Back to resultsSafety Study of Crushed Deferasirox Film Coated Tablets in Pediatric Patients With Transfusional Hemosiderosis (MIMAS)
Primary Purpose
Iron Overload
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Deferasirox
Sponsored by
About this trial
This is an interventional treatment trial for Iron Overload focused on measuring Iron Chelation Therapy, Deferasirox, Asunra, Jadenu, Exjade, ICL 670, Pediatric
Eligibility Criteria
Key Inclusion Criteria:
- Patients ≥2 to <6 years old diagnosed with transfusional hemosiderosis
- Documented history of red blood cell transfusions
- Written informed consent/assent before any study-specific procedures. The consent will be obtained from caregiver(s) or patient's legal representative. Investigators will also obtain assent of patients according to local, regional, or national regulations.
- For patients on prior DFX: Serum ferritin (SF) >500 ng/mL, measured at screening visit 1 and requiring a DFX daily dose equivalent to FCT ≥ 7mg/kg/day.
- For patients on a prior chelator other than DFX (e.g. deferiprone or deferoxamine) or chelation naive: Serum ferritin (SF) >1000 ng/mL measured at screening visits 1 and 2.
Key Exclusion Criteria:
- Patients that receive more than one iron chelator at the same time as current iron chelation treatment. (Patients who have received combination therapy in their medical history but are currently being treated with a single ICT agent are eligible.)
- Patients continuing on deferoxamine or deferiprone in addition to study treatment. (Patients switching to or continuing on deferasirox are eligible).
- Unresolved adverse events if the patient was previously treated with deferiprone or deferoxamine or deferasirox.
- Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void sample urine measured at screening visit 1.
- Serum creatinine > age adjusted ULN measured at any screening visit
- Creatinine clearance below 90 mL/minute measured at any screening visit. Creatinine clearance using the Schwartz formula will be estimated from serum creatinine measured at each respective visit.
- ALT and/or AST > 2.5 x ULN measured at screening visit 1.
- Total bilirubin (TBIL) >1.5 x ULN measured at screening visit 1.
- Patients with significant impaired GI function or GI disease that may significantly alter the absorption of oral deferasirox FCT (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- History of and/or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive.
- Liver disease with severity of Child-Pugh Class B or C.
- History of hypersensitivity to any of the study drug or excipients.
- Patients participating in another clinical trial or receiving an investigational drug.
- Patients with a known history of HIV seropositivity.
- Patients unwilling or unable to comply with the protocol.
- 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.
- Significant medical condition interfering with the ability to partake in this study (e.g. uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease: cardiovascular, renal, hepatic, etc.).
- Female patients who reach menarche and they or their caregivers refuse pregnancy testing and/or if there is a positive pregnancy test result.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Deferasirox
Arm Description
Crushed deferasirox (ICL670) FCT for oral use daily. Deferasirox FCT dosing was based on subject's weight.
Outcomes
Primary Outcome Measures
Number of Participants With Selected Gastrointestinal Disorders up to 24 Weeks
To assess the safety of crushed deferasirox FCT with respect to selected gastrointestinal (GI) disorders (esophagitis, stomatitis, mouth ulceration, gastric ulcers, haemorrhage, abdominal pain, diarrhea, nausea, and vomiting). Only descriptive analysis performed.
Secondary Outcome Measures
Adverse Events Profile
Analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event TEAEs and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.
Number of Participants With Notable Changes in ECG Values From Baseline
Safety measured by the notable post-baseline changes in ECG values (PR, QRS, QT, QTcF and HR intervals) compared to baseline. Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Absolute Change From Baseline in Serum Ferritin (SF)
Absolute change from baseline over time in SF values up to 24 weeks of treatment were to be provided. Only descriptive analysis performed.
Number of Participants With Worst Post-baseline Values in Selected Chemistry Parameters
Safety measured by the worst post-baseline severity grade observed in a patient calculated using the normal/low/high classifications based on local laboratory normal ranges, regardless of the baseline status. Baseline was defined as the last non-missing value on or prior to the first dose. The selected chemistry parameters were: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), total bilirubin, direct bilirubin, serum creatinine and Urine protein creatinine ratio (UPCR) (Protein/Creatinine represented UPCR). Only descriptive analysis performed.
Number of Participants With Clinically Significant Auditory Assessments Changes From Baseline
Safety measured by notable post-baseline changes in Auditory assessments (comprehensive audiometry threshold examination and speech recognition). Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Number of Participants With Clinically Significant Ocular Assessments Changes From Baseline
Safety measured by notable post-baseline changes in Ocular assessments (Distance visual acuity test, Applanation tonometry, lens photography, wide angle fundus photography of the retina and optic nerve). Ocular assessment were required at screening and end of Treatment; during treatment, they were to be performed at the discretion of the investigator based on patient reporting symptoms. Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Absolute Change From Baseline in Systolic and Diastolic Blood Pressures (mmHg)
Absolute change from baseline over time in systolic and diastolic blood pressures measurements were to be provided. Only descriptive analysis performed.
Absolute Change From Baseline in Pulse Rate (Bpm)
Absolute change from baseline over time in supine pulse rate was to be provided. Only descriptive analysis performed.
Absolute Change From Baseline in Body Temperature (°C)
Absolute change from baseline over time in body temperature measurements was to be provided. Only descriptive analysis performed.
Absolute Change From Baseline in Body Weight (kg)
Absolute change from baseline over time in body weight measurements was to be provided. Only descriptive analysis performed.
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Participants Pre-treated With Deferasirox: Mean Change From Baseline in Adherence
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT adherence domain consisted of 6 items from the child's perspective and 6 items from the caregiver's perspective, each with a possible score of 1 to 5, for an overall possible score range of 6 to 30. A higher score indicates poorer adherence. Only descriptive analysis performed.
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Type of Medicine Child Like Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the type of medicine the child said he/she liked best (tablet to dissolve in liquid, tablet (taken once a day), tablet (taken 3 times a day), tablet crushed, sprinkle powder on food, injection and I don't know). These items were presented descriptively using frequency counts.
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Reasons Child Preferred Crushed Medicine Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the reason child preferred crushed medicine (taste, aftertaste, convenience, number of pills, no/less side effects, can correctly prepare the medicine, easier to remember to take the medicine, number of times he/she has to take the medicine, no/less pain on the injection site, gain personal time with their family and friends, and other). These items were presented descriptively using frequency counts.
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Rank Based on Child's Preference Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the rank of the medicine (tablet to dissolve in liquid, tablet taken once a day, tablet taken 3 times a day, tablet crushed, sprinkle powder on food and injection), with a range of 1 to 6 (1 being most preferred and 6 being least preferred), based on what the child prefers. These items were presented descriptively using frequency count.
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Participants Pre-treated With Deferasirox: Mean Change From Baseline in Concerns
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT concerns domain scale for child's response had a possible range from 2 to 10, based on two questions and the mSICT concerns domain scale for caregiver's responses had the possible range of 1 to 5 based on one question. A higher score indicated fewer concerns. Only descriptive analysis performed.
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Mean Change From Baseline in Adherence
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT adherence domain consisted of 6 items from the child's perspective and 6 items from the caregiver's perspective, each with a possible score of 1 to 5, for an overall possible score range of 6 to 30. A higher score indicates poorer adherence. Only descriptive analysis performed.
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Type of Medicine Child Like Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the type of medicine the child said he/she liked best (tablet to dissolve in liquid, tablet (taken once a day), tablet (taken 3 times a day), tablet crushed, sprinkle powder on food, injection and I don't know). These items were presented descriptively using frequency counts.
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Reasons Child Preferred Crushed Medicine Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the reason child preferred crushed medicine (taste, aftertaste, convenience, number of pills, no/less side effects, can correctly prepare the medicine, easier to remember to take the medicine, number of times he/she has to take the medicine, no/less pain on the injection site, gain personal time with their family and friends, and other). These items were presented descriptively using frequency counts.
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Rank Based on Child's Preference Scoring
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the rank of the medicine (tablet to dissolve in liquid, tablet taken once a day, tablet taken 3 times a day, tablet crushed, sprinkle powder on food and injection), with a range of 1 to 6 (1 being most preferred and 6 being least preferred), based on what the child prefers. These items were presented descriptively using frequency counts.
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Mean Change From Baseline in Concerns
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT concerns domain scale for child's response had a possible range from 2 to 10, based on two questions and the mSICT concerns domain scale for caregiver's responses had the possible range of 1 to 5 based on one question. A higher score indicated fewer concerns. Only descriptive analysis performed.
Palatability Score in Chelation Naive Participants
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated separately. Among the taste items, first one measured taste on a five point response scale. The last two items measured what happened after taking the medicine, i.e., swallowed or vomited etc. and how the perceived amount of liquid taken with the medicine was, enough, not enough or too much. The palatability summary score was calculated from these three items using a scoring matrix and the score ranges from 0 to 11. A higher score indicates better palatability. Only descriptive analysis was performed.
Number of Chelation Naive Participants With Palatability After Taste Item Scoring
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated as a separate item and scored on a 5-point response scale with the response format Very good = 1 (best), Good = 2, Neither good nor bad = 3, Bad = 4, Very bad = 5 (worst). Only descriptive analysis performed using frequency counts.
Palatability Score in Participants Pre-treated With Deferasirox
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated separately. Among the taste items, first one measured taste on a five point response scale. The last two items measured what happened after taking the medicine, i.e., swallowed or vomited etc. and how the perceived amount of liquid taken with the medicine was, enough, not enough or too much. The palatability summary score was calculated from these three items using a scoring matrix and the score ranges from 0 to 11. A higher score indicates better palatability. Only descriptive analysis was performed.
Number of Participants Pre-treated With Deferasirox With Palatability After Taste Item Scoring
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated as a separate item and scored on a 5-point response scale with the response format Very good = 1 (best), Good = 2, Neither good nor bad = 3, Bad = 4, Very bad = 5 (worst). Only descriptive analysis performed using frequency counts.
GI Symptom Score in Chelation Naive Participants
The GI symptom score was calculated from responses to 5 questions, each with a possible score of 1 to 5, for an overall possible score range of 5 to 25, where a lower score represents a less severe GI symptom and a higher score represents a more severe GI symptom. GI symptom scores were summarized using descriptive statistics at week 2, week 3, week 4, week 8, week 12, week 16, week 20 and EOT.
Number of Participants With GI Bowel Movements Item Scoring in Chelation Naive Participants
The GI symptom questionnaire consisted of 6 items, 5 of which were scored using a 1-5 rating scale. The sixth item assessed bowel movement frequency during the past week, using 7 response options 0 = 0 ("None"), 1 = 1, 2 = 2, 3 = 3, 4 = 4, 5 = "5 - 10" and 6 = "11 or more". The GI bowel movements item score was presented descriptively using frequency counts.
GI Symptom Score in Participants Pre-treated With Deferasirox
The GI symptom score was calculated from responses to 5 questions, each with a possible score of 1 to 5, for an overall possible score range of 5 to 25, where a lower score represents a less severe GI symptom and a higher score represents a more severe GI symptom. GI symptom scores were summarized using descriptive statistics at week 2, week 3, week 4, week 8, week 12, week 16, week 20 and EOT.
Number of Participants With GI Bowel Movements Item Scoring in Participants Pre-treated With Deferasirox
The GI symptom questionnaire consisted of 6 items, 5 of which were scored using a 1-5 rating scale. The sixth item assessed bowel movement frequency during the past week, using 7 response options 0 = 0 ("None"), 1 = 1, 2 = 2, 3 = 3, 4 = 4, 5 = "5 - 10" and 6 = "11 or more". The GI bowel movements item score was presented descriptively using frequency counts.
Full Information
NCT ID
NCT03372083
First Posted
November 21, 2017
Last Updated
August 24, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03372083
Brief Title
Safety Study of Crushed Deferasirox Film Coated Tablets in Pediatric Patients With Transfusional Hemosiderosis
Acronym
MIMAS
Official Title
A Single-arm Interventional Phase IV, Post-authorisation Study Evaluating the Safety of Pediatric Patients With Transfusional Hemosiderosis Treated With Deferasirox Crushed Film Coated Tablets
Study Type
Interventional
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
January 16, 2018 (Actual)
Primary Completion Date
December 5, 2019 (Actual)
Study Completion Date
December 5, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study employed a prospective, single-arm, global multi-center interventional open-label, non-randomized design to identify and assess safety profile of the crushed deferasirox FCT when administered up to 24 weeks in pediatric patients aged ≥2 to <6 years with transfusional hemosiderosis. The study was designed to enroll a minimum of 40 patients. Forty-four patients were treated and analyzed.
Detailed Description
The study included a screening period (from Day 0-14) with two visits at least 7 days apart to assess eligibility of patients that were chelation naïve or on a prior iron chelator treatment other than DFX. For Patients on DFX treatment prior to study entry only one screening visit (screening visit 1) were to occur to determine eligibility. Any current chelation therapy except deferasirox were to be discontinued to undergo a 5-day washout period prior to commencing a 24 week treatment period with crushed deferasirox FCT.
All patients were to have weekly visits for the first month to monitor renal function. Hepatic function were to be assessed biweekly during the first month. Thereafter, monthly safety assessments were to be performed, including the monitoring of serum ferritin values and trends in order to adapt patient treatment.
Eligibility, application of dosing standards and adjustments, as well as safety and serum ferritin assessments as specified in the protocol.
The planned duration of treatment was 24 weeks followed by a 30-day safety follow up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Iron Overload
Keywords
Iron Chelation Therapy, Deferasirox, Asunra, Jadenu, Exjade, ICL 670, Pediatric
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Deferasirox
Arm Type
Experimental
Arm Description
Crushed deferasirox (ICL670) FCT for oral use daily. Deferasirox FCT dosing was based on subject's weight.
Intervention Type
Drug
Intervention Name(s)
Deferasirox
Other Intervention Name(s)
ICL670
Intervention Description
Deferosirox was provided in tablet forms of 90, 180 and 360mg. Tablets were crushed in the home environment and administered by sprinkling the full dose on to soft food to be consumed immediately.
Primary Outcome Measure Information:
Title
Number of Participants With Selected Gastrointestinal Disorders up to 24 Weeks
Description
To assess the safety of crushed deferasirox FCT with respect to selected gastrointestinal (GI) disorders (esophagitis, stomatitis, mouth ulceration, gastric ulcers, haemorrhage, abdominal pain, diarrhea, nausea, and vomiting). Only descriptive analysis performed.
Time Frame
Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Secondary Outcome Measure Information:
Title
Adverse Events Profile
Description
Analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event TEAEs and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.
Time Frame
Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Title
Number of Participants With Notable Changes in ECG Values From Baseline
Description
Safety measured by the notable post-baseline changes in ECG values (PR, QRS, QT, QTcF and HR intervals) compared to baseline. Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Time Frame
Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Title
Absolute Change From Baseline in Serum Ferritin (SF)
Description
Absolute change from baseline over time in SF values up to 24 weeks of treatment were to be provided. Only descriptive analysis performed.
Time Frame
Baseline (BL), Week 4, Week 8, Week 12, Week 16, EOT (Week 24)
Title
Number of Participants With Worst Post-baseline Values in Selected Chemistry Parameters
Description
Safety measured by the worst post-baseline severity grade observed in a patient calculated using the normal/low/high classifications based on local laboratory normal ranges, regardless of the baseline status. Baseline was defined as the last non-missing value on or prior to the first dose. The selected chemistry parameters were: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST), total bilirubin, direct bilirubin, serum creatinine and Urine protein creatinine ratio (UPCR) (Protein/Creatinine represented UPCR). Only descriptive analysis performed.
Time Frame
Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Title
Number of Participants With Clinically Significant Auditory Assessments Changes From Baseline
Description
Safety measured by notable post-baseline changes in Auditory assessments (comprehensive audiometry threshold examination and speech recognition). Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Time Frame
Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Title
Number of Participants With Clinically Significant Ocular Assessments Changes From Baseline
Description
Safety measured by notable post-baseline changes in Ocular assessments (Distance visual acuity test, Applanation tonometry, lens photography, wide angle fundus photography of the retina and optic nerve). Ocular assessment were required at screening and end of Treatment; during treatment, they were to be performed at the discretion of the investigator based on patient reporting symptoms. Baseline was defined as the last non-missing value on or prior to the first dose. Only descriptive analysis performed.
Time Frame
Baseline (Week 1 Day 1) up to Week 24, plus 30 day safety follow-up.
Title
Absolute Change From Baseline in Systolic and Diastolic Blood Pressures (mmHg)
Description
Absolute change from baseline over time in systolic and diastolic blood pressures measurements were to be provided. Only descriptive analysis performed.
Time Frame
Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Title
Absolute Change From Baseline in Pulse Rate (Bpm)
Description
Absolute change from baseline over time in supine pulse rate was to be provided. Only descriptive analysis performed.
Time Frame
Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Title
Absolute Change From Baseline in Body Temperature (°C)
Description
Absolute change from baseline over time in body temperature measurements was to be provided. Only descriptive analysis performed.
Time Frame
Baseline (BL), Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Title
Absolute Change From Baseline in Body Weight (kg)
Description
Absolute change from baseline over time in body weight measurements was to be provided. Only descriptive analysis performed.
Time Frame
Baseline (BL), Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Title
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Participants Pre-treated With Deferasirox: Mean Change From Baseline in Adherence
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT adherence domain consisted of 6 items from the child's perspective and 6 items from the caregiver's perspective, each with a possible score of 1 to 5, for an overall possible score range of 6 to 30. A higher score indicates poorer adherence. Only descriptive analysis performed.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Type of Medicine Child Like Scoring
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the type of medicine the child said he/she liked best (tablet to dissolve in liquid, tablet (taken once a day), tablet (taken 3 times a day), tablet crushed, sprinkle powder on food, injection and I don't know). These items were presented descriptively using frequency counts.
Time Frame
Baseline (BL), Week 4, Week 12, EOT (Week 24)
Title
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Reasons Child Preferred Crushed Medicine Scoring
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the reason child preferred crushed medicine (taste, aftertaste, convenience, number of pills, no/less side effects, can correctly prepare the medicine, easier to remember to take the medicine, number of times he/she has to take the medicine, no/less pain on the injection site, gain personal time with their family and friends, and other). These items were presented descriptively using frequency counts.
Time Frame
Baseline (BL), Week 4, Week 12, EOT (Week 24)
Title
Modified SICT in Participants Pre-treated With Deferasirox: Number of Participants With Rank Based on Child's Preference Scoring
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the rank of the medicine (tablet to dissolve in liquid, tablet taken once a day, tablet taken 3 times a day, tablet crushed, sprinkle powder on food and injection), with a range of 1 to 6 (1 being most preferred and 6 being least preferred), based on what the child prefers. These items were presented descriptively using frequency count.
Time Frame
Baseline (BL), Week 4, Week 12, EOT (Week 24)
Title
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Participants Pre-treated With Deferasirox: Mean Change From Baseline in Concerns
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT concerns domain scale for child's response had a possible range from 2 to 10, based on two questions and the mSICT concerns domain scale for caregiver's responses had the possible range of 1 to 5 based on one question. A higher score indicated fewer concerns. Only descriptive analysis performed.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Mean Change From Baseline in Adherence
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT adherence domain consisted of 6 items from the child's perspective and 6 items from the caregiver's perspective, each with a possible score of 1 to 5, for an overall possible score range of 6 to 30. A higher score indicates poorer adherence. Only descriptive analysis performed.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Type of Medicine Child Like Scoring
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the type of medicine the child said he/she liked best (tablet to dissolve in liquid, tablet (taken once a day), tablet (taken 3 times a day), tablet crushed, sprinkle powder on food, injection and I don't know). These items were presented descriptively using frequency counts.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Reasons Child Preferred Crushed Medicine Scoring
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the reason child preferred crushed medicine (taste, aftertaste, convenience, number of pills, no/less side effects, can correctly prepare the medicine, easier to remember to take the medicine, number of times he/she has to take the medicine, no/less pain on the injection site, gain personal time with their family and friends, and other). These items were presented descriptively using frequency counts.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Number of Participants With Rank Based on Child's Preference Scoring
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT preference domain consisted of 3 items including the rank of the medicine (tablet to dissolve in liquid, tablet taken once a day, tablet taken 3 times a day, tablet crushed, sprinkle powder on food and injection), with a range of 1 to 6 (1 being most preferred and 6 being least preferred), based on what the child prefers. These items were presented descriptively using frequency counts.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Modified Satisfaction With Iron Chelation Therapy (Modified SICT) in Chelation Naive Participants: Mean Change From Baseline in Concerns
Description
The mSICT questionnaire was to be completed at screening visit 1, week 4, week 12 and EOT. The responses from screening visit 1 for mSICT questionnaire were to be considered as baseline. The modified SICT consisted of 20 items that represented 3 domains: Adherence, Preference and Concerns. The mSICT concerns domain scale for child's response had a possible range from 2 to 10, based on two questions and the mSICT concerns domain scale for caregiver's responses had the possible range of 1 to 5 based on one question. A higher score indicated fewer concerns. Only descriptive analysis performed.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Palatability Score in Chelation Naive Participants
Description
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated separately. Among the taste items, first one measured taste on a five point response scale. The last two items measured what happened after taking the medicine, i.e., swallowed or vomited etc. and how the perceived amount of liquid taken with the medicine was, enough, not enough or too much. The palatability summary score was calculated from these three items using a scoring matrix and the score ranges from 0 to 11. A higher score indicates better palatability. Only descriptive analysis was performed.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Number of Chelation Naive Participants With Palatability After Taste Item Scoring
Description
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated as a separate item and scored on a 5-point response scale with the response format Very good = 1 (best), Good = 2, Neither good nor bad = 3, Bad = 4, Very bad = 5 (worst). Only descriptive analysis performed using frequency counts.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Palatability Score in Participants Pre-treated With Deferasirox
Description
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated separately. Among the taste items, first one measured taste on a five point response scale. The last two items measured what happened after taking the medicine, i.e., swallowed or vomited etc. and how the perceived amount of liquid taken with the medicine was, enough, not enough or too much. The palatability summary score was calculated from these three items using a scoring matrix and the score ranges from 0 to 11. A higher score indicates better palatability. Only descriptive analysis was performed.
Time Frame
Week 4, Week 12, EOT (Week 24)
Title
Number of Participants Pre-treated With Deferasirox With Palatability After Taste Item Scoring
Description
The palatability (taste and ability to consume medicine) questionnaire consisted of 4 items, three items measuring taste or ability to consume medicine and one item measuring aftertaste. The aftertaste item was treated as a separate item and scored on a 5-point response scale with the response format Very good = 1 (best), Good = 2, Neither good nor bad = 3, Bad = 4, Very bad = 5 (worst). Only descriptive analysis performed using frequency counts.
Time Frame
Baseline, Week 4, Week 12, EOT (Week 24)
Title
GI Symptom Score in Chelation Naive Participants
Description
The GI symptom score was calculated from responses to 5 questions, each with a possible score of 1 to 5, for an overall possible score range of 5 to 25, where a lower score represents a less severe GI symptom and a higher score represents a more severe GI symptom. GI symptom scores were summarized using descriptive statistics at week 2, week 3, week 4, week 8, week 12, week 16, week 20 and EOT.
Time Frame
Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Title
Number of Participants With GI Bowel Movements Item Scoring in Chelation Naive Participants
Description
The GI symptom questionnaire consisted of 6 items, 5 of which were scored using a 1-5 rating scale. The sixth item assessed bowel movement frequency during the past week, using 7 response options 0 = 0 ("None"), 1 = 1, 2 = 2, 3 = 3, 4 = 4, 5 = "5 - 10" and 6 = "11 or more". The GI bowel movements item score was presented descriptively using frequency counts.
Time Frame
Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Title
GI Symptom Score in Participants Pre-treated With Deferasirox
Description
The GI symptom score was calculated from responses to 5 questions, each with a possible score of 1 to 5, for an overall possible score range of 5 to 25, where a lower score represents a less severe GI symptom and a higher score represents a more severe GI symptom. GI symptom scores were summarized using descriptive statistics at week 2, week 3, week 4, week 8, week 12, week 16, week 20 and EOT.
Time Frame
Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
Title
Number of Participants With GI Bowel Movements Item Scoring in Participants Pre-treated With Deferasirox
Description
The GI symptom questionnaire consisted of 6 items, 5 of which were scored using a 1-5 rating scale. The sixth item assessed bowel movement frequency during the past week, using 7 response options 0 = 0 ("None"), 1 = 1, 2 = 2, 3 = 3, 4 = 4, 5 = "5 - 10" and 6 = "11 or more". The GI bowel movements item score was presented descriptively using frequency counts.
Time Frame
Baseline, Week 2, Week 3, Week 4, Week 8, Week 12, Week 16, Week 20, EOT (Week 24)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Patients ≥2 to <6 years old diagnosed with transfusional hemosiderosis
Documented history of red blood cell transfusions
Written informed consent/assent before any study-specific procedures. The consent will be obtained from caregiver(s) or patient's legal representative. Investigators will also obtain assent of patients according to local, regional, or national regulations.
For patients on prior DFX: Serum ferritin (SF) >500 ng/mL, measured at screening visit 1 and requiring a DFX daily dose equivalent to FCT ≥ 7mg/kg/day.
For patients on a prior chelator other than DFX (e.g. deferiprone or deferoxamine) or chelation naive: Serum ferritin (SF) >1000 ng/mL measured at screening visits 1 and 2.
Key Exclusion Criteria:
Patients that receive more than one iron chelator at the same time as current iron chelation treatment. (Patients who have received combination therapy in their medical history but are currently being treated with a single ICT agent are eligible.)
Patients continuing on deferoxamine or deferiprone in addition to study treatment. (Patients switching to or continuing on deferasirox are eligible).
Unresolved adverse events if the patient was previously treated with deferiprone or deferoxamine or deferasirox.
Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 mg/mg in a non-first void sample urine measured at screening visit 1.
Serum creatinine > age adjusted ULN measured at any screening visit
Creatinine clearance below 90 mL/minute measured at any screening visit. Creatinine clearance using the Schwartz formula will be estimated from serum creatinine measured at each respective visit.
ALT and/or AST > 2.5 x ULN measured at screening visit 1.
Total bilirubin (TBIL) >1.5 x ULN measured at screening visit 1.
Patients with significant impaired GI function or GI disease that may significantly alter the absorption of oral deferasirox FCT (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
History of and/or laboratory evidence of active Hepatitis B or Hepatitis C (HBsAg in the absence of HBsAb OR HCV Ab positive with HCV RNA positive.
Liver disease with severity of Child-Pugh Class B or C.
History of hypersensitivity to any of the study drug or excipients.
Patients participating in another clinical trial or receiving an investigational drug.
Patients with a known history of HIV seropositivity.
Patients unwilling or unable to comply with the protocol.
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.
Significant medical condition interfering with the ability to partake in this study (e.g. uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease: cardiovascular, renal, hepatic, etc.).
Female patients who reach menarche and they or their caregivers refuse pregnancy testing and/or if there is a positive pregnancy test result.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Zagazig
ZIP/Postal Code
44519
Country
Egypt
Facility Name
Novartis Investigative Site
City
Cona
State/Province
FE
ZIP/Postal Code
44100
Country
Italy
Facility Name
Novartis Investigative Site
City
Cagliari
State/Province
ITA
ZIP/Postal Code
09121
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80138
Country
Italy
Facility Name
Novartis Investigative Site
City
Hazmiyeh
State/Province
Beirut
ZIP/Postal Code
PO BOX 213
Country
Lebanon
Facility Name
Novartis Investigative Site
City
Muscat
ZIP/Postal Code
123
Country
Oman
Facility Name
Novartis Investigative Site
City
Bangkok noi
State/Province
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Novartis Investigative Site
City
Muang
State/Province
Chiangmai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
Novartis Investigative Site
City
Dubai
ZIP/Postal Code
9115
Country
United Arab Emirates
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
Safety Study of Crushed Deferasirox Film Coated Tablets in Pediatric Patients With Transfusional Hemosiderosis
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