GI) Symptom Score Based on GI Questionnaire
timeFrame: Baseline (week -1 or, if missing, week -2), week 24, 28 and 48
measure: Change From Baseline in Serum Ferritin Levels
timeFrame: From Baseline (Day 1) up to 96 weeks
Other outcomes:
Locations:
city: Alexandria
country: Egypt
facility: Novartis Investigative Site
city: Cairo
country: Egypt
facility: Novartis Investigative Site
city: Zagazig
country: Egypt
facility: Novartis Investigative Site
city: Hazmiyeh
country: Lebanon
facility: Novartis Investigative Site
state: Beirut
city: Rabat
country: Morocco
facility: Novartis Investigative Site
city: Al Ahsa
country: Saudi Arabia
facility: Novartis Investigative Site
state: SAU
city: Jeddah
country: Saudi Arabia
facility: Novartis Investigative Site
city: Jeddah
country: Saudi Arabia
facility: Novartis Investigative Site
city: Riyadh
country: Saudi Arabia
facility: Novartis Investigative Site
city: Bangkok noi
country: Thailand
facility: Novartis Investigative Site
state: Bangkok
city: Bangkoknoi
country: Thailand
facility: Novartis Investigative Site
state: Bangkok
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Antalya
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh City
country: Vietnam
facility: Novartis Investigative Site
Study officials:
References: